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Sample records for neonatal rat mandibular

  1. Mandibular distraction in neonates: indications, technique, results

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    Sesenna Enrico

    2012-02-01

    Full Text Available Abstract Background The Pierre Robin Sequence features were first described by Robin in 1923 and include micrognathia, glossoptosis and respiratory distress with an incidence estimated as 1:8,500 to 1:20,000 newborns. Upper airway obstruction and feeding difficulties are the main concerns related to the pathology. Mandibular distraction should be considered a treatment option (when other treatments result inadequate. Patiants and methods Ten patients between the ages of 1 month and 2 years with severe micrognathia and airway obstruction were treated with Mandibular Distraction Osteogenesis (MDO. All patients underwent fibroscopic examination of the upper airway and a radiographic imaging and/or computed tomography scans to detect malformations and to confirm that the obstruction was caused by posterior tongue displacement. All patients were evaluated by a multidisciplinary team. Indications for surgery included frequent apneic episodes with severe desaturation (70%. Gavage therapy was employed in all patients since oral feeding was not possible. The two tracheotomy patients were 5 months and 2 years old respectively, and the distraction procedure was performed to remove the tracheotomy tube. All patients were treated with bilateral mandibular distraction: two cases with an external multivector distraction device, six cases with an internal non-resorbable device and two cases with an internal resorbable device. In one case, the patient with Goldenhar's Syndrome, the procedure was repeated. Results The resolution of symptoms was obtained in all patients, and, when present, tracheotomy was removed without complications. Of the two patients with pre-existing tracheotomies, in the younger patient (5 months old the tracheotomy was removed 7 days postoperatively. In the Goldenhar's syndrome case (2 years old a Montgomery device was necessary for 6 months due to the presence of tracheotomy-inducted tracheomalacia. Patients were discharged when the

  2. Effects of mandibular advancement plus prohibition of lower incisor movement on mandibular growth in rats.

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    Taira, Koji; Iino, Shoichiro; Kubota, Takeshi; Fukunaga, Tomohiro; Miyawaki, Shouichi

    2009-11-01

    To test the hypothesis that mandibular advancement with the use of a fixed functional appliance combined with prohibition of labial movement of the lower incisors will have no effect on mandibular growth in growing rats. Fifteen 4-week-old male rats were divided into fixed, unfixed, and control groups (n = 5, each). Bite-jumping appliances were used in the fixed and unfixed groups. Sites of bone perforation and the lower incisors were connected with ligature wires in the fixed group. The ramus height, mandibular length, and inclination of lower incisors were examined for 4 weeks, and those values were compared among five intervals and three groups by through one-way analysis of variance models and the Bonferroni multiple comparison test for post hoc comparison. Increases in ramus height and mandibular length during the experimental period were 1.5 mm and 2.5 mm in the fixed group, 1 mm and 1.5 mm in the unfixed group, and 1.2 mm and 1.9 mm in the control group, respectively. Growth of ramus height and growth of mandibular length in the fixed group were greater than in the unfixed and control groups during the experimental period. The inclination of lower incisors in the unfixed group was increased 8.0 degrees throughout the experimental period, which differed from results obtained in the other groups. Mandibular growth was accelerated effectively before and during the pubertal period in rats by mandibular advancement with a fixed functional appliance combined with prohibition of labial movement of the lower incisor.

  3. Neonatal mandibular distraction osteogenesis: converting virtual surgical planning into an operative reality.

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    Doscher, Matthew E; Garfein, Evan S; Bent, John; Tepper, Oren M

    2014-02-01

    Mandibular distraction osteogenesis (DO) has become an accepted method to manage severe cases of micrognathia-induced airway obstruction in neonates. Current imaging used to plan these procedures aids in surgical planning, but offers only a rough guide for the operating room. To our knowledge the following report offers the first description of virtual surgery used to guide DO in the mandible of a neonate. The plan provided a valuable link between the simulated procedure and the actual operative steps. Such technology can serve an important role in DO and offers objective guidance in device selection, vector planning and operative guide positioning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Trabecular organization in mandibular osteodistraction in growing and maturing rats.

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    Shin, Ja Young; Liu, Zi Jun; King, Gregory Joseph

    2005-01-01

    Our goal was to investigate the trabecular organization of the distraction regenerate during various consolidation phases and as a result of various distraction rates. One hundred ninety-two growing and maturing rats (96 each) received unilateral mandibular osteotomies and distraction device placement. They were randomly allocated into 4 distraction rate groups (0, 0.2, 0.4, and 0.6 mm/day for 5 days) after a 3-day latency. Eight rats from each rate group were sacrificed at early (10 days), mid (24 days) and late (38 days) consolidation time points. Harvested hemimandibles were embedded in micro-bed resin, sectioned sagittally at 10 mum thickness and stained using the Von Kossa method. The histologic images were captured and processed using Adobe Photoshop (Version 7.0; Adobe Systems Inc, San Jose, CA). Custom-made software (MacAzimuth; written by Prof. J.M. Rensberger, University of Washington) was further used to analyze the orientation (anisotropy and angle distribution) and mass (density and thickness) of trabecular structures in the regenerates. Trabecular orientation significantly differed at the mid-consolidation time point with less anisotropy ( P consolidation ( P time points ( P bone mineral density and microdensity ( P consolidation with a greater increase in trabecular mass. Growing rats showed a greater capacity for trabecular organization at earlier time points. However, distraction rate did not have an effect on trabecular organization. These results suggest that trabecular organization can be used as an important indicator to evaluate bone maturation and quality in the distraction regenerate.

  5. Cerebral microbleeds in a neonatal rat model.

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    Brianna Carusillo Theriault

    Full Text Available In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter.Pregnant Wistar rats were subjected to intrauterine ischemia (IUI and low-dose maternal lipopolysaccharide (mLPS at embryonic day (E 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks.mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2 and protein (CD31, MMP2, MMP9 for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls.In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.

  6. Transoral intratracheal inoculation method for use with neonatal rats.

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    Martínez-Burnes, J; López, A; Lemke, K; Dobbin, G

    2001-04-01

    Studying the effects of toxic and infective compounds on the respiratory system requires a reliable method for delivering inoculum into the distal region of the lung. Although transoral intratracheal inoculation methods have been well documented for adult rats, to the authors' knowledge, a reliable method has not been validated for neonatal rats. The purpose of the study reported here was to develop a simple method for transoral inoculation in rat neonates. Seven-day-old Fischer 344 rats were anesthetized with halothane, and a spinal needle was inserted in the tracheal lumen, by use of illumination and a modified otoscope. Meconium was injected into the lungs as a marker, and the neonates were kept under close observation. After euthanasia at 24 h, lungs were removed and fixed in formalin, and the microscopic distribution of the inoculum was assessed in the left, right cranial, middle, median, and caudal lung lobes. Microscopic examination of lungs indicated that intratracheal inoculation was achieved in 100% of neonatal lungs and the inoculum was consistently distributed in the alveoli of all pulmonary lobes. Important complications or mortality were not observed in the neonates. Intratracheal inoculation of neonatal rats is possible by use of a modified otoscope for transoral illumination. This technique is simple and reproducible and ensures, without complications, widespread distribution of inoculum in the lungs of neonatal rats.

  7. Three-dimensional analysis of morphological changes of rat mandibular head induced by administration of adjuvant in mandibular joint cavity

    International Nuclear Information System (INIS)

    Kuroki, Yosuke

    2008-01-01

    Temporal morphological changes of human osteoarthritis (OA) related to temporomandibular joint dysfunction (TMJ) are unknown because of lack of the animal model. The author made the model as in the title. Complete Freud's adjuvant (CFA) was injected in the mandibular joint cavity of male standard deviation (SD) rats with monitoring by X-ray. The site of injection was determined previously with the machine RmCT (in vivo 3D micro-X-ray CT for laboratory animals, Rigaku Corp.), which consisted of rotatable X-ray tube and facing flat panel detector, at whose center anesthetized rat was placed. The machine was also used for observation of the mandible just and 1-14 days after CFA injection and images were processed to 2D and 3D with the software I-view-R (Rigaku Corp.). Morphological changes were seen at 7-14 days on the CT images, and pathologically at 14 days, erosion or osteophytosis in 9/12 animals and enlargement of mandibular head. The cavity treated became larger for 1-14 days persistently. These results indicated that morphological changes accompanying the chronic inflammation had occurred, which was thought useful as a model of TMJ-OA. (R.T.)

  8. Effects of the masticatory demand on the rat mandibular development

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    Hichijo, N.; Kawai, N.; Mori, H.; Sano, R.; Ohnuki, Y.; Okumura, S.; Langenbach, G.E.J.; Tanaka, E.

    2014-01-01

    The influence of masticatory loading stimulus on mandibular development is not fully clear. In this paper, experimental alterations in the daily muscle use, caused by a changed diet consistency, were continuously monitored, while adaptations in bone and cartilage were examined. It is hypothesised

  9. Neonatal paracetamol treatment reduces long-term nociceptive behaviour after neonatal procedural pain in rats.

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    van den Hoogen, N J; Tibboel, D; Honig, W M M; Hermes, D; Patijn, J; Joosten, E A

    2016-09-01

    Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain. A repetitive needle-prick model was used, in which neonatal rats received four needle pricks into the left hind paw per day from postnatal day 0 to day 7 (P0-P7). Paracetamol (50 mg/kg/day s.c.) was administered daily (P0-P7), and sensitivity to mechanical stimuli was compared with a needle-prick/saline-treated group and to a tactile control group. At 8 weeks of age, all animals underwent an ipsilateral paw-incision, modelling postoperative pain, and the duration of hypersensitivity was assessed. Neonatal paracetamol administration had no effect upon short-term mechanical hypersensitivity during the first postnatal week or upon long-term baseline sensitivity from 3 to 8 weeks. However, neonatal paracetamol administration significantly reduced the postoperative mechanical hypersensitivity in young adults, caused by repetitive needle pricking. Paracetamol administration during neonatal procedural pain does not alter short-term or long-term effects on mechanical sensitivity, but does reduce the duration of increased postoperative mechanical hypersensitivity in a clinically relevant neonatal procedural pain model. Paracetamol can be used safely in neonatal rats. Neonatal paracetamol treatment had no effect upon short-term mechanical hypersensitivity during the first postnatal week, nor upon long-term baseline sensitivity from 3 to 8 weeks. Paracetamol treatment during the first postnatal week significantly reduced the postoperative mechanical hypersensitivity in young adult rats. © 2016 European Pain Federation

  10. The neurological effects of brevetoxin on neonatal rats

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    Tapley, S.R.; Ramsdell, J.S.; Xi, D. [Medical Univ. of South Carolina, Charleston, SC (United States)] [and others

    1994-12-31

    We have investigated the neuroexcitatory and neurodegenerative effects of brevetoxin on neonatal rats. Brevetoxin, a marine-biotoxin that has been implicated in several seafood poisoning incidents, is produced by the dinoflagellate Gymnodinium brevis. Four studies were done: dose response, northern analysis, immunohistochemistry and neurodegeneration. We found that neonatal rats are much more sensitive to brevetoxin than adult rats. The effectiveness of c-fos as a biomarker is being investigated, because of the high basal expression in young animals. The neurodegeneration, although not available yet, should provide valuable information.

  11. Functional characteristics of neonatal rat β cells with distinct markers

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    Martens, G A; Motté, E; Kramer, G

    2014-01-01

    twofold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal β cells at a developmental crossroad: they showed advanced endocrine differentiation when specifically analyzed for their mRNA/protein level of classical neuroendocrine markers....... On the other hand, discrete neonatal β cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, delta-like 1 homolog (DLK1) was used to investigate whether neonatal β cells with basal hyperactivity corresponded to a more immature subset with high DLK1......Neonatal β cells are considered developmentally immature and hence less glucose responsive. To study the acquisition of mature glucose responsiveness, we compared glucose-regulated redox state, insulin synthesis, and secretion of β cells purified from neonatal or 10-week-old rats...

  12. Histopathological alterations in neonate after in utero irradiation of rats

    International Nuclear Information System (INIS)

    Abdel Gawad, I.I.

    2000-01-01

    Series of experiments were performed to study the histopathological changes induced in embryonic tissue during various stages of gestation in female rats after gamma irradiation. Pregnant rats were exposed to doses 0.5, 1,2 and 3 Gy on 9 th 12 th and 15 th days of gestation. Histopathological changes were detected in tissues of neonates, namely, liver ileum, kidney, brain, spleen, suprarenal, thymus, lungs and heart. These tissues showed variable degrees of radiation induced tissue changes. For quantifying these changes arbitrary scores were formulated to assess the type and severity of changes observed tissues of thirty six neonates randomly selected after radiation exposure of pregnant animals as scheduled

  13. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups.

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    Golden, Honey B; Gollapudi, Deepika; Gerilechaogetu, Fnu; Li, Jieli; Cristales, Ricardo J; Peng, Xu; Dostal, David E

    2012-01-01

    Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FBs) serve as in vitro models for studying fundamental mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Both cell types are relatively easy to culture as monolayers and can be manipulated using molecular and pharmacological tools. Because NRVM cease to proliferate after birth, and FBs undergo phenotypic changes and senescence after a few passages in tissue culture, primary cultures of both cell types are required for experiments. Below we describe methods that provide good cell yield and viability of primary cultures of NRVM and FBs from 0 to 3-day-old neonatal rat pups.

  14. Grape seed proanthocyanidins extract promotes bone formation in rat's mandibular condyle.

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    Ishikawa, Makoto; Maki, Kenshi; Tofani, Iwan; Kimura, Kyoko; Kimura, Mitsutaka

    2005-02-01

    We studied the effect of dietary supplementation with grape seed proanthocyanidins extract (GSPE) 3 mg added in 100 g high-calcium diet with a calcium content of 1697 mg 100 g(-1) on mandibular condyle bone debility, which was induced by a low-calcium diet. Forty Wistar male rats, 5 week old, were randomly divided into control (Co), low-calcium diet (LC), low-calcium/high-calcium diet (LCH), and low-calcium/high-calcium with supplementary GSPE diet (LCHG) groups for 6 wk. Bone formation of the mandibular condyle was measured using peripheral quantitative computed tomography (pQCT). Significant differences were not seen among the four groups for body weight, measured weekly. The LCHG group scored significantly higher in cortical bone density, total bone cross-sectional area, cortical bone cross-sectional area, cortical bone mineral content, total bone density, total bone mineral content, and in the stress-strain index to the reference axis x when compared with the LCH group. We concluded that a high-calcium diet combined with GSPE supplementation is more effective in reversing mandibular condyle bone debility in rats than is a low-calcium diet, standard diet, or high-calcium diet alone.

  15. Neonatal rat hearts cannot be protected by ischemic postconditioning

    Czech Academy of Sciences Publication Activity Database

    Doul, J.; Charvátová, Z.; Ošťádalová, Ivana; Kohutiar, M.; Maxová, H.; Ošťádal, Bohuslav

    2015-01-01

    Roč. 64, č. 6 (2015), s. 789-794 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : neonatal rats * ischemic postconditioning * tolerance to ischemia * contractile function * lactate dehydrogenase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  16. Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Charvátová, Z.; Ošťádalová, Ivana; Zicha, Josef; Kuneš, Jaroslav; Maxová, H.; Ošťádal, Bohuslav

    2012-01-01

    Roč. 61, Suppl.1 (2012), S145-S153 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal spontaneously hypertensive rats * contractile function * ischemic preconditioning * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

  17. Synchronization of motor neurons during locomotion in the neonatal rat

    DEFF Research Database (Denmark)

    Tresch, Matthew C.; Kiehn, Ole

    2002-01-01

    We describe here the robust synchronization of motor neurons at a millisecond time scale during locomotor activity in the neonatal rat. Action potential activity of motor neuron pairs was recorded extracellularly using tetrodes during locomotor activity in the in vitro neonatal rat spinal cord. A...... synchronization described here might be involved in activity-dependent processes during development or in the coordination of individual motor neurons into a functional population underlying behavior.......We describe here the robust synchronization of motor neurons at a millisecond time scale during locomotor activity in the neonatal rat. Action potential activity of motor neuron pairs was recorded extracellularly using tetrodes during locomotor activity in the in vitro neonatal rat spinal cord....... Approximately 40% of motor neuron pairs recorded in the same spinal segment showed significant synchronization, with the duration of the central peak in cross-correlograms between motor neurons typically ranging between ∼ 30 and 100 msec. The percentage of synchronized motor neuron pairs was considerably higher...

  18. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  19. Imaging neonates and children with Pierre Robin sequence before and after mandibular distraction osteogenesis: what the craniofacial surgeon wants to know

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    Meyers, Arthur B. [Children' s Hospital of Wisconsin, Department of Imaging, Medical College of Wisconsin, P.O. Box 1997, Milwaukee, WI (United States); Zei, Markus G. [Medical College of Wisconsin, Milwaukee, WI (United States); St. Louis University School of Medicine, St. Louis, MO (United States); Denny, Arlen D. [Children' s Hospital of Wisconsin, Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI (United States)

    2015-08-15

    Pierre Robin sequence is characterized by micrognathia and glossoptosis causing upper airway obstruction. Mandibular distraction osteogenesis is a mandibular lengthening procedure performed in neonates and children with Pierre Robin sequence to alleviate airway compromise. This pictorial review demonstrates the role of imaging in the preoperative and postoperative assessment of these children. It is important for pediatric radiologists to know what information about the mandible and airway the craniofacial surgeon needs from preoperative imaging and to identify any complications these children may encounter after surgery. (orig.)

  20. Metabolic aspects of neonatal rat islet hypoxia tolerance.

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    Hyder, Ayman; Laue, Christiane; Schrezenmeir, Jürgen

    2010-01-01

    Sensitivity of pancreatic islets to hypoxia is one of the most important of the obstacles responsible for their failure to survive within the recipients. The aim of this study was to compare the in vitro hypoxia tolerance of neonatal and adult rat islet cells and to study the glucose metabolism in these cells after exposure to hypoxia. Islet cells from both age categories were cultured in different hypoxic levels for 24 h and insulin secretion and some metabolites of glucose metabolism were analysed. Glucose-stimulated insulin secretion decreased dramatically in both cell preparations in response to the decrease in oxygen level. The reduction of insulin secretion was more detectable in adult cells and started at 5% O(2), while a significant reduction was obtained at 1% O(2) in neonatal cells. Moreover, basal insulin release of neonatal cells showed an adaptation to hypoxia after a 4-day culture in hypoxia. Intracellular pyruvate was higher in neonatal cells than in adult ones, while no difference in lactate level was observed between them. Similar results to that of pyruvate were observed for adenosine triphosphate (ATP) and the second messenger cyclic adenosine monophosphate (cAMP). The study reveals that neonatal rat islet cells are more hypoxia-tolerant than the adult ones. The most obvious metabolic observation was that both pyruvate and lactate were actively produced in neonatal cells, while adult cells depended mainly on lactate production as an end-product of glycolysis, indicating a more enhanced metabolic flexibility of neonatal cells to utilize the available oxygen and, at the same time, maintain metabolism anaerobically.

  1. Neonatal morphine enhances nociception and decreases analgesia in young rats.

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    Zhang, Guo Hua; Sweitzer, Sarah M

    2008-03-14

    The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

  2. A magnetic resonance imaging study on changes in rat mandibular bone marrow and pulp tissue after high-dose irradiation

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    Lee, Wan; Lee, Byung Do [Dept. of Oral and Maxillofacial Radiology and Wonkwang Dental Research Institute, College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Lee, Kang Kyoo [Dept. of Radiation Oncology, School of Medicine, Wonkwang University, Iksan (Korea, Republic of); Koh, Kwang Joon [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2014-03-15

    This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow.

  3. A magnetic resonance imaging study on changes in rat mandibular bone marrow and pulp tissue after high-dose irradiation

    International Nuclear Information System (INIS)

    Lee, Wan; Lee, Byung Do; Lee, Kang Kyoo; Koh, Kwang Joon

    2014-01-01

    This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow.

  4. Abdominal expiratory muscle activity in anesthetized vagotomized neonatal rats.

    Science.gov (United States)

    Iizuka, Makito

    2009-05-01

    The pattern of respiratory activity in abdominal muscles was studied in anesthetized, spontaneously breathing, vagotomized neonatal rats at postnatal days 0-3. Anesthesia (2.0% isoflurane, 50% O(2)) depressed breathing and resulted in hypercapnia. Under this condition, abdominal muscles showed discharge late in the expiratory phase (E2 activity) in most rats. As the depth of anesthesia decreased, the amplitude of discharges in the diaphragm and abdominal muscles increased. A small additional burst frequently occurred in abdominal muscles just after the termination of diaphragmatic inspiratory activity (E1 or postinspiratory activity). Since this E1 activity is not often observed in adult rats, the abdominal respiratory pattern likely changes during postnatal development. Anoxia-induced gasping after periodic expiratory activity without inspiratory activity, and in most rats, abdominal expiratory activity disappeared before terminal apnea. These results suggest that a biphasic abdominal motor pattern (a combination of E2 and E1 activity) is a characteristic of vagotomized neonatal rats during normal respiration.

  5. Differential response of risedronate on tibial and mandibular bone quality in glucocorticoid-treated growing rats

    International Nuclear Information System (INIS)

    Fujita, Yuko

    2008-01-01

    Glucocorticoids induce bone loss and retard bone growth in children. In this study we investigated the effect of treatment with risedronate on glucocorticoid -prednisolone-induced decreases in bone density, quality, strength and growth of the tibia and mandible in growing rats. Trabecular and cortical bone structure was measured by peripheral quantitative computed tomography (pQCT) and three-dimensional (3D) micro-computed tomography (micro-CT). Indicators of bone strength were calculated from cortical bone density and the modulus of sections obtained from pQCT analysis. Tibial and mandibular bone sizes were also measured. Prednisolone decreased the bone growth of both tibia and mandible. It also caused deterioration of trabecular and cortical bone structure and strength in the mandible, and in cortical bone in the tibia, but had no effect on trabecular bone in the tibia. Risedronate inhibited the prednisolone-induced decreases in tibial width and mandibular length and height but did not improve the retardation of longitudinal bone growth. Risedronate prevented prednisolone-induced deterioration of trabecular and cortical bone architecture. In the mandible, this protective effect of risedronate was accompanied by an increase in cortical bone density and in bone strength. These findings show that risedronate inhibits prednisolone-induced loss of bone density, structure, decrease in bone strength, and retardation of bone growth in the mandible in young growing rats. (author)

  6. Ultrasound to stimulate mandibular bone defect healing : A placebo-controlled single-blind study in rats

    NARCIS (Netherlands)

    Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B

    Purpose: Because of the limitations of the body to heal large maxillofacial bone defects, an attempt was made to stimulate mandibular defect healing with low intensity pulsed ultrasound in rats. This ultrasound consists of a 1.5-MHz pressure wave administered in pulses of 200 musec, with an average

  7. The effects of the low calcium diet and irradiation on the mandibular condyle of rats

    International Nuclear Information System (INIS)

    Ahn, Hee Mun; Lee, Sang Rae

    1993-01-01

    This study was performed to investigate the changes of mandibular condyle by low diet and the effects of irradiation on the bone in ofteoporotic state. In order to carry out this experiment, 80 served-week old Sprague-Dawley strain rats about 150gm were selected and equally divided into one experimental group of 40 rats and one control group with the remainder. The experimental group and the control group of 40 rats and one control group with the remainder. The experimental group and the control group were then subdivided into two group and exposed to irradiation. The two irradiation groups received a single dose of 20 Gy on the jaw area only and irradiated with a cobalt-60 teletherapy unit. The rats in the control and experimental groups were serially terminated by fours on the 3rd, the 7th, the 14th, and the 21st day after irradiation. After termination, both sides of the dead rats mandibular condyle were removed and fixed with 10% neutral formalin. The bone mineral density of mandibular condle was measured by use of dual energy X-ray with Hitex HA-80 (Hitex Co., Japan). Thereafter, the obtained radiographs were observed, and the mandibular condyle was further decalcified and embedded in paraffin as the general method. The specimen sectioned and stained with hematoxylin-eosin, PAS and Rabbit Anti-Human Tumor Necrosis Factor-α observed by a light microscope. The obtained results were as follows: 1. In the non-irradiated group with low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days, and decrease the number of trabeculae of the condyle and resorption of the calcified cartilaginous zone were observed after 3 days. On microscopic observation, the number and size of trabecular were decreased after 7 days of experiment. 2. In the irradiated group with the low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days and resorption of the calcified cartilaginous zone and decrease the number and

  8. The use of Portland cement in the repair of mandibular fractures in rats Uso de cimento Portland no reparo de fratura mandibular em ratos

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    Reginaldo Inojosa Carneiro Campello

    2011-12-01

    Full Text Available PURPOSE: To evaluate the bone healing of mandibular fractures following the use of Portland cement. METHODS: Thirty-two male Wistar rats were divided into control and experimental groups. In the control group the rats were submitted to a mandibular fracture, which was reduced, and the soft tissues were sutured. In the experimental group the rats had the mandibular fracture reduced and maintained with the Portland cement. The animals were euthanized 7 and 21 days after surgery by injecting a lethal dose of anesthetic. The following variables were studied: weight of the animals, radiographic images, histopathological features and time of surgery. RESULTS: A weight loss was observed in the specimens of both groups at the different times of evaluation, a greater difference in weight before and after surgery being found in the experimental group, which was statistically significant (p OBJETIVO: Avaliar a reparação óssea de fratura mandibular após o uso do cimento Portland (CP. MÉTODOS: Trinta e dois ratos machos Wistar foram divididos em grupo controle e grupo experimental. No grupo controle os ratos foram submetidos à fratura, redução e manutenção dos seguimentos com sutura dos tecidos moles. No grupo experimental foram submetidos a fratura, redução e manutenção dos segmentos fraturados com CP e sutura dos tecidos. Os animais foram eutanasiados com sete e 21 dias de pós-operatório através da injeção de dose letal dos anestésicos adotados. As variáveis estudadas foram: peso dos animais, avaliação tomográfica, avaliação histológica e tempo cirúrgico. RESULTADOS: Perda de peso foi observada nos espécimes de ambos os grupos nos diferentes intervalos de tempo considerados, sendo maior a diferença de peso antes e após cirurgia para o grupo experimental, que foi estatisticamente significante (p<0,05; p=0,041. Do ponto de vista histológico para a margem de erro fixada (5,0% as duas únicas diferenças significativas (p<0

  9. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  10. Effects of young-coconut juice on increasing mandibular cancellous bone in orchidectomized rats: Preliminary novel findings

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    Pranee Suwanpal

    2011-12-01

    Full Text Available Androgens play a very important role in building the skeleton in young adults and help to prevent bone loss andosteoporosis in aging men. In addition, in hypogonadism or elderly men, bone mass has been related to estrogen levels ratherthan to testosterone. Estrogen replacement therapy has therefore been proposed to prevent bone loss in males as well as infemales. Estrogen, however, has been considered to be one of the hormonal risk factors for benign prostatic hyperplasia andprostate cancer and also has other side effects. Young coconut juice (YCJ presumably containing phytoestrogen was investigatedin the present study for its possible beneficial effects on delaying osteoporosis using a male rat model, and by this totest the possibility that it might be able to replace estrogen replacement therapy without side effects. In this study, mandibularcancellous bone was used as the osteoporotic model. Using the same model, we have previously found that total cartilagethickness particularly the hypertrophic zone of mandibular condylar cartilage was thicker in the sham-operated rats receivingYCJ orally fed for a 14 day period, compared with sham, orchidectomized animal, orchidectomized rats receiving estradiolbenzoate, and orchidectomized rats receiving YCJ. The present study confirmed our former study that mandibular cancellousbone in the sham-operated rats and in the orchidectomized rats receiving YCJ orally fed for a 14–day period were thicker thanthose of the sham and orchidectomized rat groups. This study results are novel and they indicate that YCJ may have beneficialeffects in the treatment of osteoporosis in andropause men.

  11. Dietary loading and aggrecanase-1/TIMP-3 expression in rat mandibular condylar cartilage.

    Science.gov (United States)

    Yu, Dahai; Tiilikainen, Petri; Raustia, Aune; Pirttiniemi, Pertti

    2007-01-01

    To examine the expression of aggrecanase-1 and a tissue inhibitor of metalloproteinases (TIMP-3) in the condylar cartilage of young rats and to determine their relationship during altered dietary loading at different time points after weaning. One hundred Sprague-Dawley rats were randomly assigned to 1 of 2 groups: the soft-diet group, which served as the control group (n=50), or the hard-diet group, which served as the experimental group (n=50). Ten soft- and 10 hard-diet rats were killed at 6 hours, 12 hours, 24 hours, 48 hours, and 9 days after weaning (i.e., after initiation of diet change for hard-diet rats). The right-side temporomandibular joints (TMJs) were prepared for immunohistochemical staining. The cartilage from the left-side mandibular condyles of all 10 animals in each group was combined for Western blot analysis. Immunohistochemical analysis revealed strong staining for aggrecanase-1 localized mainly in the chondrocytes of proliferative and upper hypertrophic cartilage zones at all time points in both groups. The immunohistological expression of aggrecanase-1 was significantly higher in the hard-diet group at 12 and 24 hours than in the soft-diet group. Strong staining for TIMP-3 was mainly localized in the chondrocytes of proliferative and upper hypertrophic zones at all time points in both groups. The expression of TIMP-3 in the hard-diet group was at a significantly lower level compared to the soft-diet group at 6 hours. Western blot analysis also showed time-related differences in aggrecanase-1 and TIMP-3, but there was no significant difference between the 2 groups. The temporary change in aggrecanase-1 and TIMP-3 expression reflects the complex interaction of these enzymes in the physiologic range and cartilage response to altered dietary loading.

  12. Effects of hindlimb unloading on neuromuscular development of neonatal rats

    Science.gov (United States)

    Huckstorf, B. L.; Slocum, G. R.; Bain, J. L.; Reiser, P. M.; Sedlak, F. R.; Wong-Riley, M. T.; Riley, D. A.

    2000-01-01

    We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.

  13. Proinflammatory mediators related to orthodontically induced periapical root resorption in rat mandibular molars.

    Science.gov (United States)

    Matsumoto, Yoshiro; Sringkarnboriboon, Siripen; Ono, Takashi

    2017-11-30

    The early phase of orthodontic tooth movement involves acute inflammatory response that may induce bone resorption. The aim of this study was to localize and quantify cells in the periodontium expressing proinflammatory mediators during orthodontically induced periapical root resorption of the rat mandibular molars. The levels of proinflammatory cytokines interleukin-1 (IL-1) α and β, tumor necrosis factor-α (TNF-α), inflammatory enzymes cyclooxygenase (COX) 1 and 2, and their product prostaglandin E2 (PGE2) in the root resorption site were compared to those in the corresponding area of the untreated periodontal ligament (PDL) of physiologically drifting teeth. Continuous heavy orthodontic force was applied to the mandibular first molar for 8 and 15 days while in occlusion to induce root resorption. Frozen sections including root resorption lacunae were analyzed for the activity of non-specific esterase (NSE) and tartrate-resistant acid phosphatase (TRAP) by enzyme histochemistry and for the expression of IL-1α, IL-1β, TNF-α, COX-1, COX-2, and PGE2 by immunohistochemistry. The active root resorption lacunae had significantly more TRAP-positive multinucleated odontoclasts, whereas the number of NSE-positive cells of the monocyte-macrophage lineage did not differ from that in the control PDL. Several types of periodontal cells exhibited a significant increase in the expression of IL-1α, IL-1β, TNF-α, COX-2, and PGE2 in the root resorption zone, while COX-1 was rarely detected. These data suggest that proinflammatory mediators expressed in periodontal cells may synergistically promote apical root resorption in response to continuous heavy mechanical force applied to teeth. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

  14. Anterior mandibular displacement and condylar growth. An experimental study in the rat

    International Nuclear Information System (INIS)

    Tonge, E.A.; Heath, J.K.; Meikle, M.C.

    1982-01-01

    Anterior displacement of the mandible was produced in twenty-eight 1-month-old female rats by two methods: (1) cast-gold splints cemented to the maxillary incisor teeth and (2) a removable stainless steel mesh appliance worn 6 hours each day, during which time the animals were sedated. The controls were littermates without appliances and in the mesh group were also sedated. Animals in the splint group were killed after 24 hours, 1 week, and 1 month; those in the mesh group were killed after 24 hours and after 1 week. the condyles were removed and cultured for 24 hours in medium containing 3 H-thymidine. One condyle from each animal was processed for routine histologic and autoradiographic study. The other was digested in phosphate-buffered saline containing RNA-ase and pronase, and the specific activity of 3 H-thymidine incorporation expressed as dpm/microgramDNA. Anterior mandibular displacement produced by both methods failed to result in a significant increase in the incorporation of 3 H-thymidine into explant DNA. In the 7-day mesh experiment, however, there was a significant increase in the DNA content of the condylar explants from the displacement group, suggesting an increase in the cell population. This finding should be treated with caution because of the small numbers of animals involved, but it indicates an important area for further study. Changes in the distribution of labeled cells within the proliferative zone (PZ) were also observed autoradiographically in the mesh group, but there was little to suggest that mandibular displacement was accompanied by a significant increase in cell division within the PZ. Remodeling changes affecting both the articular tissue and the subchondral bone were a characteristic feature of the 1-month bit plane group

  15. Experimental study on healing process of rat mandibular bone fracture examined by radiological procedures

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Yukio; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-06-01

    The healing process of rat mandibular fractures was stereoscopically observed daily, using plain roentgenography in the lateral-oblique and tooth axis directions and bone scintigraphy using 99m-Tc-methylene diphosphoric acid (Tc-99m-MDP). The findings were compared with microradiograms of regional polished specimens. X-ray findings included the following. Up to 3 days after bone fracture, the fracture mesiodistally showed distinct radiolucency, with sharp and irregular fracture stump. Radiopacity of the fracture site gradually increased 7 days or later, and bone trabecular formation by callus and stump bridging started to occur at 14 days. Findings similar to those in the control group were observed 49 days or later. The inside was difficult to differentiate, irrespective of the observation time. Bone scans in the mesiodistal and buccolingual planes revealed tracer uptake in the areas of mandibular and soft tissue damage one day after bone fracture. Tracer uptake began to be seen in the fracture site 3 days later, and became marked at 14 days. Then Tc-99m DMP began to be localized and returned to the findings similar to those at 49 days. Bone scanning tended to show wider areas earlier than roentgenography. Microradiographic mesiodistal examination revealed distinct radiopacy of the fracture line for 3 days after bone fracture. Seven days later, bone resorption cavity occurred in the cortical bone around the fracture stump, along with neogenesis of callus. Neogenesis and calcification began to occur gradually, and 14 days later, the fracture osteoremodeling of the internal bone trabeculae was observed. Bone trabecular formation within the bone, however, occurred later. (N.K.).

  16. Anterior mandibular displacement and condylar growth. An experimental study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Tonge, E.A.; Heath, J.K.; Meikle, M.C.

    1982-10-01

    Anterior displacement of the mandible was produced in twenty-eight 1-month-old female rats by two methods: (1) cast-gold splints cemented to the maxillary incisor teeth and (2) a removable stainless steel mesh appliance worn 6 hours each day, during which time the animals were sedated. The controls were littermates without appliances and in the mesh group were also sedated. Animals in the splint group were killed after 24 hours, 1 week, and 1 month; those in the mesh group were killed after 24 hours and after 1 week. the condyles were removed and cultured for 24 hours in medium containing /sup 3/H-thymidine. One condyle from each animal was processed for routine histologic and autoradiographic study. The other was digested in phosphate-buffered saline containing RNA-ase and pronase, and the specific activity of /sup 3/H-thymidine incorporation expressed as dpm/microgramDNA. Anterior mandibular displacement produced by both methods failed to result in a significant increase in the incorporation of /sup 3/H-thymidine into explant DNA. In the 7-day mesh experiment, however, there was a significant increase in the DNA content of the condylar explants from the displacement group, suggesting an increase in the cell population. This finding should be treated with caution because of the small numbers of animals involved, but it indicates an important area for further study. Changes in the distribution of labeled cells within the proliferative zone (PZ) were also observed autoradiographically in the mesh group, but there was little to suggest that mandibular displacement was accompanied by a significant increase in cell division within the PZ. Remodeling changes affecting both the articular tissue and the subchondral bone were a characteristic feature of the 1-month bit plane group.

  17. Distributional variations in trabecular architecture of the mandibular bone: an in vivo micro-CT analysis in rats.

    Directory of Open Access Journals (Sweden)

    Zhongshuang Liu

    Full Text Available To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX and a sham-ovariectomy group (sham. Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012, but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005. A thickness and separation map showed that trabeculae of less than 100 μm increased by 46%, whereas trabeculae of more than 200 μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200 μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028 and bone volume fraction (p = 0.001 were also significantly decreased in the OVX group compared to the sham group.Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.

  18. Congenital Malformations in Neonates after irradiation of Rats During Pregnancy

    International Nuclear Information System (INIS)

    Abdel-Gawad, I.I.; Mohammad, M.H.M.

    2000-01-01

    Radiation is considered a teratogen during the whole period of embryonic development and fetal growth. However, the time of gestation at which irradiation takes place will affect the type of congenital malformation Induced. A study was carried out to observe various forms of congenital malformations induced after irradiation of pregnant rats to 1,2 and 3 Gy on the 9 th , 12 th and 15 th days of gestation. Various types of congenital malformations were observed in the neonates of irradiated animals as compared to controls. Most of the malformations were observed in neonates of animals irradiated with 2 and 3 Gy on the 12 th and 15 th days of gestation. This confirms that developmental anomalies occur mostly during the period of organ development. Other periods of gestation are less vulnerable to, induction of malformation after irradiation. Some representative photographs of the malformations induced such as penguin shape, absence of tail, low set ears, growth retardation and others are illustrated in the text

  19. Effect of decreased loading on the metabolic activity of the mandibular condylar cartilage in the rat.

    Science.gov (United States)

    Pirttiniemi, Pertti; Kantomaa, Tuomo; Sorsa, Timo

    2004-02-01

    The aim of this study was to measure the effect of decreased temporomandibular loading on the proliferative activity and the level of matrix production of the condylar cartilage. The effect of reduced joint loading on the activity of stromelysin-1 (MMP-3), which has been associated with conditions of articular cartilage matrix breakdown, was also examined. Eighty 14-day-old female rats were assigned to two groups. Following weaning at 20 days, the experimental group was fed a soft diet and the incisors were shortened regularly to keep them out of occlusion. The controls were fed a hard diet. The activity of tritiated thymidine incorporation and the incorporation of radiolabelled sulphur were measured 2, 6, 12, 24 and 48 hours after initiation of the experiment. The radiolabelled sulphur intake was significantly lower in the condylar cartilage of the experimental group 6-24 hours after initiation of the experiment, and tritiated thymidine activity was lower after 12-24 hours, indicating lower proliferation and matrix production. The cartilage in the experimental group showed marked immunostaining against MMP-3 in all cartilage layers 9 days after initiation of the experiment. In the control group, the staining was clearly seen only in the superficial fibrous layer and in the erosion front. A marked reduction in proliferative activity and proteoglycan synthesis in mandibular condylar cartilage was found after a continuous soft diet and suppressed incisal mastication in the rat. The results show that sufficient loading is important for condylar cartilage growth, to maintain both ideal proliferation and matrix chondrocyte production.

  20. Development of Chemosensitivity in Neurons from the Nucleus Tractus Solitarii (NTS) of Neonatal Rats

    Science.gov (United States)

    Conrad, Susan C.; Nichols, Nicole L.; Ritucci, Nick A.; Dean, Jay B.; Putnam, Robert W.

    2009-01-01

    We studied the development of chemosensitivity during the neonatal period in rat Nucleus tractus solitarii (NTS) neurons. We determined the percentage of neurons activated by hypercapnia (15% CO2) and assessed the magnitude of the response by calculating the chemosensitivity index (CI). There were no differences in the percentage of neurons that were inhibited (9%) or activated (44.8%) by hypercapnia or in the magnitude of the activated response (CI 164±4.9%) in NTS neurons from neonatal rats of all ages. To assess the degree of intrinsic chemosensitivity in these neurons we used chemical synaptic block medium and the gap junction blocker carbenoxolone. Chemical synaptic block medium slightly decreased basal firing rate but did not affect the percentage of NTS neurons that responded to hypercapnia at any neonatal age. However, in neonates aged neonates, chemical synaptic block medium increased CI. Carbenoxolone did not significantly alter the number of NTS neurons activated by hypercapnia in neonatal rats of any age. In summary, the response of NTS neurons from neonatal rats appears to be intrinsic and largely unchanged throughout early development. In young neonates (

  1. An experimental study of mandibular fracture wound healing in the calcium deficient rat

    International Nuclear Information System (INIS)

    Lee, Sang Hoon; Wang, Eui Hwan; Lee, Sang Rae

    1997-01-01

    The purpose of this study was to investigate effects of osteoporosis on fracture wound healing in the calcium deficient rat. To research the experiment some ten-week old Wistar strain rats with approximately 300 gms weight were selected. Then, the rats were divided into two groups : Normal diet group (rats given a normal diet before and after bone fracture) and Low calcium diet group (rats given a low calcium diet before and after bone fracture). Both groups had been provided with each diet for three weeks. When the rats became thirteen weeks old, the mandibular angle of rats in both groups was artificially fractured for test. The healing of fracture wounds was reviewed by using soft x-ray radiography and 99m Tc-MDP bone scan and also histopathologic examination. The obtained results were as follows : 1. The radiolucency of the fracture site for the Normal diet group started to decrease from the 14th day since the experiment was made, while the Low calcium diet group began decrease in the radiolucency from the 21st day of the experiment . The radiolucency for the normal diet group disappeared at the 42nd day, but one for the Low calcium diet group disappeared at the 56th day of the experiment. 2. The highest uptake rate of 99m Tc-MDP stood at the 14th day of the experiment in the Normal diet group and the Low calcium diet group's maximum rate was recorded at the 21st day of the experiment. These both groups were gradually experiencing decrease in the uptake rate as the experiment time was going on. However, the uptake rate in the Low calcium diet group was lower than one in the Normal diet group. 3. For the Normal diet group, the newly formed trabecular, which were similar to one of the surrounding bone, were seen at the 42nd day of the experiment. On the other hand, the Low claium diet group showed at the 56th day of the experiment that the osteoporotic findings looked weak, irregular trabecular, and also large bone marrow space were observed clearly. As a result

  2. Stress/aggressiveness-induced immune changes are altered in adult rats submitted to neonatal malnutrition.

    Science.gov (United States)

    Barreto-Medeiros, Jairza; Queiros-Santos, Adenilda; Cabral-Filho, José Eulálio; Ferreira E Silva, Wylla Tatiana; Leandro, Carol Góis; Deiró, Tereza Cristina; Manhaes-de-Castro, Raul; Machado Barbosa de-Castro, Célia Maria

    2007-01-01

    Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. Male Wistar rats were distributed to one of two groups according to their mothers' diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.

  3. Cardiac and plasma lipid profiles in response to acute hypoxia in neonatal and young adult rats

    Directory of Open Access Journals (Sweden)

    Raff Hershel

    2010-01-01

    Full Text Available Abstract Background The physiological and biochemical responses to acute hypoxia have not been fully characterized in neonates. Fatty acids and lipids play an important role in most aspects of cardiac function. Methods We performed comprehensive lipid profiling analysis to survey the changes that occur in heart tissue and plasma of neonatal and young adult rats exposed to hypoxia for 2 h, and following 2 h of recovery from hypoxia. Results Cardiac and plasma concentrations of short-chain acylcarnitines, and most plasma long-chain fatty acids, were decreased in hypoxic neonates. Following recovery from hypoxia, concentrations of propionylcarnitine, palmitoylcarnitine, stearoylcarnitine were increased in neonatal hearts, while oleylcarnitine and linoleylcarnitine concentrations were increased in neonatal plasma. The concentrations of long-chain fatty acids and long-chain acylcarnitines were increased in the hearts and plasma of hypoxic young adult rats; these metabolites returned to baseline values following recovery from hypoxia. Conclusion There are differential effects of acute hypoxia on cardiac and plasma lipid profiles with maturation from the neonate to the young adult rat. Changes to neonatal cardiac and plasma lipid profiles during hypoxia likely allowed for greater metabolic and physiologic flexibility and increased chances for survival. Persistent alterations in the neonatal cardiac lipid profile following recovery from hypoxia may play a role in the development of rhythm disturbances.

  4. The effect of iron and/or lactose on strontium metabolism in neonatal and weanling rats

    International Nuclear Information System (INIS)

    Gruden, N.; Mataushicj, S.

    1988-01-01

    Iron-fortified cow's milk increased strontium-85 retention in the femur and brain of neonatal rats by 16-44%, irrespective of the presence or absence of lactose. A similar effect was observed in the brain of weaning rats if milk was enriched with lactose and was not altered by simultaneous addition of iron. (author). 18 refs.; 1 tab

  5. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian

    2013-01-01

    fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial...... cells (p = 0.024) in the mPFC of neonatal phencyclidine rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following...

  6. Effect of Maternal Diabetes on Cerebellum Histomorphometry in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Z Khaksar

    2010-04-01

    Full Text Available Introduction: In pregnant mothers, maternal diabetes occurs when pancreas can't produce enough insulin resulting in increased blood glucose levels in the mother and subsequently in the fetus. This investigation was conducted to evaluate the effects of maternal diabetes on cerebellum of offspring of diabetic mothers (ODM, which was carried out at the veterinary faculty of Shiraz University in 2007-2008. Methods: This was an experimental study that included sixteen normal adult female rats divided in two groups. Diabetes was induced in one group by Alloxan agent. Both groups became pregnant by natural mating . At 7, 14, 21 and 28 days after birth, the cerebellum of all offsprings were collected and the weight of neonates was also measured. After producing histological slides, Olympus BX51 microscope and ‍‍‍‍‍‍‍ Olysia softwarwere used. Various histological parameters used included gray and white matters thicknesses (µ, the number of cells in gray and white matter separately per unit and the ratio of gray matter to white matter. Results: Cerebellar parameters decreased in ODM as compared to the control group. The body weight of ODM was significantly more than that of the control group (p< 0.05. Conclusions: Maternal hyperglycaemia exhibited deleterious effects on cerebellum during fetal life, which remained persistent during postneonatal period. Maternal diabetes also resulted in reduction of number of cells and thicknesses of both gray and white matter.

  7. Mechanisms by which neonatal testosterone exposure mediates sex differences in impulsivity in prepubertal rats.

    Science.gov (United States)

    Bayless, Daniel W; Darling, Jeffrey S; Daniel, Jill M

    2013-11-01

    Neonatal testosterone, either acting directly or through its conversion to estradiol, can exert organizational effects on the brain and behavior. The goal of the current study was to examine sex differences and determine the role of neonatal testosterone on prefrontal cortex-dependent impulsive choice behavior in prepubertal rats. Male and female prepubertal rats were tested on the delay-based impulsive choice task. Impulsive choice was defined as choosing an immediate small food reward over a delayed large reward. In a first experiment to examine sex differences, males made significantly more impulsive choices than did females. In a second experiment to examine the organizational effects of testosterone, females treated with neonatal testosterone made significantly more impulsive choices than did control females and their performance was indistinguishable from that of control males. In a third experiment to determine if the effect of testosterone on performance is due to the actions of androgens or estrogens through its conversion to estradiol, males treated neonatally with the aromatase inhibitor formestane, which blocks the conversion of testosterone to estradiol, females treated neonatally with the non-aromatizable androgen dihydrotestosterone, and females treated neonatally with estradiol made significantly more impulsive choices than did control females and their performance was indistinguishable from that of control males. Results indicate that male pubertal rats display increased impulsive choice behavior as compared to females, that this sex difference results from organizing actions of testosterone during the neonatal period, and that this effect can result from both androgenic and estrogenic actions. © 2013.

  8. THE EFFECT OF OESTROGEN AND OR CALCIUM VITAMIN D3 ON THE MANDIBULAR HEIGHT OF POST OVARIECTOMIZED WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Henri D. Henri

    2015-07-01

    Full Text Available One of the major health problems in elderly women is osteoporosis post menopause. Dentists must be aware of the disease since its involvement on the jaw. Nowadays, there are a lot of researches on correlation of osteopororsis and mandible but only few concentrate on hormonal substitution therapy and/or Calcium-vitamin D3 (Ca-Vit D3. This research is to evaluate the effect of hormonal substitiution therapy and/or Ca-vit D3 on mandibular height. Forty five rats used in this research and divided into nine groups: one control group, two ovariectomized (OVX groups, two OVX groups treated with estrogen, two OVC groups treated with Ca-vit D3, two OVC groups treated with estrogen and Ca-vit D3. All of the rats except the control group were ovariectomized as model for postmenopausal estrogen deficiency state. The treatment was done in two or four weeks. The animals were killed with cervical dislocation, the mandible were excised and soaked on Hydrogen Peroxide 10%. Then the mandible's heights on right buccal side were measured from the manduble base to the alveolar crest. It is concluded that hormonal substitution therapy and combination of the hormonal substitution therapy and Ca-vit D3 can maintain the normal mandibular height. Mandibular height of groups with therapy using Ca-vit D3 have slightly lower means compared to control group but without significant difference statistically. The best therapy is combination of hormonal substitution therapy and Ca-vit D3.

  9. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Directory of Open Access Journals (Sweden)

    Gabriella Lopes DE REZENDE BARBOSA

    2016-01-01

    Full Text Available Abstract The purpose of this study was to perform a microcomputed tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a microcomputed tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey’s post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05. The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues.

  10. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Rezende Barbosa, Gabriella Lopes de; Almeida, Solange Maria de, E-mail: gabriellalopes@live.com [Universidade de Campinas (UNICAMP), Piracicaba, SP (Brazil). Escola de Odontologia. Departmento de Diagnostico Oral; Pimenta, Luiz Andre [University of North Carolina at Chapel Hill, School of Dentistry, Department of Dental Ecology, Chapel Hill, NC (United States)

    2016-05-01

    The purpose of this study was to perform a micro computerized tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a micro computerized tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey's post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05). The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues. (author)

  11. Influence of iron on plutonium absorption by the adult and neonatal rat

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Ruemmler, P.S.; Buschbom, R.L.

    1986-01-01

    To determine how iron affects plutonium absorption, adult rats were gavaged with 238 Pu nitrate (pH 2) after they had been fed an iron-deficient diet or treated with iron supplements. Neonatal rats born to dams on an iron-deficient diet were also gavaged with 238 Pu. An iron-deficient diet resulted in enhanced 238 Pu absorption both in the adults and in neonates born to iron-deficient dams. Ferric iron increased 238 Pu absorption 12-fold in adult rats; injected iron-dextran reduced that increase; gavaged ferrous iron reduced 238 Pu absorption to one-third of the control value. Rat neonates absorbed 30 to 40 times as much 238 Pu as adults; absorption was lowered in groups that received iron supplements: Iron-dextran caused a 50% reduction; ferric iron, 95%; and ferrous iron, greater than 95%. The results demonstrate an effect of the oxidation state of iron on plutonium absorption in adult rats different from that observed in suckling rats. The results suggest that the high rate of 238 Pu absorption by neonatal animals is due not only to the permeability of their intestines but also to their high demand for iron

  12. Neonatal glucocorticosteroid treatment causes systolic dysfunction and compensatory dilatation in early life : Studies in 4-week-old prepubertal rats

    NARCIS (Netherlands)

    Bal, Miriam P; de Vries, Willem B; van der Leij, Feike R; van Oosterhout, Matthijs F M; Berger, Rudolphus; Baan, Jan; van der Wall, Ernst E; van Bel, Frank; Steendijk, Paul

    Glucocorticosteroid treatment is widely used to prevent chronic lung disease in premature infants, Recent studies in adult rats, treated with dexamethasone in the neonatal period, report negative long-term effects on the heart and severely reduced life expectancy. We treated neonatal rats with

  13. Ethanol-induced swelling in neonatal rat primary astrocyte cultures.

    Science.gov (United States)

    Aschner, M; Allen, J W; Mutkus, L A; Cao, C

    2001-05-11

    We tested the hypothesis that astrocytes swell in response to ethanol (EtOH) exposure. The experimental approach consisted of an electrical impedance method designed to measure cell volume. In chronic experiments, EtOH (100 mM) was added to the culture media for 1, 3, or 7 days. The cells were subsequently exposed for 15 min to isotonic buffer (122 mM NaCl) also containing 100 mM EtOH. Subsequently, the cells were washed and exposed to hypotonic buffer (112 mM NaCl) containing 100 mM mannitol. Chronic exposure to EtOH led to a marked increase in cell volume compared with control cells. Specific anion cotransport blockers, such as SITS, DIDS, furosemide, or bumetanide, when simultaneously added with EtOH to hyponatremic buffer, failed to reverse the EtOH-induced effect on swelling. In acute experiments, confluent neonatal rat primary astrocyte cultures were exposed to isotonic media (122 mM NaCl) for 15 min, followed by 45-min exposure to hypotonic media (112 mM NaCl, mimicking in vivo hyponatremic conditions associated with EtOH withdrawal) in the presence of 0-100 mM EtOH. This exposure led to a concentration-dependent increase in cell volume. Combined, these studies suggest that astrocytes exposed to EtOH accumulate compensatory organic solutes to maintain cell volume, and that in response to hyponatremia and EtOH withdrawal their volume increases to a greater extent than in cells exposed to hyponatremia alone. Furthermore, the changes associated with EtOH are osmotic in nature, and they are not reversed by anion cotransport blockers.

  14. Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival

    Science.gov (United States)

    Kennedy, Rebekah C. M.; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A.; Hu, Pan; Bae, Jiyoung; Gee, Nancy A.; Lasley, Bill L.; Zhao, Ling

    2015-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure. PMID:24803507

  15. Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China); Wang, Zhenming; Lu, Xiong [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan (China); Yimin [Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo (Japan); Oda, Kimimitsu [Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Amizuka, Norio [Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo (Japan); Li, Minqi, E-mail: liminqi@sdu.edu.cn [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China)

    2015-04-01

    The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8 weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. - Highlights: • More information on collagen material was added in the revised manuscript. • Masson–Goldner trichrome stain was performed for histomorphometry. • More specific information on calcitriol was supplemented in the Discussion section. • The MOD of ALP and Runx2 was explained in more detail. • The inhibition of osteoclastogenesis was described more accurately in the second paragraph of the discussion.

  16. Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

    Science.gov (United States)

    Swann, Hillary E; Kauer, Sierra D; Allmond, Jacob T; Brumley, Michele R

    2017-02-01

    Quipazine is a 5-HT 2A -receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Long-term behavioral effects of repetitive pain in neonatal rat pups.

    Science.gov (United States)

    Anand, K J; Coskun, V; Thrivikraman, K V; Nemeroff, C B; Plotsky, P M

    1999-06-01

    Human preterm neonates are subjected to repetitive pain during neonatal intensive care. We hypothesized that exposure to repetitive neonatal pain may cause permanent or long-term changes because of the developmental plasticity of the immature brain. Neonatal rat pups were stimulated one, two, or four times each day from P0 to P7 with either needle prick (noxious groups N1, N2, N4) or cotton tip rub (tactile groups T1, T2, T4). In groups N2, N4, T2, T4 stimuli were applied to separate paws at hourly intervals;each paw was stimulated only once a day. Identical rearing occurred from P7 to P22 days. Pain thresholds were measured on P16, P22, and P65 (hot-plate test), and testing for defensive withdrawal, alcohol preference, air-puff startle, and social discrimination tests occurred during adulthood. Adult rats were exposed to a hot plate at 62 degrees C for 20 s, then sacrificed and perfused at 0 and 30 min after exposure. Fos expression in the somatosensory cortex was measured by immunocytochemistry. Weight gain in the N2 group was greater than the T2 group on P16 (p memory in the social discrimination test (p somatosensory cortex in the T4 group compared with the N4 group (p < 0.05), whereas no differences occurred just after exposure. These data suggest that repetitive pain in neonatal rat pups may lead to an altered development of the pain system associated with decreased pain thresholds during development. Increased plasticity of the neonatal brain may allow these and other changes in brain development to increase their vulnerability to stress disorders and anxiety-mediated adult behavior. Similar behavioral changes have been observed during the later childhood of expreterm neonates who were exposed to prolonged periods of neonatal intensive care.

  18. Hyperleptinemia in Neonatally Overfed Female Rats Does Not Dysregulate Feeding Circuitry

    Directory of Open Access Journals (Sweden)

    Ilvana Ziko

    2017-10-01

    Full Text Available Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY, agouti-related peptide (AgRP, and pro-opiomelanocortin (POMC neurons within the regions of the hypothalamus responsible for control of energy balance and food intake. Female rats that are overfed during the first weeks of their life experience similar changes in circulating leptin levels as well as in their body weight. However, it has not yet been studied whether these metabolic changes are associated with the same central effects as observed in males. Here, we hypothesized that hyperleptinemia associated with neonatal overfeeding would lead to changes in central feeding circuitry in females as it does in males. We assessed hypothalamic NPY, AgRP, and POMC gene expression and immunoreactivity at 7, 12, or 14 days of age, as well as neuronal activation in response to exogenous leptin in neonatally overfed and control female rats. Neonatally overfed female rats were hyperleptinemic and were heavier than controls. However, these metabolic changes were not mirrored centrally by changes in hypothalamic NPY, AGRP, and POMC fiber density. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the female and male central systems to respond to changes in the early life nutritional environment.

  19. Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

    NARCIS (Netherlands)

    van de Wall, E. H. E. M.; Wielinga, P. Y.; Strubbe, J. H.; van Dijk, G.

    2006-01-01

    Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose

  20. Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

    Science.gov (United States)

    Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

    2014-06-01

    Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

  1. Gastrointestinal absorption and retention of plutonium-238 in neonatal rats and swine

    International Nuclear Information System (INIS)

    Sullivan, M.F.

    1978-01-01

    Neonatal rats gavaged with 237 Pu or 238 Pu retained a substantial quantity in gut mucosa for a week but absorbed only 2.9% of the 237 Pu. After 140 days the amount retained fell to half that initially deposited. Newborn swine also retained large amounts in the gut and absorbed about 40% of the dose

  2. The Effect of Alpha Tocopherol on Body Organs of Neonatal Rats ...

    African Journals Online (AJOL)

    The objective of this work was to investigate the effects of -Tocopherol (vitamin E) on the organs of neonatal rats exposed to Vanadium. Organ histology show that vanadium through lactation induced pathological changes including congestion and haemorrhages at the renal cortex, severe diffuse vacuolar degeneration of ...

  3. Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

    Directory of Open Access Journals (Sweden)

    Marco Sifringer

    2015-01-01

    Full Text Available Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.

  4. Does Neonatal Brain Ischemia Induce Schizophrenia-Like Behavior in Young Adult Rats?

    Czech Academy of Sciences Publication Activity Database

    Tejkalová, H.; Kaiser, M.; Klaschka, Jan; Šťastný, František

    2007-01-01

    Roč. 56, č. 6 (2007), s. 815-823 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NR8797 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : neonatal ischemia * schizophrenia * rat * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology Impact factor: 1.505, year: 2007

  5. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

    Science.gov (United States)

    Arendash, Gary W.; Gorski, Roger A.

    1982-09-01

    Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

  6. Distribution Dynamics of Recombinant Lactobacillus in the Gastrointestinal Tract of Neonatal Rats

    Science.gov (United States)

    Bao, Sujin; Zhu, Libin; Zhuang, Qiang; Wang, Lucia; Xu, Pin-Xian; Itoh, Keiji; Holzman, Ian R.; Lin, Jing

    2013-01-01

    One approach to deliver therapeutic agents, especially proteins, to the gastro-intestinal (GI) tract is to use commensal bacteria as a carrier. Genus Lactobacillus is an attractive candidate for use in this approach. However, a system for expressing exogenous proteins at a high level has been lacking in Lactobacillus. Moreover, it will be necessary to introduce the recombinant Lactobacillus into the GI tract, ideally by oral administration. Whether orally administered Lactobacillus can reach and reside in the GI tract has not been explored in neonates. In this study, we have examined these issues in neonatal rats. To achieve a high level of protein expression in Lactobacillus, we tested the impact of three promoters and two backbones on protein expression levels using mRFP1, a red fluorescent protein, as a reporter. We found that a combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei with a backbone from pLEM415 yielded the highest level of reporter expression. When this construct was used to transform Lactobacillus casei, Lactobacillus delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in all these species and colonies of transformed Lactobacillus appeared pink under visible light. To test whether orally administered Lactobacillus can be retained in the GI tract of neonates, we fed the recombinant Lactobacillus casei to neonatal rats. We found that about 3% of the bacteria were retained in the GI tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus in the stomach and small intestine than in the cecum and colon. No mortality was observed throughout this study with Lactobacillus. In contrast, all neonatal rats died within 24 hours after fed with transformed E. coli. Taken together, our results indicate that Lactobacillus has the potential to be used as a vehicle for the delivery of therapeutic agents to neonates. PMID:23544119

  7. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-01-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 μg/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 μg/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  8. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Effects of sciatic-conditioned medium on neonatal rat retinal cells in vitro

    Directory of Open Access Journals (Sweden)

    Torres P.M.M.

    1998-01-01

    Full Text Available Schwann cells produce and release trophic factors that induce the regeneration and survival of neurons following lesions in the peripheral nerves. In the present study we examined the in vitro ability of developing rat retinal cells to respond to factors released from fragments of sciatic nerve. Treatment of neonatal rat retinal cells with sciatic-conditioned medium (SCM for 48 h induced an increase of 92.5 ± 8.8% (N = 7 for each group in the amount of total protein. SCM increased cell adhesion, neuronal survival and glial cell proliferation as evaluated by morphological criteria. This effect was completely blocked by 2.5 µM chelerythrine chloride, an inhibitor of protein kinase C (PKC. These data indicate that PKC activation is involved in the effect of SCM on retinal cells and demonstrate that fragments of sciatic nerve release trophic factors having a remarkable effect on neonatal rat retinal cells in culture.

  10. Systemic evaluation of hypoxic-ischemic brain injury in neonatal rats.

    Science.gov (United States)

    Zhu, Ai-Hua; Hu, Yan-Rong; Liu, Wei; Gao, Feng; Li, Jian-Xin; Zhao, Li-Hui; Chen, Gang

    2014-06-01

    The objective of the study was to evaluate the systematically rat model of neonatal hypoxic-ischemic brain damage. The right carotid arteries of 7-day-old healthy Wistar rats were ligated, and then, the rats were subjected to an environment with 8 % of oxygen. Four weeks after the birth, neurobehavioral test, water maze test, and motor-evoked potential and neuropathologic examinations were performed. The footprint analysis showed significantly larger and instable paces in the hypoxic-ischemic group (P balance beam in the hypoxic-ischemic group was longer than the control group (P water maze test showed that the escape latency of hypoxic-ischemic group was significantly longer than that of control group (P neonatal hypoxic-ischemic brain damage and can be used for experimental research related to management of cerebral palsy.

  11. Ischemic preconditioning in chronically hypoxic neonatal rat heart

    Czech Academy of Sciences Publication Activity Database

    Ošťádalová, Ivana; Ošťádal, Bohuslav; Jarkovská, D.; Kolář, František

    2002-01-01

    Roč. 52, č. 4 (2002), s. 561-567 ISSN 0031-3998 R&D Projects: GA ČR GA305/00/1659; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : neonatal heart * chronix hypoxia * ischemic preconditioning Subject RIV: ED - Physiology Impact factor: 3.382, year: 2002

  12. Behavioral deficits in adult rats treated neonatally with glutamate

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Gandalovičová, D.; Krejčí, I.

    2005-01-01

    Roč. 27, č. 3 (2005), s. 465-473 ISSN 0892-0362 R&D Projects: GA MZd(CZ) NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : neonatal treatment * monosodium glutamate * long-term effect Subject RIV: ED - Physiology Impact factor: 1.940, year: 2005

  13. Testosterone potentiates the hypoxic ventilatory response of adult male rats subjected to neonatal stress.

    Science.gov (United States)

    Fournier, Sébastien; Gulemetova, Roumiana; Joseph, Vincent; Kinkead, Richard

    2014-05-01

    Neonatal stress disrupts development of homeostatic systems. During adulthood, male rats subjected to neonatal maternal separation (NMS) are hypertensive and show a larger hypoxic ventilatory response (HVR), with greater respiratory instability during sleep. Neonatal stress also affects sex hormone secretion; hypoxia increases circulating testosterone of NMS (but not control) male rats. Given that these effects of NMS are not observed in females, we tested the hypothesis that testosterone elevation is necessary for the stress-related increase of the HVR in adult male rats. Pups subjected to NMS were placed in an incubator for 3 h per day from postnatal day 3 to 12. Control pups remained undisturbed. Rats were reared until adulthood, and the HVR was measured by plethysmography (fractional inspired O2 = 0.12, for 20 min). We used gonadectomy to evaluate the effects of reducing testosterone on the HVR. Gonadectomy had no effect on the HVR of control animals but reduced that of NMS animals below control levels. Immunohistochemistry was used to quantify androgen receptors in brainstem areas involved in the HVR. Androgen receptor expression was generally greater in NMS rats than in control rats; the most significant increase was noted in the caudal region of the nucleus tractus solitarii. We conclude that the abnormal regulation of testosterone is important in stress-related augmentation of the HVR. The greater number of androgen receptors within the brainstem may explain why NMS rats are more sensitive to testosterone withdrawal. Based on the similarities of the cardiorespiratory phenotype of NMS rats and patients suffering from sleep-disordered breathing, these results provide new insight into its pathophysiology, especially sex-based differences in its prevalence. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  14. Osteoprotegerin gene-modified BMSCs with hydroxyapatite scaffold for treating critical-sized mandibular defects in ovariectomized osteoporotic rats.

    Science.gov (United States)

    Liu, Xian; Bao, Chongyun; Xu, Hockin H K; Pan, Jian; Hu, Jing; Wang, Ping; Luo, En

    2016-09-15

    Women with postmenopausal osteoporosis are at a high risk for fracture as their bone resorption rate exceeds bone formation rate, resulting in decreased bone mineral density and microarchitectural deterioration. Osteoprotegerin (OPG), a known therapeutic agent capable of inhibiting osteoclastogenesis, has been used in treatment of chronic bone resorptive diseases. On the other hand, bone mesenchymal stem cells (BMSCs) play an important role in bone formation. To inhibit excessive bone resorption and increase bone formation, we developed a novel therapeutic strategy by genetically modifying BMSCs for OPG delivery. The OPG gene-modified BMSCs were seeded on hydroxyapatite (HA) scaffolds to promote bone regeneration in critical-sized mandibular bone defects in ovariectomy (OVX) induced osteoporotic rats. Rat BMSCs were infected with human OPG adenoviruses (OPG-BMSCs). The gene-modified cells expressed higher OPG gene level than the control Ad-BMSCs (pOsteoprotegerin (OPG), a known therapeutic agent capable of inhibiting osteoclast cells, has been used in treatment of chronic bone resorptive diseases. To inhibit excessive bone resorption and increase bone formation, we developed a novel therapeutic strategy by genetically modifying bone marrow stem cells (BMSCs) for OPG delivery and seeding the cells on a hydroxyapatite (HA) scaffold for in vivo bone defect repair. The novel OPG-BMSC-HA constructs were able to orchestrate bone-forming BMSCs and bone-resorbing osteoclasts, demonstrating good potential for osteoporosis-related bone defect reconstruction treatments. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Transfer of milk prolactin ro the plasma of neonatal rats by intestinal absorption

    International Nuclear Information System (INIS)

    Whitworth, N.S.; Grosvenor, C.E.

    1978-01-01

    Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. 131 - labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with 131 I-labelled rat prolactin and after the pups had received 131 I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the 131 I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10.5 or 21.0 μg B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46.2 μg B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13-to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn is permeable to prolactin and that milk may constitute an exogeneous source of prolactin for the suckled offspring. (author)

  16. Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

    Science.gov (United States)

    Li, Y Q; Wong, C S

    2000-09-01

    This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

  17. Marginal zinc deficiency in pregnant rats impairs bone matrix formation and bone mineralization in their neonates.

    Science.gov (United States)

    Nagata, Masashi; Kayanoma, Megumu; Takahashi, Takeshi; Kaneko, Tetsuo; Hara, Hiroshi

    2011-08-01

    Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups and fed AIN-93G-based experimental diets containing 35 mg Zn/kg (Zn adequately supplied, N) or 7 mg Zn/kg (low level of Zn, L) from 14-day preconception to 20 days of gestation, that is, 1 day before normal delivery. Neonates were delivered by cesarean section. Litter size and neonate weight were not different between the two groups. However, in the L-diet-fed dam group, bone matrix formation in isolated neonatal calvaria culture was clearly impaired and was not recovered by the addition of Zn into the culture media. Additionally, serum concentration of osteocalcin, as a bone formation parameter, was lower in neonates from the L-diet-fed dam group. Impaired bone mineralization was observed with a significantly lower content of phosphorus in neonate femurs from L-diet-fed dams compared with those from N-diet-fed dams. Moreover, Zn content in the femur and calvaria of neonates from the L-diet group was lower than that of the N-diet-fed group. In the marginally Zn-deficient dams, femoral Zn content, serum concentrations of Zn, and osteocalcin were reduced when compared with control dams. We conclude that maternal Zn deficiency causes impairment of bone matrix formation and bone mineralization in neonates, implying the importance of Zn intake during pregnancy for proper bone development of offspring.

  18. Neonatal bladder inflammation induces long-term visceral pain and altered responses of spinal neurons in adult rats.

    Science.gov (United States)

    Kannampalli, Pradeep; Babygirija, Reji; Zhang, Jiang; Poe, Michael M; Li, Guanguan; Cook, James M; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N

    2017-03-27

    Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats. The present study investigates whether these molecular changes affect the integrative function and responses of bladder-sensitive primary afferent and spinal neurons. Neonatal bladder inflammation was induced by intravesicular injection of zymosan during postnatal (P) days 14-16. In adulthood (P60), the viscero-motor response (VMR) to visceral stimuli was significantly inhibited by intrathecal (i.t) HZ166 (GABA Aα-2 agonist) only in neonatally saline-treated, but not in neonatally zymosan-treated rats. HZ166 significantly inhibited the responses of bladder-responsive lumbosacral (LS) spinal neurons to urinary bladder distension (UBD) and slow infusion (SI) in neonatally saline-treated rats. Similar results were also observed in naïve adult rats where HZ166 produced significant inhibition of bladder-responsive spinal neurons. However, HZ166 did not inhibit responses of UBD-responsive spinal neurons from neonatally zymosan-treated rats. The drug did not attenuate the responses of UBD-sensitive pelvic nerve afferent (PNA) fibers to UBD and SI in either group of rats tested. Immunohistochemical studies showed a significantly lower level of GABA Aα-2 receptor expression in the LS spinal cord of neonatally zymosan-treated rats compared to saline-treated rats. These findings indicate that neonatal bladder inflammation leads to functional and molecular alteration of spinal GABA Aα-2 receptor subtypes, which may result in chronic visceral hyperalgesia in adulthood. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

    Science.gov (United States)

    Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

  20. Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

    Science.gov (United States)

    Alvarez, Pedro; Green, Paul G; Levine, Jon D

    2018-02-09

    Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats

    Directory of Open Access Journals (Sweden)

    Dubner Ronald

    2005-09-01

    Full Text Available Abstract Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors to compare gene expression profiles in the lumbar spinal dorsal horn (LDH of adult (P60 male rats that received neonatal CAR treatment within (at postnatal day 3; P3 and outside (at postnatal 12; P12 of the sensitive period. The data were obtained both without inflammation (at baseline and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems in the LDH ipsilateral to the

  2. Growth inhibition in rats fed inadequate and incomplete proteins: repercussion on mandibular biomechanics

    OpenAIRE

    Bozzini, Clarisa; Champin, Graciela Monica; Bozzini, Carlos Eduardo Jose; Alippi, Rosa Maria

    2015-01-01

    This study describes the effects of feeding growing rats with a diet containing inadequate and incomplete proteins on both the morphological and the biomechanical properties of the mandible. Female rats aged 30 d were fed freely with one of two diets, control (CD, 301 Cal/100g) and experimental (ED, 359 Cal/100g). CD was a standard laboratory diet, while ED was a synthetic diet containing cornflower supplemented with vitamins and minerals. Both diets had the same physical characteristics. Con...

  3. KCNQ channels are involved in the regulatory volume decrease response in primary neonatal rat cardiomyocytes

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Nielsen, Morten Schak; Grunnet, Morten

    2007-01-01

    Cardiomyocytes may experience significant cell swelling during ischemia and reperfusion. Such changes in cardiomyocyte volume have been shown to affect the electrical properties of the heart, possibly leading to cardiac arrhythmia. In the present study the regulatory volume decrease (RVD) response...... of neonatal rat cardiomyocytes was studied in intact single cells attached to coverslips, i.e. with an intact cytoskeleton. The potential contribution of KCNQ (Kv7) channels to the RVD response and the possible involvement of the F-actin cytoskeleton were investigated. The rate of RVD was significantly...... inhibited in the presence of the KCNQ channel blocker XE-991 (10 and 100 microM). Electrophysiological experiments confirmed the presence of an XE-991 sensitive current and Western blotting analysis revealed that KCNQ1 channel protein was present in the neonatal rat cardiomyocytes. Hypoosmotic cell swelling...

  4. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    Science.gov (United States)

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Neonatal monosodium glutamate treatment modifies glutamic acid decarboxylase activity during rat brain postnatal development.

    Science.gov (United States)

    Ureña-Guerrero, Mónica Elisa; López-Pérez, Silvia Josefina; Beas-Zárate, Carlos

    2003-03-01

    Monosodium glutamate (MSG) produces neurodegeneration in several brain regions when it is administered to neonatal rats. From an early embryonic age to adulthood, GABA neurons appear to have functional glutamatergic receptors, which could convert them in an important target for excitotoxic neurodegeneration. Changes in the activity of the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), have been shown after different neuronal insults. Therefore, this work evaluates the effect of neonatal MSG treatment on GAD activity and kinetics in the cerebral cortex, striatum, hippocampus and cerebellum of the rat brain during postnatal development. Neonatal MSG treatment decreased GAD activity in the cerebral cortex at 21 and 60 postnatal days (PD), mainly due to a reduction in the enzyme affinity (K(m)). In striatum, the GAD activity and the enzyme maximum velocity (V(max)) were increased at PD 60 after neonatal MSG treatment. Finally, in the hippocampus and cerebellum, the GAD activity and V(max) were increased, but the K(m) was found to be lower in the experimental group. The results could be related to compensatory mechanisms from the surviving GABAergic neurons, and suggest a putative adjustment in the GAD isoform expression throughout the development of the postnatal brain, since this enzyme is regulated by the synaptic activity under physiological and/or pathophysiological conditions.

  6. Low body weight and cardiac tolerance to ischemia in neonatal rats

    Czech Academy of Sciences Publication Activity Database

    Chvojková, Zuzana; Ošťádalová, Ivana; Ošťádal, Bohuslav

    2005-01-01

    Roč. 54, č. 4 (2005), s. 357-362 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/00/1659; GA MŠk(CZ) LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : low body weight * cardiac tolerance to ischemia * neonatal rats Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  7. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats.

    Science.gov (United States)

    Montandon, Gaspard; Horner, Richard L; Kinkead, Richard; Bairam, Aida

    2009-11-15

    Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.

  8. Effect of G-CSF and TPO on HIBD in neonatal rats.

    Science.gov (United States)

    Liu, Xue-Mei; Feng, Yi; Li, Ai-Min

    2015-02-01

    To observe effect of granulocyte colony-stimulating factor (G-CSF) and restructure human thrombopoietin on hypoxic-ischemic brain damage (HIBD) in new born rats. A total of 60 neonatal SD rats were selected and divided into 4 groups, with 15 in each group. Group A served as control group. Rats of Groups B-D were prepared for HIBD model by ligation of left common carotid artery combined with hypoxia method. Rats of Group A were only completed with free left common carotid artery without ligation and hypoxia operation. After HIBD model preparation, Group B was administrated with subcutaneous injection of normal saline for placebo treatment; Group C was administrated with cervical subcutaneous injection of 0.5 μg/10 g granulocyte colony stimulating factor (G-CSF) for 5 d (Once a day); Group D was administrated with intraperitoneal injection of 15 U/10 g recombinant human thromobopoietin (rhTPO) for treatment. After modeling for 7, 14 and 21 d, 5 rats were sacrificed in each group, respectively. Brain quality damage (%) conditions of experimental animals in each group were compared in different time points, and cerebral histopathological changes of each group were observed. Expression of nestin in rats of each group was detected by immunohistochemical method. After modeling for 7, 14 and 21 d, brain quality damages (%) of Groups B, C and D were significant higher than that of in Group A (P0.05). Both G-CSF and TPO can protect the nervous system of HIBD neonatal rats. G-CSF can promote the proliferation and differentiation of neural precursor cells to decrease the degeneration and necrosis of nerve cell. TPO can obviously ameliorate morphology index of HIBD rats. Through regulating ratio of TIMP-1 and MMP-9, TPO can maintain the integrity of blood brain barrier to relieve the occurrence of brain damage. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  9. Neonatal handling affects learning, reversal learning and antioxidant enzymes activities in a sex-specific manner in rats.

    Science.gov (United States)

    Noschang, Cristie; Krolow, Rachel; Arcego, Danusa Mar; Toniazzo, Ana Paula; Huffell, Ana Paula; Dalmaz, Carla

    2012-06-01

    Early life experiences have profound influences on behavior and neurochemical parameters in adult life. The aim of this study is to verify neonatal handling-induced sex specific differences on learning and reversal learning as well as oxidative stress parameters in the prefrontal cortex and striatum of adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth). In adulthood, learning and reversal learning were evaluated using a Y maze associated with palatable food in male and female rats. Morris water maze reversal learning was verified in males. Oxidative stress parameters were evaluated in both genders. Male neonatal handled animals had a worse performance in the Y maze reversal learning compared to non-handled ones and no difference was observed in the water maze reversal learning task. Regarding females, neonatal handled rats had a better performance during the Y maze learning phase compared to non-handled ones. In addition, neonatal handled female animals showed a decreased SOD/CAT ratio in the PFC compared to non-handled females. We conclude that neonatal handling effects on learning and memory in adult rats are sex and task specific. The sex specific differences are also observed in the evaluation of antioxidant enzymes activities with neonatal handling affecting only females. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

  10. Neonatal handling increases sensitivity to acute neurodegeneration in adult rats

    NARCIS (Netherlands)

    Horvath, KM; Harkany, T; Mulder, J; Koolhaas, JM; Luiten, PGM; Meerlo, P

    2004-01-01

    Environmental stimuli during the perinatal period can result in persistent individual differences in neural viability and cognitive functions. Earlier studies have shown that brief daily maternal separation and/or handling of rat pups during the first weeks of life reduces stress reactivity during

  11. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  12. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  13. A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Laura Louise Scott

    2017-12-01

    Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

  14. Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats.

    Science.gov (United States)

    Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

    2013-11-13

    Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

  15. Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

    Science.gov (United States)

    Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

    2018-04-23

    Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

    Science.gov (United States)

    Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation

  17. The effects of X-ray radiation on mandibular bone of low-calcium diet rats

    Energy Technology Data Exchange (ETDEWEB)

    Kurita, Akihiko (Nippon Dental Univ., Tokyo (Japan))

    1991-08-01

    In an attempt to examine the effects of X-ray on osteoporosis, a single dose of 30 Gy was delivered to the mandible in rats given low-calcium diet. Serum levels of calcium (Ca) and inorganic phosphorus (P) were measured; and changes in bone salt were determined by autoradiography, microradiography, and roentgenography using an electron probe microanalyzer. Body weight was lower in the irradiated group than the non-irradiated group, irrespective of types of diet. The serum Ca levels in the irradiated group given a normal diet were significantly decreased on Days 3, 7, and 14 days after irradiation. When given a low-Ca diet, these levels tended to be lower in the irradiated group than the non-irradiated group on Day 7 or later. The serum levels of inorganic P were significantly lower in the irradiated group given a normal diet than the non-irradiated group on Day 3. Rats given a low-Ca diet had the same levels, irrespective of irradiation. Autoradiography revealed that Ca-45 retention in the whole jaw was slightly greater in the irradiated group than the non-irradiated group On Days 7 and 21. Rats given a low-Ca diet in both irradiated and non-irradiated groups had a greater Ca-45 retention than those given a normal diet. Microradiography revealed that bone formation-like changes, such as flat surface of the periodontal membrane at the intra-alveolar septum, were slightly noticeable in the irradiated group of rats given a normal diet on Day 21. Thinning of the intra-alveolar septum and decrease of the trabecula at the diaphysis were also noticeable in the irradiated group of rats given a low-Ca diet. Variation of X-ray intensity was more marked on Day 7 than on Day 21 in the irradiated group given a normal diet. When given a low-Ca diet, both the irradiated and non-irradiated group had noticeable X-ray intensity variation. (N.K.).

  18. Fffects of testosterone propionate on neonatal and prepuberal development of os penis in male rats.

    Science.gov (United States)

    Yoshida, H; Kadota, A; Fukunishi, R

    1980-01-01

    Osteogenesis in the penial bone was observed in male rat: immature stromal cells of mesenchymal origin appeared in the penis on the 21st day of fetal age and developed to form mature bony structure with the bonemarrow on or before day 7 after birth; the bone was 1.41 +/- 0.12 mm in length. Neonatal castration caused maldevelopment of the penial bone, while prepuberal treatment with testosterone propionate stimulated the bony growth in castrated immature rat. These results suggest that the stromal cells in penile part of newborn male rats have already been destinated to develop into os penis by fetal exposure to androgen and they do not require androgens for further differentiation but for the bony growth after birth.

  19. CELECOXIB ATTENUATES SYSTEMIC LIPOPOLYSACCHARIDE-INDUCED BRAIN INFLAMMATION AND WHITE MATTER INJURY IN THE NEONATAL RATS

    Science.gov (United States)

    FAN, L.-W.; KAIZAKI, A.; TIEN, L.-T.; PANG, Y.; TANAKA, S.; NUMAZAWA, S.; BHATT, A. J.; CAI, Z.

    2013-01-01

    Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in postnatal day 5 (P5) of Sprague-Dawley rat pups and celecoxib (20 mg/kg) or vehicle was administered i.p. 5 min after LPS injection. The body weight and wire hanging maneuver test were performed 24 hr after the LPS exposure, and brain injury was examined after these tests. Systemic LPS exposure resulted in an impairment of behavioral performance and acute brain injury, as indicated by apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. Treatments with celecoxib significantly reduced systemic LPS-induced neurobehavioral disturbance and brain damage. Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties. PMID:23485816

  20. Low dietary protein and high carbohydrate infant formula affects the microbial ecology of the large intestine in neonatal rats.

    Science.gov (United States)

    Fan, Wenguang; Ren, Haiwei; Cao, Yingying; Wang, Yonggang; Huo, Guicheng

    2017-12-01

    The aim of this study was to investigate the effects of a low dietary protein and high carbohydrate infant formula on the large intestine of neonatal rats. A total of 24 neonatal Sprague-Dawley rats (14-days-old) were randomly assigned to the low protein, high carbohydrate infant formula-fed group (I group) and a human breast milk-fed group (H group). After 7 days, we selected 6 rats at random from each group to study. No significantly different microbial colonization patterns were observed in the 2 groups at the phylum level. At the family level, Enterobacteriaceae and Bacteroidaceae were the dominant bacteria in I and H rats. While Bacteroides was the most abundant bacteria at the genus level, no significant difference was observed between the 2 groups. Methanoic acid, acetate, and butyrate increased in concentration in the I group compared with the H group. Protease activities, ammonia, and indole in the large intestine were lower in I rats than H rats. A significant increase in the expression of GADPH and decrease in the expression of aquaporin 8, aminopeptidase A, cathepsin F precursor, and ubiquitin carboxyl-terminal hydrolase FAF-Y were observed in I rats compared with H rats. These results suggest that a low protein diet could modulate the microbial ecology in the large intestine of neonatal rats.

  1. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans. Copyright © 2016. Published by Elsevier Ireland Ltd.

  2. KCC2 expression changes in Diazepam-treated neonatal rats with hypoxia-ischaemia brain damage.

    Science.gov (United States)

    Ma, Jun-Yuan; Zhang, Su-Pei; Guo, Liu-Bin; Li, Yong-Mei; Li, Qiang; Wang, Sai-Qi; Liu, Hong-Min; Wang, Cong

    2014-05-14

    Hypoxia-ischaemia brain damage (HIBD) is a major type of perinatal brain injury in newborns. In this study, we investigate the short- and long-term neuroprotective effects of Diazepam on neonatal rats with HIBD and the potential mechanisms underlying its protective effects. Seven-day-old Sprague-Dawley rats were subjected to left carotid artery ligation followed by a 2-h exposure to 8% oxygen and 92% nitrogen. Diazepam was administered immediately via intraperitoneal (i.p.) injection after inducing HIBD at a dose of 10 mg kg(-1)8h(-1) for three consecutive days. Three days after HIBD, rats were decapitated, and the extent of brain injury was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Additionally, the expression of Potassium-chloride cotransporter-2 (KCC2) was analysed using real-time PCR, Western blot analysis and immunohistochemistry. Three weeks after HIBD, rats were subjected to the Morris water maze (MWM) test and the locomotor activity test to determine the long-term therapeutic effects of Diazepam. We observed that the volume of infarction in the Diazepam group was significantly less (PDiazepam rats improved significantly compared with the untreated rats (PDiazepam appears to attenuate HIBD and can efficiently improve the long-term learning and memory capabilities of the animal. A potential mechanism underlying these effects may involve preventing the decrease in KCC2 expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats.

    Science.gov (United States)

    Bian, Zhao-Xiang; Zhang, Man; Han, Quan-Bin; Xu, Hong-Xi; Sung, Joseph J Y

    2010-02-21

    To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms. JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method. NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg), as compared to that of NH rats (57.7 +/- 1.9 mmHg, P serotonin signaling pathway in the colon of rats.

  4. Longitudinal MRI monitoring of brain damage in the neonatal ventral hippocampal lesion rat model of schizophrenia.

    Science.gov (United States)

    Bertrand, Jean-Baptiste; Langlois, Jean-Baptiste; Bégou, Mélina; Volle, Julien; Brun, Philippe; d'Amato, Thierry; Saoud, Mohamed; Suaud-Chagny, Marie-Françoise

    2010-02-01

    Rat with excitotoxic neonatal ventral hippocampal lesions (NVHL rats) is considered as a heuristic neurodevelopmental model for studying schizophrenia. Extensive study of this model is limited by the lack of clear validity criteria of such lesions and because ascertaining of the lesions is realized postmortem with histological examination after completing experiments. Here, in a first experiment, by assessing the locomotor response to amphetamine in adult NVHL rats, we further specify that the lesions must be bilateral and confined to the ventral hippocampus to obtain the validated behavioral phenotype. We then show a longitudinal magnetic resonance imaging (MRI) protocol suitable for the detection of brain structural changes in NVHL rats. The T(2)-weighted images acquired in adult NVHL rats reveal the same structural changes as those appraised with histological protocol. Moreover, we demonstrate that the lesion status in adulthood can be accurately predicted from the T(2)-weighted images acquired in the juvenile period. As technical advantages, our MRI protocol makes possible to select animals according to lesion criteria as soon as in the juvenile period before long-lasting experiments and gives access in vivo to a quantitative parameter indicative of the lesion extent. Finally, we show that the lesion size increases only slightly between juvenile and adult periods. These latter results are discussed in the context of the specific postpubertal emergence of the behavioral deficits in NVHL rats.

  5. Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat

    Science.gov (United States)

    Guo, Zikang; Li, Jiang

    2017-01-01

    Abstract The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells. PMID:29318034

  6. Digestive enzyme expression and epithelial structure of small intestine in neonatal rats after 16 days spaceflight

    Science.gov (United States)

    Miyake, M.; Yamasaki, M.; Hazama, A.; Ijiri, K.; Shimizu, T.

    It is important to assure whether digestive system can develop normally in neonates during spaceflight. Because the small intestine changes its function and structure drastically around weaning known as redifferentiation. Lactase expression declines and sucrase increases in small intestine for digestion of solid food before weaning. In this paper, we compared this enzyme transition and structural development of small intestine in neonatal rats after spaceflight. To find digestive genes differentially expressed in fight rats, DNA membrane macroarray was also used. Eight-day old rats were loaded to Space Shuttle Columbia, and housed in the animal facility for 16 days in space (STS-90, Neurolab mission). Two control groups (AGC; asynchronous ground control and VIV; vivarium) against flight group (FLT) were prepared. There was no difference in structure (crypt depth) and cell differentiation of epithelium between FLT and AGC by immunohistochemical analysis. We found that the amount of sucrase mRNA compared to lactase was decreased in FLT by RT-PCR. It reflected the enzyme transition was inhibited. Increase of 5 genes (APO A-I, APO A-IV, ACE, aFABP and aminopeptidase M) and decrease of carboxypeptidase-D were detected in FLT using macroarray. We think nutrition differences (less nourishment and late weaning) during spaceflight may cause inhibition of enzyme transition at least partly. The weightlessness might contribute to the inhibition through behavioral change.

  7. High-dose erythropoietin inhibits apoptosis and stimulates proliferation in neonatal rat intestine.

    Science.gov (United States)

    McPherson, Ronald J; Juul, Sandra E

    2007-10-01

    Erythropoietin (Epo) receptors are widely expressed in the small bowel of neonatal rats and evidence suggests Epo has important trophic effects in developing bowel. To compliment in vitro data, we directly examine in vivo the hypotheses that systemic Epo treatment can promote cell division and enterocyte migration, and arrest apoptosis in the ileum of neonatal rats. Epo (5000 U/kg s.c.) or vehicle treatments were given to one week old Sprague-Dawley rats (n = 86) along with timed injections of the thymidine analog 5-bromo-2-deoxyuridine (BrdU, 50mg/kg s.c.) to label DNA synthesis and track newly proliferating cells. To characterize the time course of effects, animals were killed at scheduled times from 30 min to 24 h after treatment. BrdU-containing cells were immunostained and counted in intestinal crypts, villi, and muscle wall of ileum. Effects of Epo on apoptosis were analyzed by TUNEL staining. Calibrated measurements were made to determine the density or relative proportion of BrdU- and TUNEL-positive cells. Systemic high-dose Epo promoted cell division in intestinal smooth muscle and enterocytes, stimulated migration of intestinal epithelial cells, and arrested apoptosis of enterocytes at the villous tips. These data provide in vivo evidence that Epo functions trophically in developing intestine tissues.

  8. Feeding Vitamin C during Neonatal and Juvenile Growth Improves Learning and Memory of Rats.

    Science.gov (United States)

    Hosseini, Mahmoud; Beheshti, Farimah; Sohrabi, Farzaneh; Vafaee, Farzaneh; Shafei, Mohammad Naser; Reza Sadeghnia, Hamid

    2017-11-27

    We investigated the effects of feeding vitamin C (Vit C) during neonatal and juvenile growth on learning and memory of rats. Rats after delivery were randomly divided into four groups and treated. Group 1, control group, received normal drinking water. Groups 2-4 received Vit C 10, 100, and 500 mg/kg, respectively, from the first day. After 8 weeks, 10 male offspring of each group were randomly selected and tested in the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical measurement. In MWM, 10-500 mg/kg Vit C reduced the latency and traveled distance and increased time spent in the target quadrant. In PA, 10 and 100 mg/kg of Vit C increased the latency; 10-500 mg/kg of Vit C decreased the malondialdehyde (MDA) in the brain tissues and increased thiol and catalase (CAT) activity compared to the control group. We showed that feeding rats Vit C during neonatal and juvenile growth has positive effects on learning and memory.

  9. Impact of neonatal NOS-1 inhibitor exposure on neurobehavioural measures and prefrontal-temporolimbic integration in the rat nucleus accumbens.

    Science.gov (United States)

    Dec, Alexander M; Kohlhaas, Kathy L; Nelson, Christopher L; Hoque, Kristina E; Leilabadi, Solmaz N; Folk, Jessica; Wolf, Marina E; West, Anthony R

    2014-02-01

    Nitric oxide (NO) is a gaseous neurotransmitter that plays a significant role in the establishment and refinement of functional neural circuits. Genetic and post-mortem studies have suggested that neuronal NO synthase (NOS-1) activity may be compromised in frontal and temporal lobes, and related structures, in schizophrenia. The goal of this study was to determine if there is a link between neonatal disruptions in NO signalling and disturbances in the development and function of prefrontal-temporolimbic circuits. Neonatal rats were injected on postnatal days PD3-5 with the selective NOS-1 inhibitor Nω-propyl-L-arginine (NPA) and tested in adulthood (≥PD60) or as juveniles (PD30). Adult rats treated with NPA as neonates exhibited increased amphetamine-induced locomotion compared to animals receiving vehicle as neonates, whereas this was not observed in juvenile rats treated with NPA as neonates. Adult rats exposed to NPA as neonates also exhibited deficits in social interaction and short-term recognition memory, as well as reduced brain weight, compared to vehicle-treated controls. Finally, neonatal NPA exposure increased the responsiveness of nucleus accumbens neurons to prefrontal cortical input and disrupted the modulation of cortico-accumbens circuits by hippocampal afferents that is normally observed in adult animals. These results show for the first time that neonatal inhibition of NOS-1 during a critical neurodevelopmental period leads to aberrant behaviours that manifest in adulthood, as well as electrophysiological abnormalities in prefrontal-temporolimbic circuits. Greater understanding of the role of NOS-1 in the development of these circuits will shed light on how developmental insults translate to pathophysiology associated with schizophrenia.

  10. Long-term cognitive impairments in adult rats treated neonatally with beta-N-Methylamino-L-Alanine

    OpenAIRE

    Karlsson, Oskar; Roman, Erika; Brittebo, Eva B.

    2009-01-01

    Most cyanobacteria (blue-green algae) can produce the neurotoxin beta-N-methylamino-L-alanine (BMAA). Dietary exposure to BMAA has been suggested to be involved in the etiology of the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC). Little is known about BMAA-induced neurotoxicity following neonatal administration. Our previous studies have revealed an uptake of BMAA in the hippocampus and striatum of neonatal mice. Furthermore, rats treated wit...

  11. Study on developing brain damage of neonatal rats induced by enriched uranium

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Yang Shuqin

    2000-01-01

    Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

  12. Effect of erythropoietin on intestinal injury and bacterial translocation in neonatal rat model of necrotizing enterocolitis

    Directory of Open Access Journals (Sweden)

    Xiao-qing CHEN

    2012-05-01

    Full Text Available Objective  To observe the influence of erythropoietin (EPO on intestinal histopathological changes and bacterial translocation (BT in neonatal rat model of necrotizing enterocolitis (NEC, and explore the protective effect of EPO against NEC. Methods  Seventy-five three-day-old SD rat pups were randomly divided into three groups (25 in each group: normal control group, NEC model group and EPO intervention group. The rat pups in normal control group were placed together with their mothers and breast fed, receiving no other intervention. NEC model group rats were separated from their mothers, housed in an incubator, and gavaged with rat-milk substitute, then experienced hypoxia (breathing 100% nitrogen gas for 90s and cold stress (4℃ for 10min three times daily for 3 days. EPO intervention group rats were fed with the substitute of rat-milk supplemented with 0.1U/ml of EPO, and they were also given hypoxia and cold stress similar to that of the NEC model group. Blood samples were obtained via cardiac puncture, and 2-cm-length of terminal ileum proximal to the ileocecal valve were obtained from the animals on the 4th day. The histopathological changes in terminal ileum were scored after hematoxylin-eosin (HE staining, and the scores ≥2 were defined as NEC. To determine the incidence of bacterial translocation, 16S rRNA real-time fluorescence quantitative PCR was used to detect the bacterial DNA in blood samples. Results  Compared with the NEC model group, the mean rank-sum rate of the intestinal histopathological score (39.4583 vs 53.8696, NEC incidence [25%(6/24 vs 57%(13/23] and bacterial translocation rate [17% (4/24 vs 65%(15/23] in EPO intervention group were significantly lowered (P < 0.05, P < 0.01. Conclusion  Enteral EPO administration is not only effective for reduction of the severity and incidence of NEC, but also for decrease of the bacterial translocation rate in neonatal rat models.

  13. Expression of aquaporin 9 in rat liver and efferent ducts of the male reproductive system after neonatal diethylstilbestrol exposure

    DEFF Research Database (Denmark)

    Wellejus, Anja; Jensen, Henrik E; Loft, Steffen

    2008-01-01

    Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from day...... to the epithelial cells of the ED. In conclusion, neonatal DES exposure appears to upregulate AQP9 channels in the ED in male rats, whereas a downregulation in the hepatic expression was observed, particularly in the periacinous area....

  14. In vitro study of acetylcholine and histamine induced contractions in colon and rectum of adult and neonate rats.

    Science.gov (United States)

    Singh, Shuchita; Mandal, Maloy B

    2013-01-01

    Contractile mechanisms of different parts of the gut in adult and neonate may not be identical due to developmental processes. The present study was undertaken to investigate acetylcholine (ACh) and histamine induced contractile responses of colon and rectum in adult and neonatal albino rats. Contractile responses were recorded from isolated in vitro preparations. The dose-response curve for ACh (0.001-100 microM) revealed dose dependent increase in contractile responses. A significantly (P pheniramine (100 microM) in adult rectum. This potentiating response of pheniramine was absent in neonate rectum. Such effect was also not seen in colon of both adult and neonate. The present investigation indicates that the contractile responses induced by ACh are similar in both adult and neonate, excepting that the blocking effect of atropine in colon was more pronounced in adult as compared to neonate. Further, the results also indicated different mechanism of histamine action in adults and neonates as evidenced by the significant enhancement of contractions by pheniramine only in adult rectum. Therefore, the present results indicate the existence of a different cholinergic and histaminergic activity in adult and neonate as well as in rectal and colonic tissue.

  15. Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

    Directory of Open Access Journals (Sweden)

    Guy eSandner

    2014-01-01

    Full Text Available Rats with a neonatal ventral hippocampal lesion (NVHL are used to model schizophrenia. They show enhanced locomotion and difficulties in learning after puberty. Such behavioural modifications are strengthened by dopaminergic psychostimulant drugs, which is also relevant for schizophrenia because illustrating its dopaminergic facet. But it remains questionable that only dopaminergic drugs elicit such effects. The behavioural effects could simply represent a non specific arousal, in which case NVHL rats should also be hyper-responsive to other vigilance enhancing drugs. We administered an adenosine (caffeine or an adrenaline receptor antagonist, (RX821002 at doses documented to modify alertness of rats, respectively 5 mg/Kg and 1 mg/Kg. Rats were selected prior to the experiments using MRI (magnetic resonance imaging. Each group contained typical and similar NVHL lesions. They were compared to sham lesioned rats. We evaluated locomotion in a new environment and the capacity to remember a visual or acoustic cue that announced the occurrence of food. Both Caffeine and RX82100 enhanced locomotion in the novel environment, particularly in NVHL rats. But, RX82100 had a biphasic effect on locomotion, consisting of an initial reduction preceding the enhancement. It was independent of the lesion. Caffeine did not modify the learning performance of NVHL rats. But, RX821002 was found to facilitate learning.Patients tend to intake much more caffeine than healthy people, which has been interpreted as a means to counter some cognitive deficits. This idea was not validated with the present results. But adrenergic drugs could be helpful for attenuating some of their cognitive deficits.

  16. Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia.

    Science.gov (United States)

    Bavis, Ryan W; Li, Ke-Yong; DeAngelis, Kathryn J; March, Ryan J; Wallace, Josefine A; Logan, Sarah; Putnam, Robert W

    2017-03-01

    Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO 2 /pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O 2 (Control) or 60% O 2 (Hyperoxia) until studied at 4, 6-7, or 13-14days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO 2 at all ages; CO 2 sensitivity recovered within 7days after return to room air. Hypercapnic responses of CO 2 -sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO 2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Effects of sleeve gastrectomy in neonatally streptozotocin-induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available BACKGROUND: Sleeve gastrectomy (SG has emerged recently as a stand-alone bariatric procedure to treat morbid obesity and enhance glucose homeostasis. The aim of the study was to evaluate its effects in neonatally streptozotocin (STZ-induced diabetic rats (n-STZ diabetic rats. METHODOLOGY AND PRINCIPAL FINDINGS: To induce diabetes, STZ (90 mg/kg was administered intraperitoneally to 2-day-old male pups. When 12 weeks old, diabetic rats were randomized into sleeve operation group (SLG, n = 6 and sham operation group (SOG, n = 6. Body weights were monitored weekly, and daily consumption of water and food were followed for eight consecutive weeks postoperatively. Serum glucose levels were measured periodically at the 4th and 8th week after surgery. Insulin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP and Glucagon-like peptide-1 (GLP-1 levels were assayed at the end of the study. Our data showed that SLG rats exhibited significantly lower body weight gain in addition to reduced food and water intakes postoperatively compared to their sham-operation counterparts. However, resolution of diabetes was not observed in our study. Correspondingly, there were no significant differences between SOG rats and SLG rats in glucose metabolism-associated hormones, including insulin, GIP and GLP-1. In contrast, ghrelin level significantly decreased (P<0.01 in SLG group (58.01 ± 3.75 pg/ml after SG surgery compared to SOG group (76.36 ± 3.51 pg/ml. CONCLUSIONS: These observations strongly suggest that SG is effective in controlling body weight. However, SG did not achieve resolution or improvement of diabetes in n-STZ diabetic rats.

  18. Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic-ischemic rats.

    Science.gov (United States)

    Greggio, Samuel; de Paula, Simone; Azevedo, Pâmella Nunes; Venturin, Gianina Teribele; Dacosta, Jaderson Costa

    2014-02-06

    Based on preclinical findings, cellular therapy has become a promising therapeutic approach for neonatal hypoxia-ischemia (HI). However, before translation into the clinical setting, new and effective routes of cell delivery must be determined. Intra-arterial (IA) delivery is an attractive route of cellular administration but has never been used in neonatal HI rats. In this study, we investigated the feasibility of IA transplantation of human umbilical cord blood (HUCB) mononuclear cells for the treatment of long-term behavior dysfunction and brain lesion after neonatal HI. Seven-day-old rats were subjected to a HI model and the animals received HUCB mononuclear cells into the left common carotid artery 24 h after HI insult. At 9 weeks post-HI, intra-arterially transplanted HUCB mononuclear cells significantly improved learning and long-term spatial memory impairments when evaluated by the Morris water maze paradigm. There was no effect of neonatal HI insult or IA procedure on body weight and on motor coordination and balance when evaluated by the accelerating rotarod test. Cellular transplantation by the IA route did not restore neonatal HI-induced brain damage according to stereological volume assessment. Furthermore, HUCB mononuclear cells were tracked in the injured brain and peripheral organs of HI transplanted-rats by nested polymerase chain reaction analysis at different time points. Our findings contribute to the translational knowledge of cell based-therapy in neonatal HI and demonstrate for the first time that IA transplantation into rat pups is a feasible route for cellular delivery and prevents long-term cognitive deficits induced by experimental neonatal HI. © 2013.

  19. Changes in the expression of aromatase, estrogen receptor α and β in mandibular condylar cartilage of rats induced by disordered occlusion

    Directory of Open Access Journals (Sweden)

    Yu Shibin

    2012-09-01

    Full Text Available Abstract Background Estrogens play an important role in modulating the morphology and function of temporomandibular joints (TMJs, which is suggested to act via estrogen receptors (ERs. The present study was to investigate the expression of aggrecan, collagen type II (Col II, Col X, aromatase, ERα and ERβ in degenerative changes of mandibular condylar cartilage. Methods Forty male and 40 female 8-week-old rats were enrolled in this study. In experimental groups, the disordered occlusion was created by moving the first molars mesially and the third ones distally. Immunohistochemistry and real-time PCR were performed at the end of the second or fourth week. Results Degenerative changes, characterized by interrupted continuity of hypertrophic layer, pyknotic and eosinophilic lesion with few nuclei, areas filled with eosinophilic nuclei, were observed in more joints from female experimental groups than male ones. However, thickening changes in hypertrophic layer were only found in male experimental groups. The gene expression of Col II, Col X and aggrecan increased in 4-wk male experimental subgroup (both P Conclusions Mandibular condylar cartilage responses differently to the disordered occlusion in male and female rats. The levels of locally synthesized estrogen, ERα and ERβ may have limited attribution, if any, to the sex-specific cartilage response.

  20. A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current.

    Directory of Open Access Journals (Sweden)

    Rupamanjari Majumder

    2016-06-01

    Full Text Available Atrial fibrillation (AF is the most frequent form of arrhythmia occurring in the industrialized world. Because of its complex nature, each identified form of AF requires specialized treatment. Thus, an in-depth understanding of the bases of these arrhythmias is essential for therapeutic development. A variety of experimental studies aimed at understanding the mechanisms of AF are performed using primary cultures of neonatal rat atrial cardiomyocytes (NRAMs. Previously, we have shown that the distinct advantage of NRAM cultures is that they allow standardized, systematic, robust re-entry induction in the presence of a constitutively-active acetylcholine-mediated K+ current (IKACh-c. Experimental studies dedicated to mechanistic explorations of AF, using these cultures, often use computer models for detailed electrophysiological investigations. However, currently, no mathematical model for NRAMs is available. Therefore, in the present study we propose the first model for the action potential (AP of a NRAM with constitutively-active acetylcholine-mediated K+ current (IKACh-c. The descriptions of the ionic currents were based on patch-clamp data obtained from neonatal rats. Our monolayer model closely mimics the action potential duration (APD restitution and conduction velocity (CV restitution curves presented in our previous in vitro studies. In addition, the model reproduces the experimentally observed dynamics of spiral wave rotation, in the absence and in the presence of drug interventions, and in the presence of localized myofibroblast heterogeneities.

  1. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Prostanoid Receptors Involved in Regulation of the Beating Rate of Neonatal Rat Cardiomyocytes

    Science.gov (United States)

    Mechiche, Hakima; Grassin-Delyle, Stanislas; Robinet, Arnaud; Nazeyrollas, Pierre; Devillier, Philippe

    2012-01-01

    Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PG)F2α and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol) produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD2 and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP1 and EP3 receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP1 antagonist). Butaprost (a selective prostanoid EP2 receptor agonist), misoprostol (a prostanoid EP2 and EP3 receptor agonist), 11-deoxy-PGE1 (a prostanoid EP2, EP3 and EP4 receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP1 receptors are involved in positive regulation of the beating rate. Prostanoid EP1 receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate) and prostanoid TP, DP1 and EP1 receptors (which positively regulate the spontaneous beating rate). PMID:22984630

  3. Distribution and retention of organic and inorganic mercury in methyl mercury-treated neonatal rats

    International Nuclear Information System (INIS)

    Thomas, D.J.; Fisher, H.L.; Sumler, M.R.; Hall, L.L.; Mushak, P.

    1988-01-01

    Seven-day-old Long Evans rats received one mumol of 203 Hg-labeled methyl mercury/kg sc and whole body retention and tissue distribution of organic and inorganic mercury were examined for 32 days postdosing. Neonates cleared mercury slowly until 10 days postdosing when the clearance rate abruptly increased. During the interval when whole body clearance of mercury was extremely slow, methyl mercury was metabolized to inorganic mercury. Peak concentration of mercury in kidney occurred at 2 days postdosing. At 32 days postdosing, 8% of mercury in kidney was in an organic from. Liver mercury concentration peaked at 2 days postdosing and organic mercury accounted for 38% at 32 days postdosing. Brain concentrations of mercury peaked at 2 days postdosing. At 10 days postdosing, organic mercury accounted for 86% of the brain mercury burden, and, at 32 days postdosing, for 60%. The percentage of mercury body burden in pelt rose from 30 to 70% between 1 and 10 days postdosing. At 32 days postdosing pelt contained 85% of the body burden of mercury. At all time points, about 95% of mercury in pelt was in an organic form. Compartmental analysis of these data permitted development of a model to describe the distribution and excretion of organic and inorganic mercury in methyl mercury-treated neonatal rats

  4. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats

    DEFF Research Database (Denmark)

    Secher, Thomas; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    , including cognitive impairment relevant to schizophrenia. The present study investigated the effect of FGL on spatial learning and memory deficits induced by neonatal PCP treatment. Rat pups were treated with 30mg/kg PCP on postnatal days 7, 9, and 11. Additionally, the rats were subjected to a chronic FGL...... treatment regimen where FGL was administered throughout development. Rats were tested as adults for spatial reference memory, reversal learning, and working memory in the Morris water maze. The PCP-treated rats demonstrated a robust impairment in working memory and reversal learning. However, the long......-term memory component of the reference memory task was not affected by PCP. Chronic FGL treatment had no effect on the reversal learning impairment but ameliorated the working memory deficits almost to the levels of the control groups. In conclusion, the results suggest that the neonatal PCP treatment...

  5. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

    Directory of Open Access Journals (Sweden)

    Nicolas Martin

    Full Text Available Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence. We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  6. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

    Science.gov (United States)

    Martin, Nicolas; Bossenmeyer-Pourié, Carine; Koziel, Violette; Jazi, Rozat; Audonnet, Sandra; Vert, Paul; Guéant, Jean-Louis; Daval, Jean-Luc; Pourié, Grégory

    2012-01-01

    Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  7. Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Jeffers, Matthew Strider; Antonescu, Sabina; Nguemeni, Carine; Gomez-Smith, Mariana; Pereira, Lenir Orlandi; Morshead, Cindi M; Corbett, Dale

    2016-05-01

    Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main

  8. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

    Directory of Open Access Journals (Sweden)

    Yuri Karen Sinzato

    2012-01-01

    Full Text Available The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously. At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women.

  9. Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction.

    Science.gov (United States)

    Ingaramo, Paola I; Varayoud, Jorgelina; Milesi, María M; Schimpf, Marlise Guerrero; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2016-11-01

    In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss. © 2016 Society for Reproduction and Fertility.

  10. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

    Directory of Open Access Journals (Sweden)

    Madhoosudan A. Patil

    2014-01-01

    Full Text Available Type 2 diabetes (T2D generally follows prediabetes (PD conditions such as impaired fasting glucose (IFG and/or impaired glucose tolerance (IGT. Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70% of nSTZ injected pups developed IGT (nSTZ-PD by two months but not cataract even after seven months, remaining (30% nSTZ rats developed hyperglycemia (nSTZ-D by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.

  11. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  12. Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2017-01-01

    Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson's disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently...... reported that neonatal hRPE cells, similar to hRPE cells used in the Phase II clinical study, produced short-lived in vitro and limited in vivo trophic factors, which supports that assumption. We hypothesize that the switch from fetal to neonatal hRPE cells, between the Phase I and the Phase II clinical...... following unilateral striatal implantation in 6-hydroxydopamine-lesioned rats. The results showed that only fetal, not neonatal, hRPE cell implants, were able to improve behavioral outcomes following striatal implantation in the lesioned rats. These data suggest that fetal hRPE cells may be preferential...

  13. The effects of capsaicin and acidity on currents generated by noxious heat in cultured neonatal rat dorsal root ganglion neurones

    Czech Academy of Sciences Publication Activity Database

    Vlachová, Viktorie; Lyfenko, Alla; Orkand, R. K.; Vyklický st., Ladislav

    2001-01-01

    Roč. 533, č. 3 (2001), s. 717-728 ISSN 0022-3751 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin * dorsal root ganglion neurones * neonatal rat Subject RIV: FH - Neurology Impact factor: 4.476, year: 2001

  14. ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

    Czech Academy of Sciences Publication Activity Database

    Rakusan, K.; Chvojková, Zuzana; Oliviero, P.; Ošťádalová, Ivana; Kolář, František; Chassagne, C.; Samuel, J. L.; Ošťádal, Bohuslav

    2007-01-01

    Roč. 292, č. 3 (2007), H1237-H1244 ISSN 0363-6135 R&D Projects: GA MŠk 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : angiogenesis neonatal rat * ANG II type 1 receptor antagonist heart * ischemic tolerance Subject RIV: ED - Physiology Impact factor: 3.973, year: 2007

  15. Anionic and cationic drug secretion in the isolated perfused rat kidney after neonatal surgical induction of ureteric obstruction.

    NARCIS (Netherlands)

    Gier, R.P.E. de; Feitz, W.F.J.; Masereeuw, R.; Wouterse, A.C.; Smits, D.; Russel, F.G.M.

    2003-01-01

    OBJECTIVE: To study the pathophysiological changes of renal tubular drug transport mechanisms in congenital renal obstruction, by developing a model for perfusing the isolated kidney (IPK) after neonatal surgical induction of partial ureteric obstruction in Hanover Wistar rats. MATERIAL AND METHODS:

  16. Maternal low protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring

    Science.gov (United States)

    Prenatal exposure to a maternal low protein diet has been known to cause cognitive impairment, learning and memory deficits. However, the underlying mechanisms have not been identified. Herein, we demonstrate that a maternal low protein (LP) diet causes, in the brains of the neonatal rat offspring, ...

  17. Acute desensitization of presynaptic GABA(B)-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus

    NARCIS (Netherlands)

    Tosetti, P; Bakels, R; Colin-Le Brun, [No Value; Ferrand, N; Gaiarsa, JL; Caillard, O

    The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release

  18. Development of the adult-type Leydig cell population in the rat is affected by neonatal thyroid hormone levels

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; de Jong, F. H.; van Haaster, L. H.

    1998-01-01

    We have investigated the effects of neonatal-prepubertal changes in thyroid hormone levels on the early phases of adult-type Leydig cell development in the rat testis. Hypothyroidism was induced by adding 6-propyl-2-thiouracil (PTU) to the drinking water, while hyperthyroidism was induced by daily

  19. Histopathological Changes of the Heart After Neonatal Dexamethasone Treatment : Studies in 4-, 8-, and 50-Week-Old Rats

    NARCIS (Netherlands)

    Bal, Miriam P.; de Vries, Willem B.; Steendijk, Paul; Homoet-van der Kraak, Petra; van der Leij, Feike R.; van Oosterhout, Matthijs F. M.; van Bel, Frank; Baan, J.

    Dexamethasone (Dex), for prevention of chronic lung disease in preterm infants, showed potential negative long-term effects. Studies regarding long-term cardiovascular effects are lacking. We investigated possible histopathological myocardial changes after neonatal Dex in the young and adult rat

  20. [Effect of AP-1 decoy oligodeoxynucleotides on neonatal rat cardiac fibroblast proliferation and collagen synthesis].

    Science.gov (United States)

    Xie, Shuang-lun; Wang, Jing-feng; Nie, Ru-qiong; Yuan, Wo-liang; Li, Fei; Lin, Mao-huan

    2008-05-01

    To investigate the inhibitory effects of AP-1 decoy oligodeoxynucleotides (ODNs) on angiotensin II (AngII)-induced proliferation and collagen synthesis in neonatal rat cardiac fibroblasts (CFs). The CFs of neonatal SD rats were cultured in serum-free medium for 24 h and stimulated with 10(-7) mol/L AngII in the presence of AP-1 decoy ODNs or mutational AP-1 decoy ODNs at varied concentrations. MTT assay was employed for quantitative evaluation of the CF proliferation. Collagen synthesis in the CFs was assessed with hydroxyproline, and the cell cycle distribution determined with flow cytometry (FCM). With the increase of the concentration of AP-1 decoy ODNs, the absorbance at 490 nm (OD490) of the CFs decreased gradually as shown by MTT assay. Treatment with 100 or 200 nmol/L AP-1 decoy ODNs resulted in significantly lowered OD490 of the CFs as compared with that of AngII group. The concentration of hydroxyproline increased significantly after treatment with 10(-7) mol/L AngII in comparison with the control group (P<0.05). Hydroxyproline concentration in cells treated with 100 or 200 nmol/L AP-1 decoy ODNs was significantly lower than that in the 10(-7) mol/L AngII-treated cells. AP-1 decoy ODNs decreased the cell percentage in S phase and increased hydroxyproline concentration, but increased the percentage of cells in G0/G1 phase. AP-1 decoy ODNs at 100 and 200 nmol/L did not obviously affect AngII-induced CF proliferation and collagen synthesis (P<0.01). AP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.

  1. Transforming growth factor-betas in a rat model of neonatal posthaemorrhagic hydrocephalus.

    Science.gov (United States)

    Cherian, S; Thoresen, M; Silver, I A; Whitelaw, A; Love, S

    2004-12-01

    Posthaemorrhagic ventricular dilatation (PHVD) is a common complication of intraventricular haemorrhage in premature infants. The aim of this study was to investigate the role of transforming growth factor-betas (TGF-betas), a family of polypeptides with potent desmoplastic properties, in the aetiology of PHVD in a newly developed neonatal rat model of this disorder. Pups were injected with citrated rat blood or artificial cerebrospinal fluid (ACSF) into alternate lateral ventricles on postnatal days 7 and 8. The brains were perfusion-fixed 14 days later and immunohistochemistry was performed for TGF-beta1, -beta2 and -beta3, p44/42 mitogen-activated protein (MAP) kinases, and the extracellular matrix proteins laminin, vitronectin and fibronectin. Ventricular dilatation occurred in 58.3% of animals injected with blood and 36.7% of those injected with ACSF. Periventricular immunoreactivity for TGF-beta1 and -beta2 increased in injected animals irrespective of the presence or absence of ventricular dilatation, although the levels of both isoforms tended to be higher in animals with hydrocephalus. TGF-beta3 immunoreactivity was elevated in hydrocephalic rats only. The immunolabelling for phosphorylated p44/42 MAP kinases rose in a pattern similar to that for TGF-beta1 and -beta2. Expression of TGF-betas was accompanied by deposition of the extracellular matrix proteins fibronectin, laminin and vitronectin. The changes caused by injection of ACSF were the same as those caused by injection of blood. Our results raise the possibility that expression of TGF-betas, together with extracellular matrix protein deposition, may be involved in the development and/or maintenance of hydrocephalus after ventricular distension due to haemorrhage in the neonate.

  2. Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory.

    Science.gov (United States)

    Takada, S H; dos Santos Haemmerle, C A; Motta-Teixeira, L C; Machado-Nils, A V; Lee, V Y; Takase, L F; Cruz-Rizzolo, R J; Kihara, A H; Xavier, G F; Watanabe, I-S; Nogueira, M I

    2015-01-22

    Neonatal anoxia in rodents has been used to understand brain changes and cognitive dysfunction following asphyxia. This study investigated the time-course of cellular and subcellular changes and hippocampal cell death in a non-invasive model of anoxia in neonatal rats, using Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) to reveal DNA fragmentation, Fluoro-Jade® B (FJB) to show degenerating neurons, cleaved caspase-3 immunohistochemistry (IHC) to detect cells undergoing apoptosis, and transmission electron microscopy (TEM) to reveal fine ultrastructural changes related to cell death. Anoxia was induced by exposing postnatal day 1 (P1) pups to a flow of 100% gaseous nitrogen for 25 min in a chamber maintained at 37 °C. Control rats were similarly exposed to this chamber but with air flow instead of nitrogen. Brain changes following anoxia were evaluated at postnatal days 2, 14, 21 and 60 (P2, P14, P21 and P60). In addition, spatial reference memory following anoxia and control treatments was evaluated in the Morris water maze, starting at P60. Compared to their respective controls, P2 anoxic rats exhibited (1) higher TUNEL labeling in cornus ammonis (CA) 1 and the dentate gyrus (DG), (2) higher FJB-positive cells in the CA2-3, and (3) somato-dendritic swelling, mitochondrial injury and chromatin condensation in irregular bodies, as well as other subcellular features indicating apoptosis, necrosis, autophagy and excitotoxicity in the CA1, CA2-3 and DG, as revealed by TEM. At P14, P21 and P60, both groups showed small numbers of TUNEL-positive and FJB-positive cells. Stereological analysis at P2, P14, P21 and P60 revealed a lack of significant differences in cleaved caspase-3 IHC between anoxic and control subjects. These results suggest that the type of hippocampal cell death following neonatal anoxia is likely independent of caspase-3 activation. Neonatal anoxia induced deficits in acquisition and performance of spatial reference

  3. Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus.

    Science.gov (United States)

    Guerrero Schimpf, Marlise; Milesi, María M; Ingaramo, Paola I; Luque, Enrique H; Varayoud, Jorgelina

    2017-02-01

    Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2mg/kg) by sc injection every 48h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic differentiation. PR and Hoxa10 were deregulated both immediately and two weeks after the exposure. ERα was induced in the stromal compartment on PND8, and was downregulated in the luminal epithelial cells of gyphosate-exposed animals on PND21. GBH treatment also increased

  4. Effects of benzo(a)pyrene exposure on the ATPase activity and calcium concentration in the hippocampus of neonatal rats.

    Science.gov (United States)

    Yang, Kai; Chen, Chengzhi; Cheng, Shuqun; Cao, Xianqing; Tu, Baijie

    2017-03-30

    To investigate whether postnatal benzo(a)pyrene (B(a)P) exposure caused the impairments on the process of neurodevelopment and the alteration in the calcium medium in the neonatal rats. Eighty neonatal Sprague Dawley (SD) rats were randomly divided into 5 groups (untreated control group, vehicle group, 0.02 mg/kg, 0.2 mg/kg and 2 mg/kg B(a)P-exposed group). Rats were treated with B(a)P by the intragastric administration from postnatal day (PND) 4 to 25. Morris water maze (MWM) was employed to observe the spatial memory of rats. The activity of calcium adenosine triphosphatase (Ca2+-ATPase), sodium-potassium adenosine triphosphatase (Na+-K+-ATPase) and calcium-magnesium adenosine triphosphatase (Ca2+-Mg2+-ATPase) in the hippocampus were detected by commercial kits. Fura-2 pentakis(acetoxymethyl) (Fura-2/AM) probe and reactive oxygen species (ROS) reagent kit were used for measuring the concentration of Ca2+ and ROS in the hippocampus synapse, respectively. Rats exposed to B(a)P resulted in the deficits in the spatial memory manifested by the increased escape latency and decreased number of crossing platform and time spent in target quadrant in comparison with the control groups. Benzo(a)pyrene exposure caused the significant decrease in the ATPase activity in the hippocampus and caused Ca2+ overload in the synaptic, besides, the ROS concentration increased significantly which may further induce neurobehavioral impairment of the neonatal rats. Our findings suggest that postnatal B(a)P exposure may cause the neurobehavioral impairments in the neonatal rats, which were mediated by the decreased ATPase activity and elevated Ca2+ concentration. Int J Occup Med Environ Health 2017;30(2):203-211. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  5. Rat fetuin: distribution of protein and mRNA in embryonic and neonatal rat tissues

    DEFF Research Database (Denmark)

    Terkelsen, O B; Jahnen-Dechent, W; Nielsen, Henrik

    1998-01-01

    functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375...... protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ...... hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E16...

  6. [Protective effect of prostaglandin E1 against brain injury induced by hyperoxia in neonatal rats].

    Science.gov (United States)

    Yang, Shan; Zhang, You-Chen; Li, Hui-Wen; Jin, Zheng-Yong

    2018-03-01

    To investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia. Sixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group. All rats except those in the air control group were treated to establish a hyperoxic brain injury model. From the first day of modeling, the rats in the hyperoxia brain injury+PGE-1 group were intraperitoneally injected with PGE-1 2 μg/kg daily for 7 consecutive days, while the other two groups were treated with normal saline instead. The water content of brain tissue was measured; the pathological changes of brain tissue were evaluated by hematoxylin-eosin staining; the apoptosis of brain cells was assessed by nuclear staining combined with TUNEL staining; the protein expression of GRP78 and CHOP in brain tissue was measured by Western blot. The water content of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the water content of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P<0.05). The pathological section of brain tissue showed inflammatory cell infiltration and mild cerebrovascular edema in the brain parenchyma in the hyperoxic brain injury model group; the periparenchymal inflammation and edema in the hyperoxic brain injury+PGE-1 group were milder than those in the hyperoxic brain injury model group. The apoptosis index of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the

  7. Effect of neonatal capsaicin treatment on orthodontic tooth movement in male Sprague-Dawley rats.

    Science.gov (United States)

    Davila, Julian E; Miller, James R; Hodges, James S; Beyer, John P; Larson, Brent E

    2011-04-01

    In this study, we examined the effect of neonatal administration of capsaicin on the magnitude of orthodontic tooth movement in rats. Twelve timed pregnant Sprague-Dawley rats were randomized between the capsaicin group and the vehicle group. The pups received treatment with either capsaicin or vehicle on day 2 of life. Capsaicin treatment has been shown to produce a selective destruction of fine myelinated and unmyelinated Aδ and C sensory nerve fibers, causing an inhibition of the effects from neurogenic inflammation. Tooth-movement experiments began at 12 weeks of age. A mesial tipping force was applied to the maxillary first molar by using a 3-mm length of Sentalloy closed-coil spring (Dentsply GAC Intl, Bohemia, NY) activated from a bonded molar cleat to the maxillary incisors; this appliance delivers a constant tipping force of 50 g. Diastema measurements between the first and second molars were made at 2 and 4 weeks after appliance placement. Measurements were made indirectly from stone models by using a charge-coupled device microscope camera and Optimas 5.2 measurement software (Media Cybernetics, Bethesda, Md). Two-way repeated-measures analysis of variance (ANOVA) was used to analyze the differences between the groups. The capsaicin-treated rats and the controls did not differ in the amount of tooth movement at the collected time points (P >0.05). Similarly, the magnitude of change of tooth movement from 2 to 4 weeks did not differ between the groups (P >0.05). An increase in average diastema size was observed between 2 and 4 weeks after appliance activation in both treatment groups (P <0.0001). These results suggest that neonatal capsaicin desensitization in the rat does not affect the rate of orthodontic tooth movement after the application of a 50-g tipping force to the maxillary first molar. This might be due in part to the development of compensatory mechanisms in the chronically desensitized rat. Further studies are necessary to determine the

  8. Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in neonatal rats

    Science.gov (United States)

    Ventola, Hanna; Lehtoranta, Liisa; Madetoja, Mari; Simonen-Tikka, Marja-Leena; Maunula, Leena; Roivainen, Merja; Korpela, Riitta; Holma, Reetta

    2012-01-01

    AIM: To study the effects of live and dead Lactobacillus rhamnosus GG (GG) on rotavirus infection in a neonatal rat model. METHODS: At the age of 2 d, suckling Lewis rat pups were supplemented with either live or dead GG and the treatment was continued daily throughout the experiment. At the age of 5 and 6 d the pups received oral rotavirus (RV) SA-11 strain. The pups were sacrificed at the age of 7 or 8 d by decapitation. The gastrointestinal tract was removed and macroscopic observations were done. The consistency of feces in the colon was classified using a four-tier system. RV was detected from the plasma, small intestine, colon and feces by real-time quantitative polymerase chain reaction (PCR). RESULTS: In this neonatal rat model, RV induced a mild-to-moderate diarrhea in all except one pup of the RV-inoculated rats. RV moderately reduced body weight development from day 6 onwards. On day 7, after 2 d of RV infection, live and dead GG groups gained significantly more weight than the RV group without probiotics [36% (P = 0.001) and 28% (P = 0.031), respectively]. In addition, when compared with the RV control group, both live and dead GG reduced the weight ratio of colon/animal body weight to the same level as in the healthy control group, with reductions of 22% (P = 0.002) and 28% (P GG groups. However, the diarrhea incidence and severity in the GG groups were not statistically significantly different as compared with the RV control group. Moreover, observed diarrhea did not provoke weight loss or death. The RV control group had the largest amount of RV PCR-positive samples among the RV-infected groups, and the live GG group had the smallest amount. Rats receiving live GG had significantly less RV in the colon (P = 0.027) when compared with the RV control group. Live GG was also more effective over dead GG in reducing the quantity of RV from plasma (P = 0.047). CONCLUSION: Both live and dead GG have beneficial effects in RV infection. GG may increase RV

  9. Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in neonatal rats.

    Science.gov (United States)

    Ventola, Hanna; Lehtoranta, Liisa; Madetoja, Mari; Simonen-Tikka, Marja-Leena; Maunula, Leena; Roivainen, Merja; Korpela, Riitta; Holma, Reetta

    2012-11-07

    To study the effects of live and dead Lactobacillus rhamnosus GG (GG) on rotavirus infection in a neonatal rat model. At the age of 2 d, suckling Lewis rat pups were supplemented with either live or dead GG and the treatment was continued daily throughout the experiment. At the age of 5 and 6 d the pups received oral rotavirus (RV) SA-11 strain. The pups were sacrificed at the age of 7 or 8 d by decapitation. The gastrointestinal tract was removed and macroscopic observations were done. The consistency of feces in the colon was classified using a four-tier system. RV was detected from the plasma, small intestine, colon and feces by real-time quantitative polymerase chain reaction (PCR). In this neonatal rat model, RV induced a mild-to-moderate diarrhea in all except one pup of the RV-inoculated rats. RV moderately reduced body weight development from day 6 onwards. On day 7, after 2 d of RV infection, live and dead GG groups gained significantly more weight than the RV group without probiotics [36% (P = 0.001) and 28% (P = 0.031), respectively]. In addition, when compared with the RV control group, both live and dead GG reduced the weight ratio of colon/animal body weight to the same level as in the healthy control group, with reductions of 22% (P = 0.002) and 28% (P GG groups. However, the diarrhea incidence and severity in the GG groups were not statistically significantly different as compared with the RV control group. Moreover, observed diarrhea did not provoke weight loss or death. The RV control group had the largest amount of RV PCR-positive samples among the RV-infected groups, and the live GG group had the smallest amount. Rats receiving live GG had significantly less RV in the colon (P = 0.027) when compared with the RV control group. Live GG was also more effective over dead GG in reducing the quantity of RV from plasma (P = 0.047). Both live and dead GG have beneficial effects in RV infection. GG may increase RV clearance from the body and reduce colon

  10. Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

    Science.gov (United States)

    Pan, Hong-Zhen; Chen, Hwei-Hsien

    2007-03-01

    The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats. These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

  11. Creating rat model for hypoxic brain damage in neonates by oxygen deprivation.

    Science.gov (United States)

    Zhang, Qiaoli; Ding, Yingxue; Yao, Yanqing; Yu, Yang; Yang, Lijun; Cui, Hong

    2013-01-01

    Current study explores the feasibility of using a non-surgical method of oxygen deprivation to create Hypoxic brain damage in neonatal rats for medical studies. 7-day-old Sprague Dowley (SD) rats were kept in a container with low oxygen level (8%) for 1.5h. A second group had bilateral cephalic artery ligation before the 1.5h-low oxygen treatment, a method similar to the popular Rice method, to expose the brain to both hypoxic and ischemic situations. Short term neural functions and brain water weights were evaluated 1 day after the hypoxic treatment. Brain pathology and histology were also examined at 1 day and 3 days after the hypoxic treatment. Both groups showed impaired neural functions and increased brain water weight compared to the controls. Histology studies also revealed injuries in the subcortex, hippocampus and lateral ventricle in the brains from both groups. There is no significant difference in the degree of brain damages observed in the two groups. Our work demonstrated that oxygen deprivation alone is sufficient to cause brain damages similar to those seen in Hypoxic-ischemic brain disease (HIBD). Because this method avoids the invasive surgical procedure and therefore reduces the stress and mortality of laboratory animals during the experiment, we recommend it to be the favorable method for creating rat models for HIBD studies.

  12. Creating rat model for hypoxic brain damage in neonates by oxygen deprivation.

    Directory of Open Access Journals (Sweden)

    Qiaoli Zhang

    Full Text Available Current study explores the feasibility of using a non-surgical method of oxygen deprivation to create Hypoxic brain damage in neonatal rats for medical studies. 7-day-old Sprague Dowley (SD rats were kept in a container with low oxygen level (8% for 1.5h. A second group had bilateral cephalic artery ligation before the 1.5h-low oxygen treatment, a method similar to the popular Rice method, to expose the brain to both hypoxic and ischemic situations. Short term neural functions and brain water weights were evaluated 1 day after the hypoxic treatment. Brain pathology and histology were also examined at 1 day and 3 days after the hypoxic treatment. Both groups showed impaired neural functions and increased brain water weight compared to the controls. Histology studies also revealed injuries in the subcortex, hippocampus and lateral ventricle in the brains from both groups. There is no significant difference in the degree of brain damages observed in the two groups. Our work demonstrated that oxygen deprivation alone is sufficient to cause brain damages similar to those seen in Hypoxic-ischemic brain disease (HIBD. Because this method avoids the invasive surgical procedure and therefore reduces the stress and mortality of laboratory animals during the experiment, we recommend it to be the favorable method for creating rat models for HIBD studies.

  13. Noradrenergic modulation of intrinsic and synaptic properties of lumbar motoneurons in the neonatal rat spinal cord

    Directory of Open Access Journals (Sweden)

    Maylis Tartas

    2010-03-01

    Full Text Available Although it is known that noradrenaline powerfully controls spinal motor networks, few data are available regarding the noradrenergic modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of noradrenergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of noradrenaline and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. Noradrenaline increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1, clonidine (α2 and isoproterenol (β differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1, yohimbine (α2 and propranolol (β. We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by noradrenaline, methoxamine and isoproterenol. On the other hand, noradrenaline, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the noradrenergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord.

  14. Intestinal trefoil factor in treatment of neonatal necrotizing enterocolitis in the rat model.

    Science.gov (United States)

    Shi, Lei; Zhang, Bing-Hong; Yu, Hong-Gang; Yu, Jie-Ping; Xi, Juan-Li

    2007-01-01

    Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. The role of cytokines and growth factors in the pathophysiology of NEC is not yet clearly defined. Among these factors, the intestinal trefoil factor (ITF) is known as cytoprotective to the gut. We studied the cytoprotective effect of trefoil factor in the 1-day-old Wistar rat pup model following hypoxic-ischemic cold stress. In the present study, thirty 1-day-old Wistar rat pups were randomly divided into three groups: Group 1, normal controls: Group 2, NEC; Group 3, NEC+ITF. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4 degrees C for 10 min. The animals were euthanized at development of NEC, and at 96 h the intestinal tissue was processed and examined for histological changes of NEC. The pathological lesions indicated severe separation of the submucosa and lamina propria and tissue necrosis in Group 2, and slight submucosal and lamina propria separation in Group 3. There were no histopathological changes in the controls. The mean of histological grade of group 2 was 2.8 (range 2-4), and 1.2 (range 0-2) in group 3. A difference was found when the two groups were compared (P<0.05). ITF may provide a new way for the therapy of NEC in rats.

  15. Electroacupuncture Ameliorates Cognitive Deficit and Improves Hippocampal Synaptic Plasticity in Adult Rat with Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Lili Guo

    2018-01-01

    Full Text Available Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS. Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA group, and MS with Sham-EA treatment (MS + Sham-EA group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20 and Yintang (GV 29 during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity.

  16. Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome.

    Directory of Open Access Journals (Sweden)

    Stephen W Hartley

    Full Text Available The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.001 on a night/day basis in the pineal gland (70% of these increased at night, 376 genes changed more than 4-fold in either direction. Of these, more than two thousand genes were not previously known to be differentially expressed on a night/day basis. The night/day changes in expression were almost completely eliminated by neonatal removal (SCGX or decentralization (DCN of the superior cervical ganglia (SCG, which innervate the pineal gland. Other than the loss of rhythmic variation, surgical stimulus deprivation had little impact on the abundance of most genes; of particular interest, expression levels of the melatonin-synthesis-related genes Tph1, Gch1, and Asmt displayed little change (less than 35% following DCN or SCGX. However, strong and consistent changes were observed in the expression of a small number of genes including the gene encoding Serpina1, a secreted protease inhibitor that might influence extracellular architecture. Many of the genes that exhibited night/day differential expression in intact animals also exhibited similar changes following in vitro treatment with norepinephrine, a superior cervical ganglia transmitter, or with an analog of cyclic AMP, a norepinephrine second messenger in this tissue. These findings are of significance in that they establish that the pineal-defining transcriptome is established prior to the neonatal period. Further, this work expands our knowledge of the biological process under neural control in this tissue and underlines the value of RNA sequencing in revealing how neurotransmission influences cell

  17. Connectivity of Pacemaker Neurons in the Neonatal Rat Superficial Dorsal Horn

    Science.gov (United States)

    Ford, Neil C.; Arbabi, Shahriar; Baccei, Mark L.

    2014-01-01

    Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS. PMID:25380417

  18. Glutamate antagonism fails to reverse mitochondrial dysfunction in late phase of experimental neonatal asphyxia in rats.

    Science.gov (United States)

    Reddy, Nagannathahalli Ranga; Krishnamurthy, Sairam; Chourasia, Tapan Kumar; Kumar, Ashok; Joy, Keerikkattil Paily

    2011-04-01

    Neonatal asphyxia is a primary contributor to neonatal mortality and neuro-developmental disorders. It progresses in two distinct phases, as initial primary process and latter as the secondary process. A dynamic relationship exists between excitotoxicity and mitochondrial dysfunction during the progression of asphyxic injury. Study of status of glutamate and mitochondrial function in tandem during primary and secondary processes may give new leads to the treatment of asphyxia. Neonatal asphyxia was induced in rat pups on the day of birth by subjecting them to two episodes (10min each) of anoxia, 24h apart by passing 100% N(2) into an enclosed chamber. The NMDA antagonist ketamine (20mg/kg/day) was administered either for 1 day or 7 days after anoxic exposure. Tissue glutamate and nitric oxide were estimated in the cerebral cortex, extra-cortex and cerebellum. The mitochondria from the above brain regions were used for the estimation of malondialdehyde, and activities of superoxide dismutase and succinate dehydrogenase. Mitochondrial membrane potential was evaluated by using Rhodamine dye. Anoxia during the primary process increased glutamate and nitric oxide levels; however the mitochondrial function was unaltered in terms of succinate dehydrogenase and membrane potential. Acute ketamine treatment reversed the increase in both glutamate and nitric oxide levels and partially attenuated mitochondrial function in terms of succinate dehydrogenase activity. The elevated glutamate and nitric oxide levels were maintained during the secondary process but however with concomitant loss of mitochondrial function. Repeated ketamine administration reversed glutamate levels only in the cerebral cortex, where as nitric oxide was decreased in all the brain regions. However, repeated ketamine administration was unable to reverse anoxia-induced mitochondrial dysfunction. The failure of glutamate antagonism in the treatment of asphyxia may be due to persistence of mitochondrial

  19. Neonatal handling and the expression of immunoreactivity to tyrosine hydroxylase in the hypothalamus of adult male rats

    Directory of Open Access Journals (Sweden)

    E.E.S. Hermel

    2001-09-01

    Full Text Available Neonatal handling has long-lasting effects on behavior and stress reactivity. The purpose of the present study was to investigate the effect of neonatal handling on the number of dopaminergic neurons in the hypothalamic nuclei of adult male rats as part of a series of studies that could explain the long-lasting effects of neonatal stimulation. Two groups of Wistar rats were studied: nonhandled (pups were left undisturbed, control and handled (pups were handled for 1 min once a day during the first 10 days of life. At 75-80 days, the males were anesthetized and the brains were processed for immunohistochemistry. An anti-tyrosine hydroxylase antibody and the avidin-biotin-peroxidase method were used. Tyrosine hydroxylase-immunoreactive (TH-IR neurons were counted bilaterally in the arcuate, paraventricular and periventricular nuclei of the hypothalamus in 30-µm sections at 120-µm intervals. Neonatal handling did not change the number of TH-IR neurons in the arcuate (1021 ± 206, N = 6; 1020 ± 150, N = 6; nonhandled and handled, respectively, paraventricular (584 ± 85, N = 8; 682 ± 62, N = 9 or periventricular (743 ± 118, N = 7; 990 ± 158, N = 7 nuclei of the hypothalamus. The absence of an effect on the number of dopaminergic cells in the hypothalamus indicates that the reduction in the amount of neurons induced by neonatal handling, as shown by other studies, is not a general phenomenon in the brain.

  20. Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

    Science.gov (United States)

    Winston, John H; Sarna, Sushil K

    2016-07-01

    Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. Copyright © 2016 the American Physiological Society.

  1. Projection patterns of commissural interneurons in the lumbar spinal cord of the neonatal rat

    DEFF Research Database (Denmark)

    Stokke, Mathis Frøshaug; Nissen, Ulla Vig; Glover, Joel C.

    2002-01-01

    We have studied the axonal projection patterns of commissural interneurons (CINs) in the neonatal rat spinal cord. Some CINs are integral components of the neuronal networks in the vertebrate spinal cord that generate locomotor activity. By using differential retrograde labeling protocols...... with fluorescent dextran amines, we show that CINs with ascending axons (ascending CINs, or aCINs) and CINs with descending axons (descending CINs, or dCINs) constitute largely different populations. We show that aCINs and dCINs occupy partially overlapping domains in the transverse plane. The aCINs are located...... and a half segment rostrally or caudally and are present in roughly equal numbers. We also demonstrate the presence of a third, smaller population of CINs whose axons bifurcate to project for at least one and a half segment both rostrally and caudally (adCINs). The adCINs are located predominantly among...

  2. The serotonin reuptake inhibitor citalopram suppresses activity in the neonatal rat barrel cortex in vivo.

    Science.gov (United States)

    Akhmetshina, Dinara; Zakharov, Andrei; Vinokurova, Daria; Nasretdinov, Azat; Valeeva, Guzel; Khazipov, Roustem

    2016-06-01

    Inhibition of serotonin uptake, which causes an increase in extracellular serotonin levels, disrupts the development of thalamocortical barrel maps in neonatal rodents. Previous in vitro studies have suggested that the disruptive effect of excessive serotonin on barrel map formation involves a depression at thalamocortical synapses. However, the effects of serotonin uptake inhibitors on the early thalamocortical activity patterns in the developing barrel cortex in vivo remain largely unknown. Here, using extracellular recordings of the local field potentials and multiple unit activity (MUA) we explored the effects of the selective serotonin reuptake inhibitor (SSRI) citalopram (10-20mg/kg, intraperitoneally) on sensory evoked activity in the barrel cortex of neonatal (postnatal days P2-5) rats in vivo. We show that administration of citalopram suppresses the amplitude and prolongs the delay of the sensory evoked potentials, reduces the power and frequency of the early gamma oscillations, and suppresses sensory evoked and spontaneous neuronal firing. In the adolescent P21-29 animals, citalopram affected neither sensory evoked nor spontaneous activity in barrel cortex. We suggest that suppression of the early thalamocortical activity patterns contributes to the disruption of the barrel map development caused by SSRIs and other conditions elevating extracellular serotonin levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

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    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  4. SOMATIC VERSUS DENDRITIC RESPONSES TO HYPERCAPNIA IN CHEMOSENSITIVE LOCUS COERULEUS NEURONS FROM NEONATAL RATS

    Science.gov (United States)

    Ritucci, Nick A.; Dean, Jay B.; Putnam, Robert W.

    2005-01-01

    Cardiorespiratory control is mediated in part by central chemosensitive neurons that respond to increased CO2 (hypercapnia). Activation of these neurons is believed to involve hypercapnia-induced decreases in intracellular pH (pHi). All previous measurements of hypercapnia-induced pHi changes in chemosensitive neurons have been made from the soma, but chemosensitive signaling could be initiated in the dendrites of these neurons. In this study, membrane potential (Vm) and pHi were measured simultaneously in chemosensitive locus coeruleus (LC) neurons from neonatal rat brainstem slices using whole-cell pipettes and the pH-sensitive fluorescent dye pyranine. We measured pHi from the soma as well as from primary dendrites to a distance of 160 μm from the edge of the soma. Hypercapnia (15% CO2, pHo 7.00; control: 5% CO2, pHo 7.45) resulted in an acidification of similar magnitude in dendrites and soma (about 0.26 pH unit), but that was faster in the more distal regions of the dendrites. Neither the dendrites nor the soma exhibited pHi recovery during hypercapnia-induced acidification, but both regions contain pH-regulating transporters since they exhibit pHi recovery from an NH4Cl prepulse-induced acidification (at constant pHo 7.45). Exposing a portion of the dendrites to hypercapnic solution did not increase firing rate, but exposing the soma to hypercapnic solution resulted in a near maximal increase in firing rate. These data show that while the pHi response to hypercapnia is similar in the dendrites and soma, somatic exposure to hypercapnia plays a major role in the activation of chemosensitive LC neurons from neonatal rats. PMID:16014703

  5. Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis.

    Science.gov (United States)

    Jilling, Tamas; Lu, Jing; Jackson, Michele; Caplan, Michael S

    2004-04-01

    The histopathology of necrotizing enterocolitis (NEC) is characterized by destruction of the mucosal layer in initial stages and by transmural necrosis of the intestinal wall in advanced stages of the disease. To test the hypothesis that enhanced epithelial apoptosis is an initial event underlying the gross histologic changes, we analyzed epithelial apoptosis and tissue morphology in an animal model of NEC and evaluated the effect of caspase inhibition on the incidence of experimental NEC in this model. Apoptosis was analyzed with terminal deoxynucleotidyltransferase-mediated dUTP-FITC nick end labeling (TUNEL) staining in intestinal sections and by measuring caspase 3 activity from intestinal lysates of neonatal rats subjected to formula feeding and cold/asphyxia stress (FFCAS) and from mother-fed (MF) controls. Morphologic evaluation was based on hematoxylin and eosin staining of intestinal sections. FFCAS resulted in histologic changes consistent with NEC, which were absent from MF animals. FFCAS was also associated with a significantly increased rate of nuclear DNA fragmentation in the small intestinal epithelium compared with MF. Elevated tissue caspase 3 activity confirmed the presence of apoptosis in samples with increased DNA fragmentation. Analysis of the coincidence of morphologic damage and apoptosis in corresponding tissue sections indicated that apoptosis precedes gross morphologic changes in this model. Furthermore, supplementation of formula with 8 boc-aspartyl(OMe)-fluoromethylketone, a pan-caspase inhibitor, significantly reduced the incidences of apoptosis and experimental NEC. These findings indicate that in neonatal rats FFCAS induces epithelial apoptosis that serves as an underlying cause for subsequent gross tissue necrosis.

  6. Feeding of Nigella sativa during neonatal and juvenile growth improves learning and memory of rats

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    Farimah Beheshti

    2016-04-01

    Full Text Available The positive roles of antioxidants on brain development and learning and memory have been suggested. Nigella sativa (NS has been suggested to have antioxidant and neuroprotective effects. This study was done to investigate the effects of feeding by the hydro-alcoholic extract of NS during neonatal and juvenile growth on learning and memory of rats. The pregnant rats were kept in separate cages. After delivery, they were randomly divided into four Groups including: (1 control; (2 NS 100 mg/kg (NS 100; (3 NS 200 mg/kg (NS 200; and (4 NS 400 mg/kg (NS 400. Rats in the control group (Group 1 received normal drinking water, whereas Groups 2, 3, and 4 received the same drinking water supplemented with the hydro-alcoholic extract of NS (100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively from the 1st day after birth through the first 8 weeks of life. After 8 weeks, 10 male offspring from each group were randomly selected and tested in the Morris water maze (MWM and passive avoidance (PA test. Finally, the brains were removed and total thiol groups and malondialdehyde (MDA concentrations were determined. In the MWM, treatment by 400 mg/kg extract reduced both the time latency and the distance traveled to reach the platform compared to the control group (p < 0.05–p < 0.01. Both 200 mg/kg and 400 mg/kg of the extract increased the time spent in the target quadrant (p < 0.05–p < 0.01. In the PA test, the treatment of the animals by 200 mg/kg and 400 mg/kg of NS extract significantly increased the time latency for entering the dark compartment (p < 0.05–p < 0.001. Pretreatment of the animals with 400 mg/kg of NS extract decreased the MDA concentration in hippocampal tissues whereas it increased the thiol content compared to the control group (p < 0.001. These results allow us to propose that feeding of the rats by the hydro-alcoholic extract of NS during neonatal and juvenile growth has positive effects on learning and memory

  7. Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

    Science.gov (United States)

    Peterson, Bethany L; Park, Thomas J; Larson, John

    2012-01-11

    Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Distracción ósea: tratamiento de la apnea obstructiva en neonatos con micrognatia Mandibular distraction: treatment of obstructive apnea in neonates with micrognathia

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    Adoración Martínez Plaza

    2011-06-01

    Full Text Available Las malformaciones craneofaciales (secuencia de Pierre Robin, síndrome de Threacher-Collins, síndrome de Nager, etc. con frecuencia van asociadas a hipoplasia mandibular grave, que puede causar obstrucción de la vía aérea superior por retroposición de la base de la lengua dentro del espacio faríngeo posterior. La mayoría de los pacientes responden al tratamiento postural, en decúbito prono, puede ser necesario controlar la saturación de oxígeno, insertar un tubo nasofaríngeo e incluso intratraqueal. En casos más graves con pausas prolongadas y frecuentes de apnea, la traqueostomía puede ser necesaria, pero se asocia a una alta morbilidad y, ocasionalmente, mortalidad. En los últimos 2 años, en la Unidad Multidisciplinaria de Labio y Fisura Palatina del Hospital Virgen de las Nieves de Granada, se ha tratado a 4 niños con apnea obstructiva grave secundaria a hipoplasia mandibular grave mediante distracción mandibular osteogénica, y este procedimiento se ha mostrado eficaz en la resolución del problema. Ha evitado la traqueostomía y se ha elongado la mandíbula en el plazo de 3-4 semanas. En este tiempo han desaparecido los problemas respiratorios obstructivos, así como también de la deglución, y los resultados estéticos obtenidos han resultado excelentes y las complicaciones, por el momento, mínimas.Craniofacial malformations (Pierre-Robin sequence, Treacher-Collins syndrome, Nager syndrome, etc. are frequently accompanied by severe mandibular hypoplasia, which can cause upper airway obstruction due to retroposition of the base of the tongue in the posterior pharyngeal space. The majority of patients respond to postural treatment in decubitus prono. It may be necessary to monitor oxygen saturation and insert a nasopharyngeal or even an endotracheal tube. Tracheostomy may be necessary in more serious cases with long and frequent apnea pauses, but it is associated with high morbidity and occasional mortality. In the last

  9. Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats

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    Ning Wang

    2018-03-01

    Full Text Available Background/Aims: Isoflurane inhibited neurogenesis and induced subsequent neurocognitive deficits in developing brain. Simvastatin exerts neuroprotection in a wide range of brain injury models. In the present study, we investigated whether simvastatin could attenuate neurogenetic inhibition and cognitive deficits induced by isoflurane exposure in neonatal rats. Methods: Sprague-Dawley rats at postnatal day (PND 7 and neural stem cells (NSCs were treated with either gas mixture, isoflurane, or simvastatin 60 min prior to isoflurane exposure, respectively. The rats were decapitated at PND 8 and PND 10 for detection of neurogenesis in the subventricular zone (SVZ and subgranular zone (SGZ of the hippocampus by immunostaining. NSC proliferation, viability and apoptosis were assessed by immunohistochemistry, CCK-8 and TUNEL, respectively. The protein expressions of caspase-3, p-Akt and p-GSK-3β both in vivo and vitro were assessed by western blotting. Cognitive functions were assessed by Morris Water Maze test and context fear conditioning test at the adult. Results: Isoflurane exposure inhibited neurogenesis in the SVZ and SGZ, decreased NSC proliferation and viability, promoted NSC apoptosis and led to late cognitive deficits. Furthermore, isoflurane increased caspase-3 expression and decreased protein expressions of p-Akt and p-GSK-3β both in vivo and in vitro. Pretreatment with simvastatin attenuated isoflurane-elicited changes in NSCs and cognitive function. Co-treatment with LY294002 reversed the effect of simvastatin on NSCs in vitro. Conclusion: We for the first time showed that simvastatin, by upregulating Akt/GSK-3β signaling pathway, alleviated isoflurane-induced neurogenetic damage and neurocognitive deficits in developing rat brain.

  10. Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

    Science.gov (United States)

    Alquicer, Glenda; Silva-Gómez, Adriana B; Peralta, Fernando; Flores, Gonzalo

    2004-04-01

    The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

  11. [Effect of Xinmailong on hypoxia-inducible factor-1alpha expression in neonatal rats with asphyxia].

    Science.gov (United States)

    Huang, Li-Xin; Wu, Xing-Heng

    2009-08-01

    Xinmailong, a compound extracted from Periplaneta americana, is used for the treatment of cardiovascular diseases. This study investigated the effects of Xinmailong on myocardial hypoxia-inducible factor-1alpha (HIF-1alpha) and plasma endothelin-1(ET-1) levels in neonatal rats with asphyxia and explored the protection mechanism of Xinmailong in hypoxia-ischemic myocardial injury. Seven-day-old Sprague-Dawley rats were randomly divided into three groups (n=30 each): sham-operated, asphyxia, Xinmailong-treated asphyxia. Each group was randomly subdivided into three groups according to the observed time points: 6 hrs, 24 hrs and 72 hrs. Xinmailong (5 mg/kg) was intraperitoneally injected to the rats in the Xinmailong-treated group five minutes before asphyxia. Myocardial HIF-1alpha expression, and plasma ET-1 and creatine kinase (CK) levels were measured. The histopathologic changes of the myocardium were observed by hematoxylin-eosin staining. Four rats died in the asphyxia group while only one died in the Xinmailong-treated group during the experiment. The plasma ET-1 and CK levels as well as myocardial HIF-1alpha expression increased at 6 hrs, reached a peak at 24 hrs, and declined at 72 hrs after asphyxia in the asphyxia group, being higher than that in the sham-operated group (Pasphyxia in the asphyxia group. Myocardial HIF-1alpha expression was positively correlated with plasma ET-1 levels (r=0.876, Pasphyxia group (PAsphyxia leads to increase in myocardial HIF-1alpha expression and plasma levels of ET-1 and CK. Xinmailong can reduce the myocardial expression of HIF-1alpha and decrease plasma ET-1 levels, thus alleviating hypoxia-ischemic myocardial injury.

  12. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

    Science.gov (United States)

    Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

    2016-08-10

    Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes

  13. Th e eff ects of Nigella Sativa extract on renal tissue oxidative damage during neonatal and juvenile growth in propylthiouracil-induced hypothyroid rats

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    Mohebbati R.

    2017-04-01

    Full Text Available Objective. We investigated the effects of hydroalcoholic extract of Nigella sativa (NS on renal tissue oxidative damage associated with propylthiouracil (PTU-induced hypothyroidism during neonatal and juvenile growth in rats.

  14. Effect of reduced articular function on deposition of type I and type II collagens in the mandibular condylar cartilage of the rat.

    Science.gov (United States)

    Pirttiniemi, P; Kantomaa, T; Salo, L; Tuominen, M

    1996-01-01

    A group of rats was fed a soft diet after weaning and the incisors shortened regularly to keep them out of occlusion. The controls were fed a hard diet. Immunohistochemical techniques and image analysis were employed to investigate deposition of pro-type I collagen and type II collagen, and the thickness of articular cartilage layers in the mandibular condyle. The immunostaining against pro-type I collagen was most intense intracellularly in the fibrous and upper chondroblast layers in 30- and 50-day-old rats fed a hard diet. In the rats fed a soft diet, marked intra- and extracellular staining against pro-type I collagen was visible in the upper chondroblast and upper hypertrophic layers but also in the lower hypertrophic layer. The intensity of staining against type II collagen was weak in animals on a soft diet, while in the animals fed a hard diet the staining was intense in the superior layers of mature chondroblasts. The total number of chondroblasts recorded was reduced by 35 percent at the age of 50 days in the soft-diet compared to the hard-diet animals. The results show that the deposition of type I and II collagens, the thickness of the cartilage cell layers and the number of chondrocytes are sensitive to alterations in loading.

  15. Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats

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    Chong Chen

    2015-04-01

    Full Text Available Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8% sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4–6 were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

  16. Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects

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    Bhutta Adnan T

    2008-08-01

    Full Text Available Abstract Background Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. Methods Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9, Ketamine (K, 2.5 mg/kg × 2, N = 9, Ketamine prior to formalin (KF, N = 9, or undisturbed controls (C, N = 9. Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15 were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB, followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27 in the neonatal period. Results Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult

  17. The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Spinetta, Michael J; Thomas, Jennifer D; Riley, Edward P

    2011-01-01

    The third trimester in human fetal development represents a critical time of brain maturation referred to as the "brain growth spurt". This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats. On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning. Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure. These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats.

    Science.gov (United States)

    Abdollahi, M; Zuki, A B Z; Goh, Y M; Rezaeizadeh, A; Noordin, M M

    2011-01-01

    The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (Pdiabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic β-cells in the nSTZ rats.

  19. Sex Differences in Behavioral Outcomes Following Temperature Modulation During Induced Neonatal Hypoxic Ischemic Injury in Rats

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    Amanda L. Smith

    2015-05-01

    Full Text Available Neonatal hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain can cause various degrees of tissue damage, as well as subsequent cognitive/behavioral deficits such as motor, learning/memory, and auditory impairments. These outcomes frequently result from cardiovascular and/or respiratory events observed in premature infants. Data suggests that there is a sex difference in HI outcome, with males being more adversely affected relative to comparably injured females. Brain/body temperature may play a role in modulating the severity of an HI insult, with hypothermia during an insult yielding more favorable anatomical and behavioral outcomes. The current study utilized a postnatal day (P 7 rodent model of HI injury to assess the effect of temperature modulation during injury in each sex. We hypothesized that female P7 rats would benefit more from lowered body temperatures as compared to male P7 rats. We assessed all subjects on rota-rod, auditory discrimination, and spatial/non-spatial maze tasks. Our results revealed a significant benefit of temperature reduction in HI females as measured by most of the employed behavioral tasks. However, HI males benefitted from temperature reduction as measured on auditory and non-spatial tasks. Our data suggest that temperature reduction protects both sexes from the deleterious effects of HI injury, but task and sex specific patterns of relative efficacy are seen.

  20. All-trans-retinoic acid attenuates intestinal injury in a neonatal rat model of necrotizing enterocolitis.

    Science.gov (United States)

    Ozdemir, Ramazan; Yurttutan, Sadık; Sari, Fatma Nur; Oncel, Mehmet Yekta; Erdeve, Omer; Unverdi, Hatice Germen; Uysal, Bülent; Dilmen, Ugur

    2013-01-01

    Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4°C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-α levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p intestinal injury through its anti-inflammatory and antioxidant properties. Copyright © 2013 S. Karger AG, Basel.

  1. Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

    Science.gov (United States)

    Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

    2017-07-01

    In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (pmaternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in

  2. Developmental programming of eNOS uncoupling and enhanced vascular oxidative stress in adult rats after transient neonatal oxygen exposure.

    Science.gov (United States)

    Yzydorczyk, Catherine; Comte, Blandine; Huyard, Fanny; Cloutier, Anik; Germain, Nathalie; Bertagnolli, Mariane; Nuyt, Anne Monique

    2013-01-01

    The authors have previously shown that neonatal hyperoxic stress leads to high blood pressure, impaired endothelium-mediated vasodilatation, and increased vascular production of superoxide anion by NAD(P)H oxidase in adulthood. However, it is unknown whether changes in nitric oxide (NO) production and/or bioinactivation prevail and whether NO synthase (NOS) is also a source of superoxide. The purpose of this study was to evaluate whether adult animals exposed to neonatal hyperoxic stress have impaired vascular NO production associated with NOS uncoupling participating to vascular superoxide production and vascular dysfunction. In adult male rats exposed to 80% oxygen from day 3 to 10 of life (H, n = 6) versus room air controls (CTRL, n = 6), vascular (aorta) NO production is decreased at baseline (CTRL: 21 ± 1 vs. H: 16 ± 2 4,5-diaminofluorescein diacetate fluorescence intensity arbitrary units; P blood pressure after a brief neonatal oxygen exposure.

  3. [The protective effect of propofol pretreatment on glutamate injury of neonatal rat brain slices].

    Science.gov (United States)

    Zhou, Xiao-feng; Huang, Ding-ding; Wang, Di-fen; Fu, Jiang-quan

    2012-12-01

    To study the protective effect of propofol precondition against glutamate (Glu) neurotoxicity to neonatal rat cerebrocortical slices. Brain slices of Sprague-Dawley (SD) rats were cultured in vitro and observed the morphologic changes. Brain slices were randomly divided into three groups: blank control group, Glu injury group (1 mmol/L Glu for 0.5 hour), propofol precondition group (20 mg/L propofol for 24 hours), each n=12. Changes in pathological and ultra-structure of cells were observed using microscope. Lactate dehydrogenase (LDH) leakage rate was measured. Meanwhile, the expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemical technology, then the positive cell were counted. Cultured brain slices of cell were intact and survived well. Hematoxylin-eosin (HE) staining, electron microscopy and LDH test results showed that cerebral film neuron severely damage, gliosis, edema, LDH leakage rate in Glu injury group were significantly more severe compared with blank control group [(68.5±2.0)% vs. (16.0±2.5)%, P<0.01]. Reduce the brain slice of the propofol pretreatment group of neuronal cell jury, cell shape recovery significantly reduced LDH leakage rate compared with the Glu injury group [(38.5±2.4)% vs. (68.5±2.0)%, P<0.05]. Immunohistochemical detection of GFAP expression of Glu injury group glial cell body swelling, producing increase in the number of GFAP positive reaction strong, the number of positive cells compared with blank control group was significantly increased (50±5 cells/HP vs. 10±3 cells/HP, P<0.01). The recovery of propofol pretreatment group glial cell morphology, cell processes slender GFAP positive reaction decreased the number of positive cells compared with the Glu injury group was significantly decreased (30±4 cells/HP vs. 50±5 cells/HP, P<0.05). Propofol pretreatment has protective effect against Glu injured rat cerebrocortical slices.

  4. Non-classical effects of androgens on testes from neonatal rats.

    Science.gov (United States)

    da Rosa, Luciana Abreu; Escott, Gustavo Monteiro; Cavalari, Fernanda Carvalho; Schneider, Clara Maria Müller; de Fraga, Luciano Stürmer; Loss, Eloísa da Silveira

    2015-01-01

    The intratesticular testosterone concentration is high during the early postnatal period although the intracellular androgen receptor expression (iAR) is still absent in Sertoli cells (SCs). This study aimed to evaluate the non-classical effects of testosterone and epitestosterone on calcium uptake and the electrophysiological effects of testosterone (1μM) on SCs from rats on postnatal day (pnd) 3 and 4 with lack of expression of the iAR. In addition, crosstalk on the electrophysiological effects of testosterone and epitestosterone with follicle stimulating hormone (FSH) in SCs from 15-day-old rats was evaluated. The isotope (45)Ca(2+) was utilized to evaluate the effects of testosterone and epitestosterone in calcium uptake. The membrane potential of SCs was recorded using a standard single microelectrode technique. No immunoreaction concerning the iAR was observed in SCs on pnd 3 and 4. At this age, both testosterone and epitestosterone increased the (45)Ca(2+) uptake. Testosterone promoted membrane potential depolarization of SCs on pnd 4. FSH application followed by testosterone and epitestosterone reduced the depolarization of the two hormones. Application of epitestosterone 5 min after FSH resulted in a delay of epitestosterone-promoted depolarization. The cell resistance was also reduced. Thus, in SCs from neonatal Wistar rats, both testosterone and epitestosterone act through a non-classical mechanism stimulating calcium uptake in whole testes, and testosterone produces a depolarizing effect on SC membranes. Testosterone and epitestosterone stimulates non-classical actions via a membrane mechanism, which is independent of iAR. FSH and testosterone/epitestosterone affect each other's electrophysiological responses suggesting crosstalk between the intracellular signaling pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Neonatal stress tempers vulnerability of acute stress response in adult socially isolated rats

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    Mariangela Serra

    2014-06-01

    Full Text Available Adverse experiences occurred in early life and especially during childhood and adolescence can have negative impact on behavior later in life and the quality of maternal care is considered a critical moment that can considerably influence the development and the stress responsiveness in offspring. This review will assess how the association between neonatal and adolescence stressful experiences such as maternal separation and social isolation, at weaning, may influence the stress responsiveness and brain plasticity in adult rats. Three hours of separation from the pups (3-14 postnatal days significantly increased frequencies of maternal arched-back nursing and licking-grooming by dams across the first 14 days postpartum and induced a long-lasting increase in their blood levels of corticosterone. Maternal separation, which per sedid not modified brain and plasma allopregnanolone and corticosterone levels in adult rats, significantly reduced social isolation-induced decrease of the levels of these hormones. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were exposed to maternal separation was markedly reduced respect to that observed in socially isolated animals. Our results suggest that in rats a daily brief separation from the mother during the first weeks of life, which per se did not substantially alter adult function and reactivity of hypothalamic-pituitary-adrenal (HPA axis, elicited a significant protection versus the subsequent long-term stressful experience such that induced by social isolation from weaning. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in NeonatologyGuest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  6. Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

    Directory of Open Access Journals (Sweden)

    Ribeiro Carla

    2012-02-01

    Full Text Available Abstract Background This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. Methods Wistar rats were used and divided into six groups: sedentary alloxan (SA, sedentary control (SC, continuous trained alloxan (CA, intermittent trained alloxan (IA, continuous trained control (CC and intermittent trained control (IC. Alloxan (250 mg/kg body weight was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. Results At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. Conclusion It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.

  7. Estudio experimental sobre la regeneración ósea mandibular de la rata con diferentes biomateriales Experimental study in rats of mandibular bone regeneration with different biomaterials

    Directory of Open Access Journals (Sweden)

    B. Peral Cagigal

    2008-10-01

    Full Text Available Objetivo. Los defectos óseos mandibulares resultantes de infecciones, traumatismos o resecciones oncológicas, van a producir severos problemas funcionales y/o estéticos, que van a precisar de un tratamiento complejo. Durante los últimos años, las aportaciones al terreno de la reconstrucción ósea se han debatido entre métodos tan dispares como la distracción ósea o la utilización de colgajos libres microvascularizados, pasando por un sin fin de biomateriales. El objetivo de este estudio fue comparar la formación de hueso nuevo tras la aplicación de una membrana reabsorbible y dos tipos de sustitutivos óseos. Material y método. Se utilizaron 24 ratas adultas macho tipo Wistar, en las que se crearon defectos circulares de 4 mm de diámetro en ambos lados de la mandíbula. Se formaron 4 grupos, un grupo control y 3 grupos experimentales. Los animales fueron sacrificados a las 3 y 6 semanas de la cirugía, realizándose un análisis radiológico e histológico. Resultados. Los defectos control no mostraron formación ósea, apareciendo una reparación por tejido fibroso. La membrana de hueso utilizada de forma aislada, actuó como una barrera eficaz excluyendo los tejidos no osteogénicos, pero no se produjo reparación total del defecto en ningún caso. El grupo de Colloss® y membrana, mostró una regeneración ósea completa del defecto a las 6 semanas. El grupo de NovaBone® y membrana, no mostró formación ósea, apareciendo las partículas del biomaterial ocupando el defecto. Conclusiones. La regeneración ósea fue significativamente mayor en los defectos rellenos con Colloss® y cubiertos con la membrana de Lambone®, comparado con los otros grupos experimentales.Objective. Mandibular bone defects can occur as a result of trauma, neoplasm, or infectious conditions. Such conditions often are associated with severe funtional and esthetic problems. Corrective treatment often is complicated by limitations in tissue adaptation. The

  8. Hypothyroidism during neonatal and perinatal period induced by thyroidectomy of the mother causes depressive-like behavior in prepubertal rats

    OpenAIRE

    Ortiz-Butron, Rocio

    2010-01-01

    Marisol Pineda-Reynoso, Edgar Cano-Europa, Vanessa Blas-Valdivia, Adelaida Hernandez-Garcia, Margarita Franco-Colin, Rocio Ortiz-ButronDepartamento de Fisiología ‘Mauricio Russek Berman,’ Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, MéxicoAbstract: The objective of this study was to see if neonatal and perinatal hypothyroidism caused anxiety and depressive-like behaviors. Twenty female Wistar rats were randomly divi...

  9. Neonatal injury rapidly alters markers of pain and stress in rat pups.

    Science.gov (United States)

    Victoria, Nicole C; Karom, Mary C; Eichenbaum, Hila; Murphy, Anne Z

    2014-01-01

    Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long-term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety- and stress-provoking stimuli. These long-term changes in pain and stress responsiveness are accompanied by two-fold increases in central met-enkephalin and β-endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met-enkephalin and β-endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met-enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β-endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post-injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury-induced changes become programmed and permanent. Copyright © 2013 Wiley Periodicals, Inc.

  10. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats.

    Science.gov (United States)

    Ahn, Hyo-Jin; An, Beum-Soo; Jung, Eui-Man; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-09-01

    Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. Copyright © 2012 Wiley Periodicals, Inc.

  11. Effects of maternal high fat intake during pregnancy and lactation on total cholesterol and adipose tissue in neonatal rats

    Directory of Open Access Journals (Sweden)

    M. S. Lima

    2018-01-01

    Full Text Available Abstract Aim Obesity during pregnancy is one of the most established risk factors for negative long-term programming. The aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during pregnancy and lactation on the weight gain, visceral adipose tissue and cholesterolemia in neonatal rats. Methods Wistar rats were divided into two groups according to the mother's diet during pregnancy and lactation: Control group (CG, n = 12 were the offspring of rats fed a standard diet (4% lipid and the Test group (TG, n = 12 were pups rats fed on a high fat diet (23% lipid. The weight of the animals was measured on alternate days until the 22nd day of life, when collected visceral adipose tissue and blood were collected for biochemical analysis. For statistical analysis the Student t test, Sidak´s teste and two way ANOVA was used, with p <0.05. Results the test group showed differences in weight gain, visceral adipose tissue and higher cholesterol. Conclusion a maternal exposure to a high-fat diet during pregnancy and lactation can promote changes in weight gain, hypercholesterolemia and an increase in adipose tissue in neonatal rats.

  12. CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.

    Science.gov (United States)

    Cetinkaya, Merih; Cansev, Mehmet; Cekmez, Ferhat; Tayman, Cuneyt; Canpolat, Fuat Emre; Kafa, Ilker M; Uysal, Sema; Tunc, Turan; Sarici, S Umit

    2013-07-01

    Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC

  13. Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach.

    Science.gov (United States)

    Danilović Luković, Jelena; Korać, Aleksandra; Milošević, Ivan; Lužajić, Tijana; Puškaš, Nela; Kovačević Filipović, Milica; Radovanović, Anita

    2016-11-01

    Thyroid hormones (TH) are one of the key factors for normal prenatal development in mammals. Previously, we showed that subclinical maternal hypothyroidism leads to premature atresia of ovarian follicles in female rat offspring in the pre-pubertal and pubertal periods. The influence of decreased concentration of TH on primordial follicles pool formation during neonatal and early infantile period of rat pups was not investigated previously. Maternal hypothyroidism during pregnancy has irreversible negative influence on primordial follicles pool formation and population of resting oocytes in female rat offspring. The study was done on neonatal and early infantile control (n-10) and hypothyroid (n-10) female rat pups derived from control (n-6) and propylthiouracil (PTU) treated pregnant dams (n-6), respectively. Ovaries of all pups were removed and processed for light and transmission electron microscopy (TEM). Number of nests, oogonia and oocytes per nest, primordial, primary, secondary and preantral follicles were determined. Screening for overall calcium presence in ovarian tissue was done using Alizarin red staining. Morphology and volume density of nucleus, mitochondria and smooth endoplasmic reticulum (sER) in the oocytes in primordial follicles was also assessed. Caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), both markers for apoptosis, and proliferating cell nuclear antigen (PCNA) for proliferation were determined in oocytes and granulosa cells in different type of follicles. In neonatal period, ovaries of hypothyroid pups had a decreased number of oogonia, oocytes and nests, an increased number of primordial follicles and a decreased number of primary and secondary follicles, while in early infantile period, increased number of primary, secondary and preantral follicles were found. Alizarin red staining was intense in hypothyroid neonatal rats that also had the highest content of dilated sER. Number of mitochondria with

  14. Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

    Science.gov (United States)

    Watanabe, Kazushi; Hamada, Fumiaki; Wakatsuki, Akihiko; Nagai, Ryuhei; Shinohara, Koichi; Hayashi, Yoshihiro; Imamura, Rina; Fukaya, Takao

    2012-08-01

    The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.

  15. Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats.

    Science.gov (United States)

    Galindo, Lígia Cristina Monteiro; Barros, Manuella da Luz Duarte; Pinheiro, Isabeli Lins; Santana, Ricardo Vinicius de Carvalho; de Matos, Rhowena Jane Barbosa; Leandro, Carol Góis; de Souza, Sandra Lopes; de Castro, Raul Manhães

    2015-11-01

    Serotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood. Investigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C). In each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to the 21(st) postnatal day, C pups received sterile saline while F pups received fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC). The use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC. These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. [Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

    Science.gov (United States)

    Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

    2008-11-04

    To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

  17. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

    Science.gov (United States)

    Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

    2016-02-01

    Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

    Science.gov (United States)

    Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

    2018-02-06

    Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Hypothyroidism during neonatal and perinatal period induced by thyroidectomy of the mother causes depressive-like behavior in prepubertal rats

    Directory of Open Access Journals (Sweden)

    Marisol Pineda-Reynoso

    2010-04-01

    Full Text Available Marisol Pineda-Reynoso, Edgar Cano-Europa, Vanessa Blas-Valdivia, Adelaida Hernandez-Garcia, Margarita Franco-Colin, Rocio Ortiz-ButronDepartamento de Fisiología ‘Mauricio Russek Berman,’ Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, MéxicoAbstract: The objective of this study was to see if neonatal and perinatal hypothyroidism caused anxiety and depressive-like behaviors. Twenty female Wistar rats were randomly divided into two groups: 1 thyroidectomy caused hypothyroidism, in which the thyroid gland had been removed and the parathyroid reimplanted; and 2 false thyroidectomy. The thyroidectomy was made on rats anesthetized with ketamine-xylazine. The rats were mated and one day after giving birth, eight pups were assigned to each group randomly and they were distributed into two groups: a hypothyroid group containing male pups of a hypothyroid mother with a hypothyroid wet nurse; and a euthyroid group of male pups of a euthyroid mother with a euthyroid wet nurse. We analyzed the behavioral test at a prepubertal age. The neonatal and perinatal hypothyroidism caused by the mother’s thyroidectomy caused a decrease in body weight and length. We found that the neonatal and perinatal hypothyroidism enhanced the total exploratory activity without affecting social contact and the time spent in the open and closed arms in an elevated plus-maze. The hypothyroidism caused immobility without altering the lower climbing duration in the swimming test. This study shows a novel model to cause neonatal and perinatal hypothyroidism without using pharmacological drugs. We demonstrated that hypothyroid animals had a reduction in body weight and length, a retardation of neurodevelopment, and they had depressive-like behavior.Keywords: perinatal hypothyroidism, thyroidectomy, thyroid hormone, behavior, metabolism

  20. Epigenetic Manipulation of Brain-derived Neurotrophic Factor Improves Memory Deficiency Induced by Neonatal Anesthesia in Rats.

    Science.gov (United States)

    Wu, Jiang; Bie, Bihua; Naguib, Mohamed

    2016-03-01

    Although neonatal exposure to anesthetic drugs is associated with memory deficiency in rodent models and possibly in pediatric patients, the underlying mechanisms remain elusive. The authors tested their hypothesis that exposure of the developing brain to anesthesia triggers epigenetic modification, involving the enhanced interaction among transcription factors (histone deacetylase 2, methyl-cytosine-phosphate-guanine-binding protein 2, and DNA methyltransferase 1) in Bdnf promoter region(s) that inhibit brain-derived neurotrophic factor (BDNF) expression, resulting in insufficient drive for local translation of synaptic mRNAs. The authors further hypothesized that noninvasive environmental enrichment (EE) will attenuate anesthesia-induced epigenetic inhibition of BDNF signaling and memory loss in rodent models. Seven days after birth (P7), neonatal rats were randomly assigned to receive either isoflurane anesthesia for 6 h or sham anesthesia. On P21, pups were weaned, and animals were randomly assigned to EE or a standard cage environment (no EE). Behavioral, molecular, and electrophysiological studies were performed on rats on P65. The authors found a substantial reduction of hippocampal BDNF (n = 6 to 7) resulting from the transcriptional factors-mediated epigenetic modification in the promoter region of Bdnf exon IV in rats exposed postnatally to anesthetic drugs. This BDNF reduction led to the insufficient drive for the synthesis of synaptic proteins (n = 6 to 8), thus contributing to the hippocampal synaptic (n = 8 to 11) and cognitive dysfunction (n = 10) induced by neonatal anesthesia. These effects were mitigated by the exposure to an enriched environment. The findings of this study elucidated the epigenetic mechanism underlying memory deficiency induced by neonatal anesthesia and propose EE as a potential therapeutic approach.

  1. Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injury.

    Science.gov (United States)

    Wagenaar, Gerry T M; Laghmani, El Houari; de Visser, Yvonne P; Sengers, Rozemarijn M A; Steendijk, Paul; Baelde, Hans J; Walther, Frans J

    2013-02-15

    Ambrisentan, an endothelin receptor type A antagonist, may be a novel therapeutic agent in neonatal chronic lung disease (CLD) by blocking the adverse effects of the vasoconstrictor endothelin-1, especially pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We determined the cardiopulmonary effects of ambrisentan treatment (1-20 mg·kg(-1)·day(-1)) in neonatal rats with CLD in 2 models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included survival, lung and heart histopathology, right ventricular function, fibrin deposition, and differential mRNA expression in the lungs. In the early treatment model, we investigated the role of nitric oxide synthase (NOS) inhibition with N(ω)-nitro-L-arginine methyl ester (L-NAME; 25 mg·kg(-1)·day(-1)) during ambrisentan treatment. In the early treatment model, ambrisentan improved survival with reduced lung fibrin and collagen III deposition, arterial medial wall thickness, and RVH. These changes were not affected by L-NAME administration. Ambrisentan did not reduce the influx of macrophages and neutrophils or prevent reduced irregular elastin expression. In the late treatment model, ambrisentan diminished PAH, RVH, and right ventricular peak pressure, demonstrating that RVH is reversible in the neonatal period. Alveolarization and vascularization were not affected by ambrisentan. In conclusion, ambrisentan prolongs survival and reduces lung injury, PAH, and RVH via a NOS-independent mechanism but does not affect inflammation and alveolar and vascular development in neonatal rats with CLD.

  2. Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum.

    Science.gov (United States)

    Kimura-Kuroda, Junko; Nishito, Yasumasa; Yanagisawa, Hiroko; Kuroda, Yoichiro; Komuta, Yukari; Kawano, Hitoshi; Hayashi, Masaharu

    2016-10-04

    Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children's health. Here we examined the effects of longterm (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

  3. Anthraquinones and flavonoids of Cassia tora leaves ameliorate sodium selenite induced cataractogenesis in neonatal rats.

    Science.gov (United States)

    Sreelakshmi, V; Abraham, Annie

    2016-02-01

    The present study was undertaken to evaluate the efficacy of Cassia tora leaves, an edible plant traditionally used for eye ailments, in preventing experimental cataractogenesis. Cataract is the leading cause of irreversible visual impairment worldwide characterized by the cloudiness or opacification of the lens due to the disturbance of even distribution of lens proteins and lipids. A significant number of epidemiological studies have suggested the potential role of herbal medicine in the prevention of cataract by maintaining lens architecture. The study was conducted in neonatal rat pups of 8-10 days old with an ethyl acetate fraction of Cassia tora leaves (ECT) administered by gastric intubation. After 30 days, the animals were sacrificed and various parameters such as redox status and gene expressions were evaluated in lenses. ECT administration caused a significant decrease in the onset and maturation of cataract, potentiated antioxidant defense and normalized lens crystallin expression against cataract induced animals. HPLC and ESI-MS analysis of ECT revealed the presence of flavonoids and anthraquinones. Thus, the present study indicates the therapeutic potential of Cassia tora leaves in preventing cataract and the effect is endorsed by the presence of antioxidants in Cassia tora leaves.

  4. Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

    Directory of Open Access Journals (Sweden)

    Junko Kimura-Kuroda

    2016-10-01

    Full Text Available Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children’s health. Here we examined the effects of longterm (14 days and low dose (1 μM exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

  5. Neuroprotective effects of 17β-estradiol in a rat model of neonatal X radiation

    International Nuclear Information System (INIS)

    Caceres, L.G.; Aon, L.; Saraceno, E.; Capani, F.; Guelman, L.R.

    2009-01-01

    Developing Central Nervous System (CNS) is vulnerable to radiation-induced reactive oxygen species (ROS). The consequent oxidative stress has been shown to produce changes at behavioral, biochemical and histological levels in cerebellum (CE) and hippocampus (HIP). The aim of the present work was to test if 17β-estradiol, a potential neuroprotector, was able to counteract these changes. Neonatal male Wistar rats were X-irradiated (5 Gy) in their cephalic ends up to 48hs of postnatal life and a group of this animals was treated with 17β-estradiol (5 g/g). Open field (OF) test, ROS levels, as well as a histological assessment, were performed at 30 postnatal days. Administration of 17β-estradiol improved the short-term habituation and decreased the time spent in the centre in the OF. ROS levels returned to control in HIP and the cytoarchitecture of CE was reconstituted. These results suggest that 17β-estradiol was able to counteract the effects of X-rays at behavioral, biochemical and histological levels, probably acting through an antioxidant mechanism. (authors)

  6. Neonatal handling increases cardiovascular reactivity to contextual fear conditioning in borderline hypertensive rats (BHR).

    Science.gov (United States)

    Sanders, Brian J; Knoepfler, Jonathan

    2008-09-03

    Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR),which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1-14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92%+/-2.2 vs 80.7%+/-5.7, preturn to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease.

  7. Primary Culture of Choroid Plexuses from Neonate Rats Containing Progenitor Cells Capable of Differentiation

    Directory of Open Access Journals (Sweden)

    Sheng-Li Huang

    2013-12-01

    Full Text Available Background: The choroid plexuses, which could secrete a number of neurotrophins, have recently been used in transplantation in central nervous system diseases. Aims: To study the mechanism of nerve regeneration in the central nervous system by grafting choroid plexus tissues. Study Design: Animal experimentation. Methods: The choroid plexuses from the lateral ventricles of neonatal rats were cultured in adherent culture, and immunocytochemical methods were used to analyse the progenitor cells on days 2, 6, and 10 after seeding. Results: Expression of both nestin and glial fibrillary acidic protein was observed in small cell aggregates on day 2 in primary culture. Most of the nestin-positive cells on day 6 were immunoreactive to glial fibrillary acidic protein antibody. No cells expressing nestin or glial fibrillary acidic protein were seen on day 10. Conclusion: These experimental results indicate that the choroid plexus contains a specific cell population – progenitor cells. Under in vitro experimental conditions, the progenitor cells differentiated into choroid plexus epithelial cells but did not form neurons or astrocytes.

  8. Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Sheyda R Frolova

    Full Text Available The ability of azobenzene trimethylammonium bromide (azoTAB to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav, calcium (ICav, and potassium (IKv currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+ and calcium (Ca2+ currents and potentiation of net potassium (K+ currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential.

  9. Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats.

    Science.gov (United States)

    Jiao, Ke-Ping; Li, Shao-Min; Lv, Wen-Yan; Jv, Ming-Liang; He, Hai-Yan

    2017-06-14

    Vitamin D3 has been reported to be an immunity modulator and high levels of vitamin D3 are correlated with a decreased risk for developing diseases in the central nervous system. Astrocytes are important immune cells and contribute toward inflammation during neurological diseases. The vitamin D receptor has been reported to be expressed in astrocytes; however, the effect of vitamin D3 on astrocyte activation has not been studied. Here, we found that lipopolysaccharide stimulation in astrocytes could enhance the expression of vitamin D receptor and Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form. Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis factor-α, interleukin-1β, vascular endothelial growth factor, and also TLR4 in activated astrocytes. Astrocyte activation was further found to be suppressed after the administration of vitamin D3 in neonatal rats injected with lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin D3 in astrocytes after lipopolysaccharide stimulation. Considering the function of reactive astrocytes in augmenting inflammatory response in neurodegeneration and brain injury, the finding that vitamin D3 administration may inhibit astrocyte activation may be potentially useful for the treatment of central nervous system disorders.

  10. Effect of neonatal hypothyroidism on carbohydrate metabolism, insulin secretion, and pancreatic islets morphology of adult male offspring in rats.

    Science.gov (United States)

    Farahani, H; Ghasemi, A; Roghani, M; Zahediasl, S

    2013-01-01

    Neonatal hypothyroidism has serious effects on growth, development, and metabolism. This study aims to investigate the effects of the neonatal hypothyroidism on carbohydrate metabolism, islet insulin secretion and morphology of the pancreatic islets in adult male offspring. Lactating mothers of Wistar rats consumed 0.02% solution of 6-propyl-2-thiouracil during the weaning period (neonatal hypothyroid group), while mothers of the control group drank merely tap water. Body weight and survival of pups were followed up. Intravenous glucose tolerance test was performed in adult male offspring and 5-6 weeks later, glucose-stimulated insulin secretion (GSIS) was evaluated. During the glucose tolerance test, plasma glucose level of the neonatal hypothyroid group (13.18 ± 0.59 mmol/l) was significantly higher at 5 min compared to the control group (11.54 ± 0.47 mmol/l), whereas plasma insulin concentrations and GSIS of the groups was not significantly different. Homeostasis model assessment of insulin resistance of adult male offspring of the hypothyroid group (9.1 ± 1.0) was significantly higher as compared to the control group (4.5 ± 0.6). Area (14,613.0 ± 2646.3 μm2) and the diameter of the islets (147 ± 3.0 μm) of the neonatal hypothyroid group were significantly lower, as compared to the control group (32,886.3 ± 4690.3 and 206.6 ± 5.9 μm2 and μm, respectively). Neonatal hypothyroidism can alter carbohydrate metabolism in euthyroid adult offspring, which may increase susceptibility to the development of glucose intolerance and occurrence of Type 2 diabetes later in life.

  11. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T

    1995-01-01

    rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP...... revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallothionein-positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain......Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed...

  12. Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna Maria

    2016-08-31

    Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

  13. Postnatal thyroid hormone supplementation rescues developmental abnormalities induced by congenital-neonatal hypothyroidism in the rat retina.

    Science.gov (United States)

    Pinazo-Durán, Maria Dolores; Iborra, Francisco J; Pons, Sheila; Sevilla-Romero, Enrique; Gallego-Pinazo, Roberto; Muñoz, Alberto

    2005-01-01

    Thyroid hormones (TH) play a key role in central nervous system development. We have studied the influence of congenital and neonatal hypothyroidism on retinal development and the effects of postnatal TH supplementation. An experimental model was set up using Wistar rats by inducing chemical thyroidectomy during gestation and suckling. Eyes from control (CG) and TH-depleted (THDG) groups of animals were obtained at postnatal days 10 and 25. In the THDG, there was a significant reduction in the retinal thickness and layering, retinal volume, cell number and nuclear volumes in all layers. A third group of rats, made hypothyroid during the gestational and neonatal period and then supplemented with TH (THSG), showed a recovery of both the retinal thickness [at P25: 188.5 +/- 9.2 microm (THSG) vs. 175.8 +/- 16.1 microm (THDG), p < 0.001, and 210.8 +/- 8.9 (CG)] and total retinal cell number [at P25: 6.9 x 10(6) (THSG) vs. 3.7 x 10(6) (THDG) cells, p < 0.001, and 5.3 x 10(6) cells (CG)]. Light and electron microscopy studies confirmed that TH deprivation altered the organization of the retina, which was mostly normalized by hormone administration. Our data show that TH regulates intrinsic mechanisms for controlling retinal cytoarchitecture and layering, and that alterations in retinal maturation induced by congenital-neonatal TH deficiency can be at least partially rescued by early hormonal treatment in vivo.

  14. The expression of HoxB5 and SPC in neonatal rat lung after exposure to fluoxetine.

    Science.gov (United States)

    Taghizadeh, Razieh; Taghipour, Zahra; Karimi, Akbar; Shamsizadeh, Ali; Taghavi, Mohammad Mohsen; Shariati, Mahdi; Shabanizadeh, Ahmad; Jafari Naveh, Hamid Reza; Bidaki, Reza; Aminzadeh, Fariba

    2016-01-01

    Approximately 10% of pregnant women suffer from pregnancy-associated depression. Fluoxetine, as a selective serotonin reuptake inhibitor, is being employed as a therapy for depressive disorders. The present study aimed to determine the effects of fluoxetine on neonatal lung development. Thirty pregnant Wistar rats (weighing 200-250 g) were treated daily with 7 mg/kg fluoxetine from gestation day 0 to gestation day 21, via gavage. The control group received a similar volume of distilled water only. Following delivery, the newborns and their lungs were immediately weighed in both of the groups. The right lung was fixed for histological assessments while the left lung was used for evaluation of the expression of SPC and HoxB5 by the real-time polymerase chain reaction method. Results have indicated that even though the body weight and the number of neonatal rats in both groups were the same, the lung weight of neonates exposed to fluoxetine was significantly different compared to the control group ( P effects of antidepressant drugs during pregnancy is deserved.

  15. Tempol (4 hydroxy-tempo) inhibits anoxia-induced progression of mitochondrial dysfunction and associated neurobehavioral impairment in neonatal rats.

    Science.gov (United States)

    Samaiya, Puneet K; Narayan, Gopeshwar; Kumar, Ashok; Krishnamurthy, Sairam

    2017-04-15

    Anoxia leads to a robust generation of reactive oxygen species/nitrogen species which can result in mitochondrial dysfunction and associated cell death in the cerebral cortex of neonates. The present study investigated the pharmacological role of tempol in the treatment of rat neonatal cortical mitochondrial dysfunction induced insult progression (day-1 to day-7) and associated neurobehavioral alterations post-anoxia. Rat pups of 30h age or postnatal day 2 (PND2) were randomly divided into 5 groups (n=5 per group): (1) Control; (2) Anoxia; (3) Anoxia+Tempol 75mg/kg; (4) Anoxia+Tempol 150mg/kg; and (5) Anoxia+Tempol 300mg/kg, and subjected to two episode of anoxia (10min each) at 24h of time interval in an enclosed chamber supplied with 100% N 2 . Tempol significantly decreased nitric oxide (NO) formation and simultaneously improved superoxide dismutase (SOD) and catalase (CAT) activities. Further, we observed a significantly (Ptempol. Furthermore, tempol decreased expression of mitochondrial Bax, cytochrome-C, caspase-9 and caspase-3 while the increase in expression of cytoplasmic Bax, mitochondrial Bcl-2 on day-7 in cortical region indicating regulation of intrinsic pathway of apoptosis. Further, it improved anoxia-induced neurobehavioral outcome (hanging and reflex latencies). Biochemical, molecular and behavioral studies suggest the role of tempol in preserving mitochondrial function and associated neurobehavioral outcomes after neonatal anoxia. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.

    Science.gov (United States)

    Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

    2015-03-15

    Arginase is an enzyme that limits substrate L-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces L-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased L-arginine and L-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  17. Effects of rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia.

    Science.gov (United States)

    Ziino, Adrian J A; Ivanovska, Julijana; Belcastro, Rosetta; Kantores, Crystal; Xu, Emily Z; Lau, Mandy; McNamara, Patrick J; Tanswell, A Keith; Jankov, Robert P

    2010-02-01

    Rho-kinase (ROCK) inhibitors prevent pulmonary hypertension (PHT) in adult rodents, but little is known about their effects on the neonatal lung. Our objective was to examine the effects of ROCK inhibition on chronic hypoxia (CH)-induced PHT and abnormal lung structure in the neonatal rat. Pups were exposed to air or CH from postnatal d 1-14 while receiving Y-27632 (5 or 10 mg x kg(-1) x d(-1)), fasudil (20 mg x kg(-1) x d(-1)), or saline intraperitoneally. Relative to air, CH-exposed pups had increased pulmonary vascular resistance, right ventricular hypertrophy, arterial medial wall thickening, and abnormal distal airway morphology characterized by septal thinning and decreased secondary septation. Treatment with 10 mg/kg Y-27632 or fasudil attenuated the structural and hemodynamic changes of PHT while having no effect on septal thinning or inhibited secondary septation. In addition, Y-27632 (10 mg/kg) and fasudil augmented CH-induced somatic growth restriction. Pulmonary arteries of CH-exposed pups had increased ROCK activity, up-regulated expression of PDGF-BB and increased smooth muscle DNA synthesis, all of which were attenuated by treatment with 10 mg/kg Y-27632. Systemically administered ROCK inhibitors prevented PHT in the CH-exposed neonatal rat but at the cost of inhibited somatic growth. Limiting effects on vascular remodeling likely resulted, in major part, from attenuated vascular PDGF-BB/beta-receptor signaling.

  18. Disposition of low doses of {sup 14}C-bisphenol A in male, female, pregnant, fetal, and neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kurebayashi, Hideo; Ohno, Yasuo [National Institute of Health Sciences, Division of Pharmacology, Kamiyoga 1-18-1, Setagaya, Tokyo (Japan); Nagatsuka, Shin-Ichiro; Nemoto, Hiroyuki; Noguchi, Hideyo [Daiichi Pure Chemicals Co. Ltd, ADME/TOX Research Institute, 2117 Muramatsu, Tokai, Ibaraki (Japan)

    2005-05-01

    Bisphenol A (BPA) is a weak xenestrogen (ADI=50 {mu}g kg{sup -1}, US EPA) which is mass-produced, with potential for human exposure. To study absorption, distribution, excretion, and metabolism of BPA, BPA labeled with carbon-14 was administered p.o. to male and female Fischer (F344) rats at relatively low doses (20, 100, and 500 {mu}g kg{sup -1}), and i.v. injected at 100 and 500 {mu}g kg{sup -1}. {sup 14}C-BPA (500 {mu}g kg{sup -1}) was also administered orally to pregnant and lactating rats to examine the transfer of radioactivity to fetuses, neonatal rats, and milk. Radioluminographic determination using phosphor imaging plates was employed to achieve highly sensitive determination of radioactivity. Absorption ratios of radioactivity after three oral doses were high (35-82%); parent {sup 14}C-BPA in the circulating blood was quite low, however, suggesting considerable first-pass effect. After an oral dose of 100 {mu}g kg{sup -1} {sup 14}C-BPA, the radioactivity was distributed and eliminated rapidly, but remained in the intestinal contents, liver, and kidney for 72 h. The major metabolite in the plasma and urine was BPA glucuronide, whereas most of the BPA was excreted with the feces as free BPA. A second peak in the time-course of plasma radioactivity suggested enterohepatic recirculation of BPA glucuronide. There was limited distribution of {sup 14}C-BPA to the fetus and neonate after oral administration to the dam. Significant radioactivity was not detected in fetuses on gestation days 12 and 15. On day 18, however, radioactivity was detected in the fetal intestine and urinary bladder 24 h after oral dosing of {sup 14}C-BPA to the pregnant rats. Part of radioactivity was transferred to neonatal rats from the milk of the treated lactating dam and remained in the intestine of the neonates after 24-h nursing by an untreated dam. (orig.)

  19. The role of neonatal NMDA receptor activation in defeminization and masculinization of sex behavior in the rat

    Science.gov (United States)

    Schwarz, Jaclyn M.; McCarthy, Margaret M.

    2008-01-01

    Normal development of the male rat brain involves two distinct processes, masculinization and defeminization, that occur during a critical period of brain sexual differentiation. Masculinization allows for the capacity to express male sex behavior in adulthood, and defeminization eliminates or suppresses the capacity to express female sex behavior in adulthood. Despite being separate processes, both masculinization and defeminization are induced by neonatal estradiol exposure. Though the mechanisms underlying estradiol-mediated masculinization of behavior during development have been identified, the mechanisms underlying defeminization are still unknown. We sought to determine whether neonatal activation of glutamate NMDA receptors is a necessary component of estradiol-induced defeminization of behavior. We report here that antagonizing glutamate receptors during the critical period of sexual differentiation blocks estradiol-induced defeminization but not masculinization of behavior in adulthood. However, enhancing NMDA receptor activation during the same critical period mimics estradiol to permanently induce both defeminization and masculinization of sexual behavior. PMID:18687334

  20. Long-term alterations in peripheral taste responses to NaCl in adult rats following neonatal chorda tympani transection.

    Science.gov (United States)

    Martin, Louis J; Sollars, Suzanne I

    2015-02-01

    The peripheral taste system of the adult rodent is highly resilient against damage, with morphological, behavioral, and functional recovery evident after regeneration of a transected nerve. If chorda tympani transection (CTX) occurs at early postnatal ages however, the nerve fails to regenerate and effects on tongue morphology and behavior are more severe and longer-lasting compared to adult denervation. To examine whether neonatal CTX induces functional changes in intact nerves, whole-nerve electrophysiology was performed on the glossopharyngeal (GL) and chorda tympani (CT) nerves of adult rats that received CTX at P10. Attenuation of NaCl-elicited GL responses were observed in CTX rats 2 months after surgery, with bilateral denervation causing the largest decreases in responses. When assessed 1 year after neonatal CTX, amiloride-sensitive responses to NaCl in the contralateral CT increased while amiloride-insensitive responses decreased. Responses to other tastants were consistent with control animals. This is the first evidence of long-term functional changes to the peripheral taste system after injury in rats fed a normal diet. This study further characterizes the developing peripheral taste system as highly susceptible to change following neural injury. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. The Effect of Neonatal Leptin Antagonism in Male Rat Offspring Is Dependent upon the Interaction between Prior Maternal Nutritional Status and Post-Weaning Diet

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    Beltrand, J.; Sloboda, D. M.; Connor, K. L.; Truong, M.; Vickers, M. H.

    2012-01-01

    Epidemiological and experimental studies report associations between overweight mothers and increased obesity risk in offspring. It is unclear whether neonatal leptin regulation mediates this association between overweight mothers and offspring obesity. We investigated the effect of neonatal treatment with a leptin antagonist (LA) on growth and metabolism in offspring of mothers fed either a control or a high fat diet. Wistar rats were fed either a control (CON) or a high fat diet (MHF) durin...

  2. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

    Science.gov (United States)

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  3. Effects of Administration of Perinatal Bupropion on the Population Spike Amplitude in Neonatal Rat Hippocampal Slice

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    Soomaayeh Heysieat-talab

    2010-09-01

    Full Text Available Objective(sBupropion is an atypical antidepressant that is widely used in smoke cessation under FDA approval. The study of synaptic effects of bupropion can help to finding out its mechanism(s for stopping nicotine dependence. In this study the effects of perinatal bupropion on the population spike (PS amplitude of neonates were investigated. Materials and Methods Hippocampal slices were prepared from 18-25 days old rat pups. The experimental groups included control and bupropion-treated. Bupropion (40 mg/Kg, i.p. was applied daily in perinatal period as pre-treatment. Due to the studying acute effects, bupropion was also added to the perfusion medium (10, 50, 200 μM for 30 min. The evoked PS was recorded from pyramidal layer of CA1 area, following stimulation of Schaffer collaterals. ResultsA concentration of 10 μM bupropion had no significant effects on the PS amplitude. The 50 μM concentration of bupropion reduced the amplitude of responses in 50% of the studied cases. At a concentration of 200 μM, the recorded PS amplitudes were reduced in all slices (n= 22. Amplitude was completely abolished in 8 out of the 22 slices. The decrease of the PS amplitude was found to be more in the non-pre-treated slices than in the pre-treated slices when both were perfused with 200 μM bupropion.Conclusion The results showed the perinatal exposure to bupropion and its acute effects while indicating that at concentrations of 50 and 200 μM bupropion reduced the PS amplitude. It was also found that there was evidence of synaptic adaptation in comparison of bupropion-treated and non-treated slices whereas they were both perfused with 200 µM.

  4. Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers.

    Science.gov (United States)

    de Diego, Carlos; Chen, Fuhua; Xie, Yuanfang; Pai, Rakesh K; Slavin, Leonid; Parker, John; Lamp, Scott T; Qu, Zhilin; Weiss, James N; Valderrábano, Miguel

    2011-01-01

    Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Ca(i)) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CV(L)/CV(T), where CV(L) and CV(T) are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CV(L) and CV(T) proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CV(T) more than CV(L), increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Ca(i) chelator 1,2-bis oaminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.

  5. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

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    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  6. Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect.

    Science.gov (United States)

    Lopes-de-Morais, Andréia Albuquerque Cunha; Mendes-da-Silva, Rosângela Figueiredo; dos-Santos, Eryka Maria; Guedes, Rubem Carlos Araújo

    2014-12-03

    The use of dexamethasone (Dex) to treat chronic lung disease in preterm infants may produce adverse effects in the developing brain. Here, we evaluated the effects of neonatal Dex on the propagation of cortical spreading depression (CSD), and tested the action of vitamins C and E against the effect of Dex. Five groups of Wistar rats received, respectively: [1] no treatment (Naïve); [2] Vehicle (V); [3] tapering doses of Dex (Dex; 0.5mg/kg, 0.3mg/kg, and 0.1mg/kg) on postnatal day (PND) 1-3; [4] Dex plus 200mg/kg vitamin C and 100mg/kg vitamin E (DexCE); [5] only vitamins C and E (CE). Vehicle and vitamins were administered on PND 1-6. CSD was recorded after the pups reached maturity (PND 60-70). The Dex-treated group presented with higher CSD velocities (mean values ± SD, in mm/min: 4.14 ± 0.22, n=10) compared with the control groups (Naïve: 3.52 ± 0.13, n=8; V: 3.57 ± 0.18, n=10; CE: 3.51 ± 0.24, n=10; pVitamins C and E antagonized this effect (DexCE group; CSD velocity: 3.43 ± 0.12, n=9). No intergroup difference was observed concerning P-wave amplitude and duration. In all groups, after the cortex underwent CSD, the electrocorticogram (ECoG) amplitude increased approximately 50% compared with the baseline amplitude for the same animal (CSD-induced ECoG potentiation); however, no intergroup difference was observed. Data suggest that coadministration of antioxidant vitamins with Dex may be a helpful therapeutic strategy to reduce brain adverse effects of dexamethasone. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats.

    Science.gov (United States)

    Vlassaks, Evi; Strackx, Eveline; Vles, Johan Sh; Nikiforou, Maria; Martinez-Martinez, Pilar; Kramer, Boris W; Gavilanes, Antonio Wd

    2013-01-26

    Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult. In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines. Prenatally, FA induced acute downregulation in IL-1β, TNF-α and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls. FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy.

  8. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats.

    Science.gov (United States)

    Anholt, R R; De Souza, E B; Oster-Granite, M L; Snyder, S H

    1985-05-01

    We have developed a procedure that allows the autoradiographic localization of benzodiazepine receptors in whole-body sections of neonatal rats. Central-type benzodiazepine receptors, visualized with [3H]methylclonazepam, are restricted to nervous tissue. In contrast, peripheral-type benzodiazepine receptors, visualized with [3H]Ro5-4864, occur widely, but with discrete localizations throughout the body. Peripheral-type benzodiazepine receptors are most concentrated in the adrenal cortex and the skin. Substantial levels of these receptors are also evident in the heart, the salivary glands, discrete regions of the kidney, the epithelium of the lung, the nasal and lingual epithelia, the lining of the pulmonary arteries, the thymus, the hair follicles of the vibrissae, the tooth buds and the bone marrow. Considerable binding of [3H]Ro5-4864 is observed in the brown fat pads, the liver and the spleen, but high levels of nonspecific binding preclude accurate evaluation of the actual specific binding in these organs. Only low levels of [3H]Ro5-4864 binding sites are found in the brain and they are virtually undetectable in the skeletal muscle, the eye, the inner ear and the gastrointestinal tract. High levels of peripheral-type benzodiazepine receptor appear present in tissues that derive their metabolic energy primarily from oxidative phosphorylation, whereas only low levels are present in tissues that can derive their metabolic energy largely from glycogenolysis. Association of these receptors with mitochondria and a possible role in modulation of energy metabolism is suggested further by the observation that the histochemically visualized distribution of cytochrome oxidase activity overlaps the autoradiographic pattern of [3H]Ro5-4864 binding sites.

  9. Ethanol Influences on Bax Associations with Mitochondrial Membrane Proteins in Neonatal Rat Cerebellum

    Science.gov (United States)

    Heaton, Marieta Barrow; Siler-Marsiglio, Kendra; Paiva, Michael; Kotler, Alexandra; Rogozinski, Jonathan; Kubovec, Stacey; Coursen, Mary; Madorsky, Vladimir

    2012-01-01

    These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure, and focused on interactions between pro-apoptotic Bax and proteins of the permeability transition pore (PTP), voltage-dependent anion channel (VDAC), and adenine nucleotide translocator (ANT), of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that following ethanol exposure, Bax pro-apoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least two hours post-exposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment, and found such interactions were altered by ethanol treatment, but only at two-hours post-exposure, and only in the P4, ethanol-sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax, but not by a Bax channel blocker. Therefore, we conclude that at this age, within the constraints of our experimental model, a primary mode of Bax-induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex, and not channel formation independent of PTP constituents. PMID:22767450

  10. Maternal and neonatal dietary intake of balanced n-6/n-3 fatty acids modulates experimental colitis in young adult rats.

    Science.gov (United States)

    Reddy, K Vijay Kumar; Naidu, K Akhilender

    2016-08-01

    The imbalance of n-6 and n-3 polyunsaturated fatty acids in the maternal diet impairs intestinal barrier development and sensitizes the colon response to inflammatory insults in the young rats. With a view to overcoming this issue, we designed this study to investigate the effect of maternal and neonatal intake of different proportions of n-6/n-3 fatty acids on colon inflammation in the young adult rats. Female Wistar rats were assigned into four groups, and each group fed one of four semisynthetic diets, namely n-6, low n-3, n-6/n-3 and n-3 fatty acids for 8 weeks prior to mating, during gestation and lactation periods. At weaning, the pups were separated from the dams and fed diet similar to the mothers. Colitis was induced on postnatal day 35, by administering 2 % dextran sulfate sodium in drinking water for 10 days. Colitis was assessed based on the clinical and inflammatory markers in the colon. Fatty acid analysis was done in liver, RBC, colon and spleen. A balanced n-6/n-3 PUFA diet significantly improved the body weight loss, rectal bleeding and mortality in rats. This was associated with lower myeloperoxidase activity, nitric oxide, prostaglandin E2, TNF-α and IL-6, IL-8, COX-2 and iNOS levels in the colon tissues. Fatty acid analysis has shown that the arachidonic acid/docosahexaenoic acid ratio was significantly lower in liver, RBC, colon and spleen in n-6/n-3 and n-3 diet groups. We demonstrate that balanced n-6/n-3 PUFA supplementation in maternal and neonatal diet alters systemic AA/DHA ratio and attenuates colon inflammation in the young adult rats.

  11. Effects of maternal separation on behavior and brain damage in adult rats exposed to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Tata, Despina A; Markostamou, Ioanna; Ioannidis, Anestis; Gkioka, Mara; Simeonidou, Constantina; Anogianakis, Georgios; Spandou, Evangelia

    2015-03-01

    Animal studies suggest that maternal separation, a widely used paradigm to study the effects of early life adversity, exerts a profound and life-long impact on both brain and behavior. The aim of the current study was to investigate whether adverse early life experiences interact with neonatal hypoxia-ischemia, affecting the outcome of this neurological insult at both functional and structural levels during adulthood. Rat pups were separated from their mothers during postnatal days 1-6, for either a short (15 min) or prolonged (180 min) period, while another group was left undisturbed. On postnatal day 7, a subgroup from each of the three postnatal manipulations was exposed to a hypoxic-ischemic episode. Behavioral examination took place approximately at three months of age and included tests of learning and memory (Morris water maze, novel object and novel place recognition), as well as motor coordination (rota-rod). We found that both prolonged maternal separation and neonatal hypoxia-ischemia impaired the animals' spatial learning and reference memory. Deficits in spatial but not visual recognition memory were detected only in hypoxic-ischemic rats. Interestingly, prolonged maternal separation prior to neonatal hypoxia-ischemia augmented the reference memory impairments. Histological analysis of infarct size, hippocampal area and thickness of corpus callosum did not reveal any exacerbation of damage in hypoxic-ischemic rats that were maternally separated for a prolonged period. These are the first data suggesting that an adverse postnatal environmental manipulation of just 6 days causes long-term effects on spatial learning and memory and may render the organism more vulnerable to a subsequent insult. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.

    Science.gov (United States)

    Ceprián, Maria; Jiménez-Sánchez, Laura; Vargas, Carlos; Barata, Lorena; Hind, Will; Martínez-Orgado, Jose

    2017-04-01

    and purpose: Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS). Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke. The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS. Middle Cerebral Artery Occlusion (MCAO) was achieved in neonatal Wistar rats by introducing a nylon filament to the left MCA for 3 h; 15 min after removing the occluder vehicle (MCAO-V) or CBD single dose 5 mg/kg (MCAO-C) were administered i. p. Similarly manipulated but non-occluded rats served as controls (SHM). A set of behavioral tests was then conducted one week (P15) or one month (P38) after MCAO. Brain damage was then assessed by magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (H + -MRS) and histologic (TUNEL for cell death, immunohistochemistry for neuron, astrocyte and microglia identification) studies. CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H + -MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation. CBD administration after MCAO led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  14. Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone β-Subunit in Peripubertal Male Rats

    Directory of Open Access Journals (Sweden)

    Pilar Argente-Arizón

    2018-04-01

    Full Text Available Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition or 12 pups (controls per dam. Leptin was administered sc (3 µg/g body weight at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but

  15. Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide.

    Science.gov (United States)

    Kaizaki, Asuka; Tien, Lu-Tai; Pang, Yi; Cai, Zhengwei; Tanaka, Sachiko; Numazawa, Satoshi; Bhatt, Abhay J; Fan, Lir-Wan

    2013-04-05

    Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in the inflammatory process. The objective of the current study was to examine whether celecoxib, a selective COX-2 inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction and sensorimotor behavioral impairments. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in rat pups on postnatal Day 5 (P5), and celecoxib (20 mg/kg) or vehicle was administered (i.p.) five minutes after LPS injection. Sensorimotor behavioral tests were carried out 24 h after LPS exposure, and brain injury was examined on P6. Our results showed that LPS exposure resulted in impairment in sensorimotor behavioral performance and injury to brain dopaminergic neurons, as indicated by loss of tyrosine hydroxylase (TH) immunoreactivity, as well as decreases in mitochondria activity in the rat brain. LPS exposure also led to increases in the expression of α-synuclein and dopamine transporter proteins and enhanced [3H]dopamine uptake. Treatment with celecoxib significantly reduced LPS-induced sensorimotor behavioral disturbances and dopaminergic neuronal dysfunction. Celecoxib administration significantly attenuated LPS-induced increases in the numbers of activated microglia and astrocytes and in the concentration of IL-1β in the neonatal rat brain. The protective effect of celecoxib was also associated with an attenuation of LPS-induced COX-2+ cells, which were double labeled with TH + (dopaminergic neuron) or glial fibrillary acidic protein (GFAP) + (astrocyte) cells. Systemic LPS administration induced brain inflammatory responses in neonatal rats; these inflammatory responses included induction of COX-2 expression in TH neurons and astrocytes. Application of the COX-2 inhibitor celecoxib after LPS treatment attenuated the inflammatory response and improved LPS-induced impairment

  16. Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.

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    Ihssane Zouikr

    Full Text Available Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis during postnatal day (PND 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG as well as rostral and caudal axes of the ventrolateral PAG (VLPAG. Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb as compared to medial habenula (MHb, however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

  17. Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

    Science.gov (United States)

    Zouikr, Ihssane; James, Morgan H.; Campbell, Erin J.; Clifton, Vicki L.; Beagley, Kenneth W.; Dayas, Christopher V.; Hodgson, Deborah M.

    2014-01-01

    Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. PMID:24878577

  18. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  19. Biosynthesis of vitamin C stabilized tin oxide nanoparticles and their effect on body weight loss in neonatal rats.

    Science.gov (United States)

    Yang, Jie; Yang, Ke-Qing; Qiu, Li

    2017-09-01

    The green synthesis of tin oxide nanoparticles (SnO 2 NPs) using vitamin C (Vc) as a reducing agent via a biosynthetic approach is described. The effect of Vc-stabilized SnO 2 NPs on the body weight of neonatal rats is also studied. The prepared SnO 2 NPs were characterized using spectroscopic and microscopic instrumental techniques including transmission electron microscopy (TEM), UV-visible spectrophotometry (UV-vis), X-ray diffraction and Fourier transform infrared spectroscopy, which confirmed the formation of NPs. TEM images confirmed the formation of spherical NPs with a mean particle size of around 30nm. The body weight studies showed that vitamin-C stabilized SnO 2 NPs promote a higher body weight gain compared to raw SnO 2 NPs. It was also shown that Vc can counteract the decreased body weight caused by SnO 2 NPs in neonatal rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

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    Jennifer E Bruin

    Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

  1. Stroma cell-derived factor-1α signaling enhances calcium transients and beating frequency in rat neonatal cardiomyocytes.

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    Ielham Hadad

    Full Text Available Stroma cell-derived factor-1α (SDF-1α is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R blocker, but not with a ryanodine receptor (RyR antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.

  2. Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against Hyperoxic Lung Injury in a Neonatal Rat Model.

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    Merih Cetinkaya

    Full Text Available Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA, a histone deacetylase (HDAC inhibitor, on neonatal hyperoxic lung injury.Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated.VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+ cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions.The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.

  3. Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats.

    Science.gov (United States)

    Chiarotto, Gabriela Bortolança; Drummond, Luisa; Cavarretto, Gabriela; Bombeiro, André Luis; de Oliveira, Alexandre Leite Rodrigues

    2014-07-01

    Peripheral nerve injury in newborn rats triggers extensive neuronal death within the spinal cord. Because most neurodegeneration is related to oxidative stress and apoptosis, the use of antioxidants may be of therapeutic interest. Tempol is promising because of its ability to chelate reactive oxygen species and to minimize or even prevent tissue damage. Here, we evaluated neuroprotective effects of tempol following neonatal sciatic nerve transection. Two-day-old pups underwent sciatic nerve axotomy followed by tempol (12, 24 and 48 mg/kg) treatment (i.p.) at 10 min, 6 h, and every 24 h up to 1 week after injury. The rats were then killed for lumbar intumescence analysis. Nissl staining, TUNEL, synaptophysin immunolabeling and qRT-PCR (Caspase 3, Bax and Bcl2) were carried out. The results indicated that tempol treatment, at 24 mg/kg, increased up to 21% spinal cord motoneuron survival (ptempol-treated animals. qRT-PCR results indicated differential increase in Caspase 3 (3-fold), Bax (13-fold) and Bcl2 (28-fold) gene expression, after 12 h following axotomy and tempol treatment. In conclusion, tempol administration has proven to be neuroprotective after neonatal nerve injury, leading to improved motoneuron survival, synapse preservation and minimizing apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Role of dopamine D2 receptors in ischemia/reperfusion induced apoptosis of cultured neonatal rat cardiomyocytes

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    Zhao Ya-jun

    2011-02-01

    Full Text Available Abstract Background Myocardial ischemia/reperfusion injury is the major cause of morbidity and mortality for cardiovascular diseases. Dopamine D2 receptors are expressed in cardiac tissues. However, the roles of dopamine D2 receptors in myocardial ischemia/reperfusion injury and cardiomyocyte apoptosis are unclear. Here we investigated the effects of both dopamine D2 receptors agonist (bromocriptine and antagonist (haloperidol on apoptosis of cultured neonatal rat ventricular myocytes induced by ischemia/reperfusion injury. Methods Myocardial ischemia/reperfusion injury was simulated by incubating primarily cultured neonatal rat cardiomyocytes in ischemic (hypoxic buffer solution for 2 h. Thereafter, these cells were incubated for 24 h in normal culture medium. Results Treatment of the cardiomyocytes with 10 μM bromocriptine significantly decreased lactate dehydrogenase activity, increased superoxide dismutase activity, and decreased malondialdehyde content in the culture medium. Bromocriptine significantly inhibited the release of cytochrome c, accumulation of [Ca2+]i, and apoptosis induced by ischemia/reperfusion injury. Bromocriptine also down-regulated the expression of caspase-3 and -9, Fas and Fas ligand, and up-regulated Bcl-2 expression. In contrast, haloperidol (10 μM had no significant effects on the apoptosis of cultured cardiomyocytes under the aforementioned conditions. Conclusions These data suggest that activation of dopamine D2 receptors can inhibit apoptosis of cardiomyocytes encountered during ischemia/reperfusion damage through various pathways.

  5. The effects of ionizing radiation in the rat's mandibular bone freeding the hypernomic calcium-deficient diet

    International Nuclear Information System (INIS)

    Hasegawa, Gen; Kurita, Akihiko; Nasu, Masanori; Furumoto, Keiichi

    1994-01-01

    The mandibles of rats in a group maintained on the Ca-deficient diet for a long period were irradiated with 30 Gy. To study the effects of radiation, serum Ca and inorganic phosphorus levels were determined for 3 weeks, and the data were compared with findings obtained from rats maintained on a standard diet by autoradiography using 45 Ca and microradiography. The serum Ca level tended to decrease with time after irradiation in the irradiated group maintained on the Ca-deficient diet, but there was no significant difference between the group maintained on the Ca-deficient diet and the group maintained on the standard diet. The serum inorganic phosphorus levels were almost constant throughout the observation period in both the non-irradiated and radiated groups regardless of diet. Uptake of 45 Ca was examined by autoradiography. Both the non-irradiated and irradiated groups maintained on the Ca-deficient diet showed intense 45 Ca uptake, there was almost no difference between these groups in photographic density or in weekly changes after irradiation. The microradiographic study of bone trabeculae revealed only slight changes in the bone cortex after irradiation in the group maintained on the standard diet. On day 3 after irradiation both thinning and roughness of the trabeculae were observed in the interradicular septa and incisal inferior margin and on day 7 in cancellous bone. In the groups maintained on the Ca-deficient diet, marked thinning and roughness of the trabeculae were observed mainly in the cancellous bone. (author)

  6. Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

    Science.gov (United States)

    Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

  7. Neurogenesis Recovery Induced by Granulocyte-colony Stimulating Factor in Neonatal Rat Brain After Perinatal Hypoxia

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    Yung-Ning Yang

    2013-12-01

    Conclusion: This study suggests that G-CSF may be a potentially beneficial therapy, at least in part, through universal recovery of neurogenesis effects in the neonatal brain after perinatal hypoxia insult.

  8. Identification of Retinopathy of Prematurity Related miRNAs in Hyperoxia-Induced Neonatal Rats by Deep Sequencing

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    Ruibin Zhao

    2014-12-01

    Full Text Available Retinopathy of prematurity (ROP remains a major problem for many preterm infants. MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level and have been studied in many diseases. To understand the roles of miRNAs in ROP model rats, we constructed two small RNA libraries from the plasma of hyperoxia-induced rats and normal controls. Sequencing data revealed that 44 down-regulated microRNAs and 22 up-regulated microRNAs from the hyperoxia-induced rats were identified by deep sequencing technology. Some of the differentially expressed miRNAs were confirmed by quantitative reverse transcription-PCR (qRT-PCR. A total of 594 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in angiogenesis, cell proliferation and cell differentiation, which might be involved in the genesis and development of ROP. The elevated expression level of the vascular endothelial growth factor (VEGF protein in the hyperoxia-induced neonatal rats was also confirmed by enzyme linked immunosorbent assay (ELISA. This study provides some insights into the molecular mechanisms that underlie ROP development, thereby aiding the diagnosis and treatment of this disease.

  9. Neonatal exposure of rats to antidepressants affects behavioral reactions to novelty and social interactions in a manner analogous to autistic spectrum disorders.

    Science.gov (United States)

    Rodriguez-Porcel, Federico; Green, Donald; Khatri, Nidhi; Harris, Sharonda Swilley; May, Warren L; Lin, Rick C S; Paul, Ian A

    2011-10-01

    We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty, and impairs social interactions in a manner similar to that observed in ASD. Male and female Long-Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8-21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2× for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32-P34) and later, we assessed sexual response to an estrus female in male rats (P153-184). Antidepressant exposure increased freezing after tone, diminished novel object exploration, and reduced conspecific interaction up to 3× compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant-exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD. Copyright © 2011 Wiley-Liss, Inc.

  10. The Effect of Neonatal Leptin Antagonism in Male Rat Offspring Is Dependent upon the Interaction between Prior Maternal Nutritional Status and Post-Weaning Diet

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    J. Beltrand

    2012-01-01

    Full Text Available Epidemiological and experimental studies report associations between overweight mothers and increased obesity risk in offspring. It is unclear whether neonatal leptin regulation mediates this association between overweight mothers and offspring obesity. We investigated the effect of neonatal treatment with a leptin antagonist (LA on growth and metabolism in offspring of mothers fed either a control or a high fat diet. Wistar rats were fed either a control (CON or a high fat diet (MHF during pregnancy and lactation. Male CON and MHF neonates received either saline (S or a rat-specific pegylated LA on days 3, 5, and 7. Offspring were weaned onto either a control or a high fat (hf diet. At day 100, body composition, blood glucose, β-hydroxybutyrate and plasma leptin and insulin were determined. In CON and MHF offspring, LA increased neonatal bodyweights compared to saline-treated offspring and was more pronounced in MHF offspring. In the post-weaning period, neonatal LA treatment decreased hf diet-induced weight gain but only in CON offspring. LA treatment induced changes in body length, fat mass, body temperature, and bone composition. Neonatal LA treatment can therefore exert effects on growth and metabolism in adulthood but is dependent upon interactions between maternal and post-weaning nutrition.

  11. Maternal low-level lead exposure reduces the expression of PSA-NCAM and the activity of sialyltransferase in the hippocampi of neonatal rat pups.

    Science.gov (United States)

    Hu, Qiansheng; Fu, Hongjun; Ren, Tieling; Wang, Shuyu; Zhou, Wei; Song, Hong; Han, Yifan; Dong, Shengzhang

    2008-07-01

    Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for cell migration and neurite outgrowth. Developmental lead (Pb) exposure has been considered to affect the expression of PSA-NCAM, which contributes to the neurotoxicity of Pb exposure. However, the effect of maternal low-level Pb exposure on the expression of PSA-NCAM in neonatal rat pups has not been reported. In the present study, female Wistar rats were exposed to vehicle or different dosages of lead chloride (0.5-4mM PbCl2) 2 weeks before and during pregnancy. This exposure protocol resulted in neonatal rat pups blood Pb levels up to 12.12+/-0.38 microg/dl, and hippocampal Pb levels up to 9.22+/-0.81 microg/g at postnatal day 1 (PND 1). Immunohistochemistry analysis and Western blot analysis revealed that the expressions of PSA-NCAM and NCAM in the hippocampi of neonatal rat pups at PND 1 were significantly reduced by the maternal low-level Pb exposures. Furthermore, the mRNA levels of NCAM and polysialyltransferases (STX and PST), measured by the fluorescent real-time quantitative RT-PCR, dosage-dependently and significantly decreased by 13.26-37.62%, 25.17-59.67%, and 10.78-47.81%, respectively. In addition, the sialyltransferase activity in neonatal rat pups was significantly reduced by 6.23-32.50% in the presence of the low-level Pb exposure, too. Taken together, these results suggest that maternal low-level Pb exposure reduces the expression of PSA-NCAM, NCAM, and the activity of sialyltransferase in the hippocampi of neonatal rat pups, which might contribute to the learning and memory impairments in the developmental pups following maternal low-level Pb exposure.

  12. The effects of ionizing radiation in the rat's mandibular bone freeding the hypernomic calcium-deficient diet

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Gen; Kurita, Akihiko; Nasu, Masanori; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-06-01

    The mandibles of rats in a group maintained on the Ca-deficient diet for a long period were irradiated with 30 Gy. To study the effects of radiation, serum Ca and inorganic phosphorus levels were determined for 3 weeks, and the data were compared with findings obtained from rats maintained on a standard diet by autoradiography using [sup 45]Ca and microradiography. The serum Ca level tended to decrease with time after irradiation in the irradiated group maintained on the Ca-deficient diet, but there was no significant difference between the group maintained on the Ca-deficient diet and the group maintained on the standard diet. The serum inorganic phosphorus levels were almost constant throughout the observation period in both the non-irradiated and radiated groups regardless of diet. Uptake of [sup 45]Ca was examined by autoradiography. Both the non-irradiated and irradiated groups maintained on the Ca-deficient diet showed intense [sup 45]Ca uptake, there was almost no difference between these groups in photographic density or in weekly changes after irradiation. The microradiographic study of bone trabeculae revealed only slight changes in the bone cortex after irradiation in the group maintained on the standard diet. On day 3 after irradiation both thinning and roughness of the trabeculae were observed in the interradicular septa and incisal inferior margin and on day 7 in cancellous bone. In the groups maintained on the Ca-deficient diet, marked thinning and roughness of the trabeculae were observed mainly in the cancellous bone. (author).

  13. Systemic Injection of Low-Dose Lipopolysaccharide Fails to Break down the Blood–Brain Barrier or Activate the TLR4-MyD88 Pathway in Neonatal Rat Brain

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    Peng Wang

    2014-06-01

    Full Text Available We aimed to investigate whether peripheral low-dose lipopolysaccharide (LPS induces the breakdown of the blood–brain barrier (BBB and/or the activation of toll-like receptor 4 (TLR4 in the neonatal rat brain. Neonatal rats received intraperitoneal injections of low-dose LPS (0.3 mg/kg∙bw, and the BBB compromise was detected by Evans Blue extravasation and electron microscopy. Meanwhile, TLR4, adaptin myeloid differentiation factor 88 (MyD88, nuclear transcription factor kappa-B (NF-κB p50 and tumor necrosis factor alpha (TNFα in the neonatal rat brain were determined by quantitative real-time polymerase chain reaction (PCR and Western Blot. Immunohistochemistry was used to determine the distribution and activation of microglia in the brain after LPS administration. It was demonstrated that Evans Blue extravasation was not observed in the brain parenchyma, and that tight junctions of cerebral endothelial cells remained intact after systemic injections of LPS in neonatal rats. Although intracerebroventricular injections of LPS activated microglia and up-regulated the expression of TLR4, MyD88, NF-κB p50 and TNFα in the neonatal rat brain, systemic LPS did not induce these responses. These findings indicate that while the neonatal rat brain responds to the direct intra-cerebral administration of LPS through robust TLR4 activation, systemic low-dose LPS does not induce the innate immune reaction or compromise the BBB in neonatal rats.

  14. Ultrasound stimulation of mandibular bone defect healing

    NARCIS (Netherlands)

    Schortinghuis, Jurjen

    2004-01-01

    The conclusions of the experimental work presented in this thesis are: 1. Low intensity pulsed ultrasound is not effective in stimulating bone growth into a rat mandibular defect, either with or without the use of osteoconductive membranes. 2. Low intensity pulsed ultrasound does not seem to have an

  15. The expression of HoxB5 and SPC in neonatal rat lung at exposure to fluoxetine

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    Taghizadeh R

    2016-11-01

    Full Text Available Razieh Taghizadeh,1 Zahra Taghipour,2 Akbar Karimi,1 Ali Shamsizadeh,3 Mohammad Mohsen Taghavi,2 Mahdi Shariati,2 Ahmad Shabanizadeh,2 Hamid Reza Jafari Naveh,2 Reza Bidaki,4 Fariba Aminzadeh51Department of Biology, Payame Noor University, Isfahan, Iran; 2Department of Anatomy, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; 3Department of Physiology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; 4Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 5Rafsanjan University of Medical Sciences, Rafsanjan, IranObjective: Approximately 10% of pregnant women suffer from pregnancy-associated depression. Fluoxetine, as a selective serotonin reuptake inhibitor, is being employed as a therapy for depressive disorders. The present study aimed to determine the effects of fluoxetine on neonatal lung development.Methods: Thirty pregnant Wistar rats (weighing 200–250 g were treated daily with 7 mg/kg fluoxetine from gestation day 0 to gestation day 21, via gavage. The control group received a similar volume of distilled water only. Following delivery, the newborns and their lungs were immediately weighed in both of the groups. The right lung was fixed for histological assessments while the left lung was used for evaluation of the expression of SPC and HoxB5 by the real-time polymerase chain reaction method.Results: Results have indicated that even though the body weight and the number of neonatal rats in both groups were the same, the lung weight of neonates exposed to fluoxetine was significantly different compared to the control group (P<0.05. Expression of both genes was increased, nonetheless, only elevation of HoxB5 was significant (P<0.05. Histological studies demonstrated that lung tissue in the fluoxetine treatment group morphologically appears to be similar to the pseudoglandular phase, whereas the control group lungs experienced more development.Conclusion: According to the upregulated expression of HoxB5 concerning

  16. A new method for continuous, long-term polysomnographic recording of neonatal rats.

    Science.gov (United States)

    Feng, P; Vogel, G W

    2000-02-01

    Many findings suggest that in altricial mammals neonatal REM sleep has developmental functions. However, investigations of these developmental functions has been hampered by technical limitations of the conventional polysomnographic (PSG) recording technique. One limitation is that continuous (24 hour/day), long-term (weeks) PSG recordings have not been achieved. A second limitation is that the metal screw electrodes and head plugs cemented to the skull cannot be removed to allow the neonate to mature into adulthood. As a result of these limitations, the relationship between neonatal sleep/wake variables and adult variables has not been studied. Also the effects of polysomnographically controlled neonatal REM sleep deprivation on adult variables have not been studied. The present work describes a new technique called the soft head plug (SH) method for continuous, long-term PSG recording. In the new technique, electrodes are thin, strong, Teflon wires that are led by a suturing needle through the soft skull to the epidural space, then with a U-turn exited from the skull and tied to the entry wire. Thus, in contrast to the conventional technique, the soft head plug technique does not use screws as electrodes and does not cement a hard, relatively large electrode plug to the skull, removal of which is fatal or very traumatic. The SH recording electrodes can be removed without damage to neonates. NA. NA. NA. In the present study sleep/wake results with the soft head plug technique were reliable (replicated) and, compared with results of the conventional method, valid. The results indicate that the soft head plug technique can be used to study relationships between neonatal sleep/wake variables and adult variables.

  17. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Science.gov (United States)

    Bañales-Martínez, Luis R.; Lemus-Varela, María de Lourdes; Trujillo, Xóchitl; Sánchez-Parada, María G.; Armendáriz-Borunda, Juan; Zúñiga-González, Guillermo M.

    2016-01-01

    Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects. PMID:28018917

  18. Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Caballero, Miguel; Núñez, Fabiana; Ahern, Siobhán; Cuffí, Maria L; Carbonell, Lourdes; Sánchez, Silvia; Fernández-Dueñas, Víctor; Ciruela, Francisco

    2011-04-20

    Nowadays the pharmacological treatment of the attention deficit hyperactivity disorder (ADHD) is based on amphetamine derivatives (i.e. methylphenidate). However, these drugs induce a large array of adverse side effects, thus less aggressive psychostimulant drugs (i.e. caffeine) are being proposed in the management of ADHD. Following this tendency, we decided to study the possible therapeutic use of caffeine in an animal model of ADHD, namely the neonatal 6-hydroxy-dopamine (6-OHDA)-lesioned rat. Therefore, at postnatal day 7 rats were lesioned at the left striatum with 6-OHDA or with saline. Thereafter, at postnatal day 25 their activity and attention were measured with the Olton maze before caffeine was administered ad libitum in the drinking water. Next, after 14 days of caffeine treatment, we repeated these measurements to assess the effect of caffeine on motor activity and attention deficit. Interestingly, while no changes in the motor activity measurements were observed before and after caffeine administration, a significant improvement in the attention deficit of the 6-OHDA lesioned rats was achieved after caffeine treatment. Thus, our results led us to hypothesize that caffeine might be useful to manage the attention deficit during the prepubertal period of ADHD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Directory of Open Access Journals (Sweden)

    Belinda C. Gómez-Meda

    2016-01-01

    Full Text Available Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs and micronucleated polychromatic erythrocytes (MNPCEs in the samples from pups in the experimental groups (P<0.02 and increased MNPCE frequencies in the samples from the dams (P<0.05. These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.

  20. [Effect of leptin on expression of calpain-1 and Bcl-2 and apoptosis in myocardial tissue of neonatal rats after asphyxia].

    Science.gov (United States)

    Wu, Dan-Dan; Wu, Xing-Heng; Zhang, Li-Na

    2016-10-01

    To study the effect of leptin on the expression of calcium-activated neutral protease 1 (calpain-1) and B cell lymphoma-2 (Bcl-2) and apoptosis in the myocardial tissue of neonatal rats after asphyxia. A total of 48 neonatal rats were randomly and equally divided into normal control group, asphyxia group, leptin treatment groups, and calpain-1 inhibitor (CAI-1) group. The neonatal rat model of asphyxia under normal atmospheric condition was established in all groups except the control group. For the leptin treatment groups, rats received 20, 80, and 160 μg/kg leptin by intraperitoneal injection immediately after model establishment, respectively. For the CAI-1 group, rats received 10 mg/kg CAI-1 by intraperitoneal injection immediately after model establishment. For all the groups, the myocardial tissue was collected at 2 hours after model establishment. Immunohistochemistry was used to measure the expression of calpain-1 and Bcl-2. The TUNEL method was used to evaluate apoptosis of myocardial cells. The expression of calpain-1 and Bcl-2 and apoptosis index (AI) were significantly higher in the asphyxia group than in the normal control group (P˂0.05). The leptin treatment groups and the CAI-1 group had significantly lower expression of calpain-1, significantly lower AI, and significantly higher expression of Bcl-2 than the asphyxia group (P˂0.05). The CAI-1 group had the largest changes in all the indices compared with the asphyxia group. However, there were no significant differences in all indices between the 160 μg/kg leptin treatment group and the CAI-1 group. After asphyxia, the expression of calpain-1 was positively correlated with AI, while the expression of Bcl-2 was negatively correlated with AI and the expression of calpain-1 (P˂0.05). Leptin reduces apoptosis of myocardial cells in asphyxiated neonatal rats by the inhibition of calpain-1 activation and upregulation of Bcl-2 expression.

  1. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-01-01

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

  2. Identification and functionality of proteomes secreted by rat cardiac stem cells and neonatal cardiomyocytes

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Chimenti, I.; Marban, E.; Van Eyk, J.E.

    2010-01-01

    Roč. 10, č. 2 (2010), s. 245-253 ISSN 1615-9853 Institutional research plan: CEZ:AV0Z40310501 Keywords : animal proteomics * cardiac stem cells * neonatal cardiomyocytes Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.815, year: 2010

  3. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response

    NARCIS (Netherlands)

    Chen, Xueyu; Walther, Frans J; Sengers, Rozemarijn M A; Laghmani, El Houari; Salam, Asma; Folkerts, Gert; Pera, Tonio; Wagenaar, Gerry T M

    2015-01-01

    Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic

  4. Effect of neonatal dentate gyrus lesion on allothetic and idiothetic navigation in rats

    Czech Academy of Sciences Publication Activity Database

    Czéh, B.; Stuchlík, Aleš; Wesierska, Malgorzata; Cimadevilla, Jose Maria; Pokorný, J.; Seress, L.; Bureš, Jan

    2001-01-01

    Roč. 75, č. 2 (2001), s. 190-213 ISSN 1074-7427 R&D Projects: GA ČR GA309/97/0555; GA ČR GA309/00/1656 Institutional research plan: CEZ:AV0Z5011922 Keywords : spatial memory * neonatal brain damage * hippocampus Subject RIV: FH - Neurology Impact factor: 1.830, year: 2001

  5. Aluminum alters NMDA receptor 1A and 2A/B expression on neonatal hippocampal neurons in rats

    Directory of Open Access Journals (Sweden)

    Yuan Chia-Yi

    2011-11-01

    Full Text Available Abstract Background High aluminum (Al content in certain infant formula raises the concern of possible Al toxicity on brain development of neonates during their vulnerable period of growing. Results of in vivo study showed that Al content of brain tissues reached to 74 μM when oral intake up to 1110 μM, 10 times of that in the hi-Al infant formula. Methods Utilizing a cultured neuron cells in vitro model, we have assessed Al influence on neuronal specific gene expression alteration by immunoblot and immunohistochemistry and neural proliferation rate changes by MTT assay. Results Microscopic images showed that the neurite outgrowth of hippocampal neurons increased along with the Al dosages (37, 74 μM Al (AlCl3. MTT results also indicated that Al increased neural cell viability. On the other hand, the immunocytochemistry staining suggested that the protein expressions of NMDAR 1A and NMDAR 2A/B decreased with the Al dosages (p Conclusion Treated hippocampal neurons with 37 and 74 μM of Al for 14 days increased neural cell viability, but hampered NMDAR 1A and NMDAR 2A/B expressions. It was suggested that Al exposure might alter the development of hippocampal neurons in neonatal rats.

  6. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Science.gov (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  7. Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.

    Science.gov (United States)

    Gien, Jason; Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H

    2016-12-01

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ET A (BQ123/BQ610) and ET B (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1-ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. Copyright © 2016 the American Physiological Society.

  8. Evidence that the periaqueductal gray matter mediates the facilitation of panic-like reactions in neonatally-isolated adult rats.

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    Jeyce Willig Quintino-dos-Santos

    Full Text Available Plenty of evidence suggests that childhood separation anxiety (CSA predisposes the subject to adult-onset panic disorder (PD. As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG. Accordingly, here we examined whether the neonatal social isolation (NSI, a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM and forced-swimming test (FST respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2 until weaning (PN21 allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26 whilst siblings (sham-isolated rats, SHAM, n = 27 and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18 remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60 and subjected to sessions of intracranial stimulation (PN65, EPM (PN66 and FST (PN67-PN68. Groups were compared by Fisher's exact test (stimulation sites, likelihood ratio chi-square tests (stimulus-response threshold curves and Bonferroni's post hoc t-tests (EPM and FST, for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate

  9. Bumetanide reduce the seizure susceptibility induced by pentylenetetrazol via inhibition of aberrant hippocampal neurogenesis in neonatal rats after hypoxia-ischemia.

    Science.gov (United States)

    Hu, Jiang-Jian; Yang, Xing-Liang; Luo, Wen-Di; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2017-04-01

    Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na + -K + -Cl - -co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Li, Xiao-Li; Jia, Tian-Ming; Luan, Bin; Liu, Tao; Yuan, Yan

    2011-04-01

    To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.

  11. Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats

    International Nuclear Information System (INIS)

    Pillet, Stephane; Rooney, Andrew A.; Bouquegneau, Jean-Marie; Cyr, Daniel G.; Fournier, Michel

    2005-01-01

    Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl 2 ) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects

  12. Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Pedro Espinosa

    2016-01-01

    Full Text Available We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL; DHT (dihydrotestosterone of 1.0 mg/50 μL; EV (estradiol valerate of 0.1 mg/50 μL; and control (sesame oil of 50 μL. At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase and cellular (tyrosine hydroxylase immunoreactivity studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

  13. Minocycline and Risperidone Prevent Microglia Activation and Rescue Behavioral Deficits Induced by Neonatal Intrahippocampal Injection of Lipopolysaccharide in Rats

    Science.gov (United States)

    Ding, Yu-qiang; Liu, Yong; Zhang, Xianghui; Wu, Renrong; Guo, Xiaofeng; Zhao, Jingping

    2014-01-01

    Background Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia. Methods Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (P7), and they were separately given saline, risperidone (0.5 mg/kg), minocycline (40 mg/kg) or a combination of both of them at P42 for consecutive 14 days. Behavioral changes (locomotion activity, social interaction, novel object recognition and prepulse inhibition) were examined and the number of microglia was assessed by using immunohistochemistry in adulthood. Results The adult rats in LPS-injected group showed obvious behavioral alteration (e. g. deficits in social interaction, novel object recognition and prepulse inhibition) and a dramatic increase of number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, application of either minocycline, risperidone or both of them significantly rescued behavioral deficits and attenuated microglia activation. Conclusion Our results suggest that inhibition of microglia activation may be one of mechanisms underlying the antipsychotic effect of minocycline and risperidone. PMID:24705495

  14. Effects of Neonatal Treatment With 6-Hydroxydopamine and Endocrine Disruptors on Motor Activity and Gene Expression in Rats

    Science.gov (United States)

    Masuo, Yoshinori; Ishido, Masami; Morita, Masatoshi; Oka, Syuichi

    2004-01-01

    To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 μg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6- hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive. PMID:15303306

  15. DEXA analysis on the bones of rats exposed in utero and neonatally to static and 50 Hz electric fields.

    Science.gov (United States)

    Okudan, Berna; Keskin, Ali Umit; Aydin, Mustafa Asim; Cesur, Gökhan; Cömlekçi, Selçuk; Süslü, Harun

    2006-10-01

    Effects of the electromagnetic fields on living bodies, bones in particular, are among the relevant issues of contemporary life. In this study, we report the influences of 50 Hz and 0 Hz (static) electric fields (EF), on intact rat bones, as evaluated by dual energy X-ray absorbtion (DEXA) measurements on bone content and density when these animals (n = 27) are continuously exposed in utero and neonatally to EFs (10 kV/m) 14 days before and 14 days after their birth, for 28 days in total. Differences between 50 Hz EF and static EF groups are found to be significant (95% confidence level) for total bone mineral content (BMC), TBMC (P = .002). Differences between 50 Hz and control groups are found to be significant for total bone mineral density (BMD), TBMD (P = .002), lumbar BMC, LBMC (P = .023), and TBMC (P = .001). Differences between static EF and control groups are found to be significant for femoral BMD, FBMD (P = .009), TBMD (P = .002), LBMC (P = .001), and TBMC (P = .001). Note that TBMC parameters are jointly significant for all differences between the three groups of test animals. These results have shown that both static and 50 Hz EFs influence the early development of rat bones. However, the influence of static EFs is more pronounced than that of the 50 Hz field.

  16. Learning and memory effects of neonatal methamphetamine exposure in rats: Role of reactive oxygen species and age at assessment.

    Science.gov (United States)

    Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

    2017-11-01

    In utero methamphetamine (MA) exposure leads to a range of adverse effects, such as decreased attention, reduced working-memory capability, behavioral dysregulation, and spatial memory impairments in exposed children. In the current experiment, preweaning Sprague-Dawley rats-as a model of third trimester human exposure-were administered the spin trapping agent, N-tert-butyl-α-phenylnitrone (PBN), daily prior to MA. Rats were given 0 (SAL) or 40 mg/kg PBN prior to each MA dose (10 mg/kg, 4× per day) from postnatal day (P) 6-15. Littermates underwent Cincinnati water maze, Morris water maze, and radial water maze assessment beginning on P30 (males) or P60 (females). Males were also tested for conditioned contextual and cued freezing, while females were trained in passive avoidance. Findings show that, regardless of age/sex, neonatal MA induced deficits in all tests, except passive avoidance. PBN did not ameliorate these effects, but had a few minor effects. Taken together, MA induced learning deficits emerge early and persist, but the mechanism remains unknown. © 2017 Wiley Periodicals, Inc.

  17. Impact of Inhaled Nitric Oxide on the Sulfatide Profile of Neonatal Rat Brain Studied by TOF-SIMS Imaging

    Directory of Open Access Journals (Sweden)

    Hanane Kadar

    2014-03-01

    Full Text Available Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in preclinical models is inhaled nitric oxide (iNO. We have assessed the effect of this therapy on brain lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using a time-of-flight secondary ion mass spectrometry (TOF-SIMS method. This technique was used to map the variations in lipid composition of the rat brain and, particularly, of the white matter. Triplicate analysis showed a significant increase of sulfatides (25%–50% in the white matter on Day 10 of life in iNO-exposed animals from Day 0–7 of life. These robust, repeatable and semi-quantitative data demonstrate a potent effect of iNO at the molecular level.

  18. Bilateral bifid mandibular canal

    OpenAIRE

    Sheikhi, Mahnaz; Badrian, Hamid; Ghorbanizadeh, Sajad

    2012-01-01

    One of the normal interesting variations that we may encounter in the mandible is bifid mandibular canal. This condition can lead to difficulties when performing mandibular anesthesia or during extraction of lower third molar, placement of implants, and surgery in the mandible. Therefore diagnosis of this variation is sometimes very important and necessary.

  19. Bilateral bifid mandibular canal

    Directory of Open Access Journals (Sweden)

    Mahnaz Sheikhi

    2012-01-01

    Full Text Available One of the normal interesting variations that we may encounter in the mandible is bifid mandibular canal. This condition can lead to difficulties when performing mandibular anesthesia or during extraction of lower third molar, placement of implants, and surgery in the mandible. Therefore diagnosis of this variation is sometimes very important and necessary.

  20. Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxic-ischemic brain damage.

    Science.gov (United States)

    Dai, Chunfang; Liu, Yannan; Dong, Zhifang

    2017-11-14

    Neonatal hypoxia-ischemia is one of the main reasons that cause neuronal damage and neonatal death. Several studies have shown that tanshinone I (TsI), one of the major ingredients of Danshen, exerts potential neuroprotective effect in adult mice exposed to permanent left cerebral ischemia. However, it is unclear whether administration of TsI has neuroprotective effect on neonatal hypoxic-ischemic brain damage (HIBD), and if so, the potential mechanisms also remain unclear. Here, we reported that treatment with TsI (5 mg/kg, i.p.) significantly alleviated the deficits of myodynamia and motor functions as well as the spatial learning and memory in the rat model of HIBD. These behavioral changes were accompanied by a significant decrease in the number of neuronal loss in the CA1 area of hippocampus. Moreover, ELISA assay showed that TsI significantly increased the production of antioxidants including total antioxidant capacity (T-AOC), glutathione (GSH), total superoxide dismutase (T-SOD) and catalase (CAT), and reduced the production of pro-oxidants including hydrogen peroxide (H 2 O 2 ), total nitric oxide synthase (T-NOS) and inducible nitric oxide synthase (iNOS). Taken together, these results indicate that TsI presents potential neuroprotection against neuronal damage via exerting significantly antioxidative activity and against pro-oxidant challenge, thereby ameliorating hypoxia-ischemia-induced motor and cognitive impairments in the neonatal rats, suggesting that TsI may be a potential therapeutic agent against HIBD.

  1. Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats

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    Hyunha Kim

    2018-01-01

    Full Text Available Aim. Neonatal hypoxic-ischemia (HI due to insufficient oxygen supply and blood flow during the prenatal and postnatal periods can cause cerebral palsy, a serious developmental condition. The purpose of this study was to investigate the efficacy of combining constraint-induced movement therapy (CIMT and electroacupuncture to treat rat neonatal HI brain injury. Methods. The left common carotid arteries of postnatal day 7 rats were ligated to induce HI brain injury, and the neonates were kept in a hypoxia chamber containing 8% oxygen for 2 hrs. Electroacupuncture at Baihui (GV 20 and Zusanli (ST 36 was performed concurrently with CIMT 3 weeks after HI induction for 4 weeks. Results. Motor asymmetry after HI was significantly improved in the CIMT and electroacupuncture combination group, but HI lesion size was not improved. The combination of CIMT and electroacupuncture after HI injury increases NeuN and decreases GFAP levels in the cerebral cortex, suggesting that this combination treatment inversely regulates neurons and astrocytes. In addition, the combination treatment group reduced the level of cleaved caspase-3, a crucial mediator of apoptosis, in the cortex. Conclusions. Our findings indicate that a combination of CIMT and electroacupuncture is an effective method to treat hemiplegia due to neonatal HI brain injury.

  2. Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

    Science.gov (United States)

    Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

    2014-10-01

    Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study

    OpenAIRE

    Arambula, Sheryl E.; Belcher, Scott M.; Planchart, Antonio; Turner, Stephen D.; Patisaul, Heather B.

    2016-01-01

    Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the no-observed-adverse-effect level can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain in...

  4. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report

    OpenAIRE

    Alexandre-Gouabau, Marie Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair; WINER, Norbert; Darmaun, Dominique

    2017-01-01

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulli...

  5. Changes in the endocrine system which controls reproduction in female rats neonatally exposed to a low-dose of gamma irradiation

    International Nuclear Information System (INIS)

    Freud, A.

    1988-06-01

    Exposure of animals to high doses of ionizing radiation causes irreversible damage to the reproductive system and brings upon infertility. The results of this work indicate that neonatal exposure of female rats on day 8 of life to gamma irradiation of 6 R and 15 R causes reduction in number of offspring these rats produce when mature. The latter results from hormonal changes in the endocrine system which controls reproduction. However, one could not define one site of the hypothalamo - hypophyseal - ovarian axis which when damaged would be responsible for the radiation-induced damage to the productive system. (Author)

  6. Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

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    Mahmoud Hosseini

    2010-01-01

    Full Text Available INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01. In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001, and the time spent by this group in the target quadrant (Q1 during the probe trial was significantly lower (P<0.001. There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05. CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s remains to be elucidated.

  7. The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in Neonatal Rat Ventricular Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Ruwani P Hewawasam

    Full Text Available The cardiac ryanodine receptor (RyR2 is an intracellular ion channel that regulates Ca2+ release from the sarcoplasmic reticulum (SR during excitation-contraction coupling in the heart. The glutathione transferases (GSTs are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with therapeutic implications. The C-terminal half of GSTM2 (GSTM2C is essential for RyR2 inhibition, and mutations F157A and Y160A within GSTM2C prevent the inhibitory action. Our objective in this investigation was to determine whether GSTM2C can enter cultured rat neonatal ventricular cardiomyocytes and influence contractility. We show that oregon green-tagged GSTM2C (at 1 μM is internalized into the myocytes and it reduces spontaneous contraction frequency and myocyte shortening. Field stimulation of myocytes evoked contraction in the same percentage of myocytes treated either with media alone or media plus 15 μM GSTM2C. Myocyte shortening during contraction was significantly reduced by exposure to 15 μM GSTM2C, but not 5 and 10 μM GSTM2C and was unaffected by exposure to 15 μM of the mutants Y160A or F157A. The amplitude of the Ca2+ transient in the 15 μM GSTM2C - treated myocytes was significantly decreased, the rise time was significantly longer and the decay time was significantly shorter than in control myocytes. The Ca2+ transient was not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C entering the myocytes and inhibiting RyR2, in a manner that indicates a possible therapeutic potential for treatment of arrhythmia in the neonatal heart.

  8. Altered astrocyte-neuronal interactions after hypoxia-ischemia in the neonatal brain in female and male rats.

    Science.gov (United States)

    Morken, Tora Sund; Brekke, Eva; Håberg, Asta; Widerøe, Marius; Brubakk, Ann-Mari; Sonnewald, Ursula

    2014-09-01

    Increased susceptibility to excitotoxicity of the neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of astrocytes for glutamate uptake, and mitochondrial failure probably plays a key role in the delayed injury cascade. Male infants have poorer outcome than females after HI, possibly linked to differential intermediary metabolism. [1-(13)C]glucose and [1,2-(13)C]acetate were injected at zero, 6, and 48 hours after unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with magnetic resonance spectroscopy. Mitochondrial metabolism was generally reduced in the ipsilateral hemisphere for ≤6 hours after HI, whereas contralaterally, it was reduced in neurons but not in astrocytes. Transfer of glutamate from neurons to astrocytes was increased in the contralateral, but not in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after HI. The transfer of glutamine from astrocytes to glutamatergic neurons was unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was decreased, whereas partial pyruvate recycling (astrocytes) was increased directly after HI. Male pups had lower astrocytic mitochondrial metabolism than females immediately after HI, whereas that of females was reduced longer and encompassed both neurons and astrocytes. The prolonged depression in mitochondrial metabolism indicates that mitochondria are vulnerable targets in the delayed injury after neonatal HI. The degree of astrocytic malfunction may be a valid indicator of outcome after hypoxic/HI brain injury and may be linked to the differential outcome in males and females. © 2014 American Heart Association, Inc.

  9. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

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    Karen Schellong

    Full Text Available BACKGROUND: Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. METHODS AND FINDINGS: By rearing in normal (NL vs. small litters (SL, small-for-gestational-age (SGA rats were neonatally exposed to either normal (SGA-in-NL or over-feeding (SGA-in-SL, and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL. SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60, as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05, and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05. Lasercapture microdissection (LMD-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc in SGA-in-SL rats (p<0.05. Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy, agouti-related-peptide (Agrp and galanin (Gal was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01, correlated to food intake (p<0.05. CONCLUSION: Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding

  10. [Reduction in hypoxia-derived neuroinflammation and dysfunctional glutamate transporters by minocycline may restore hypoxia-injured cognition of neonatal rat].

    Science.gov (United States)

    Li, Hong-Chun; Xiao, Jie; Huang, Yi-Long; Li, Long-Jun; Jiang, Hong; Huang, Li-Xuan; Yang, Ting; Yang, Ling; Li, Fan

    2016-04-25

    The aim of the present study was to investigate the effects of minocycline on cognitive functions in neonatal rat after hypoxia exposure and the underlying mechanism. A model of hypoxic brain damage (HBD) was developed by exposing postnatal 1 day (P1) rats to systemic hypoxia. The rats were intraperitoneally injected with normal saline (Hy group) or minocycline (Hy + M group) 2 h after hypoxia exposure. Some other P1 rats that were not subjected to systemic hypoxia were used as normal control (NG group). The Y-maze test was used to evaluate learning and memory ability on postnatal day 30. Inflammatory mediators (Iba-1, IL-1β, TNF-α and TGF-β1), glutamate transporters (EAAT1 and EAAT2), total Tau and phosphorylated Tau (phosphorylation sites: Tyr18, Thr205, Thr231, Ser396 and Ser404) protein expressions in the hippocampus were detected by Western blot 7 d after hypoxic exposure. The results showed that hypoxia induced learning and memory impairments of the neonatal rats, and minocycline administration could reverse the effects of hypoxia. The protein expression levels of Iba-1, IL-1β, TNF-α, EAAT2 and Tau phosphorylated at T231 were increased, but the total Tau expression was decreased in the hippocampus of the rats from Hy group 7 d after hypoxia exposure. In the hypoxia-treated rats, minocycline down-regulated Iba-1, IL-1β, TNF-α and EAAT2 protein expressions significantly, but did not affect total Tau and phosphorylated Tau protein expressions. Our results suggest that minocycline can prevent cognitive deficits of rats with hypoxia exposure, and the underlying mechanism may involve the inhibition of neuroinflammation and dysfunctional glutamate transporters but not the regulation of the Tau hyperphosphorylation.

  11. Intermittent hypoxia-induced respiratory long-term facilitation is dominated by enhanced burst frequency, not amplitude, in spontaneously breathing urethane-anesthetized neonatal rats.

    Science.gov (United States)

    Reid, Inefta M; Solomon, Irene C

    2014-01-01

    Acute intermittent hypoxia (AIH) triggers a form of respiratory plasticity known as long-term facilitation (LTF), which is manifested as a progressive increase in respiratory motor activity that lasts for minutes to hours after the hypoxic stimulus is removed. Respiratory LTF has been reported in numerous animal models, but it appears to be influenced by a variety of factors (e.g., species, age, and gender). While most studies focusing on respiratory LTF have been conducted in adult (including young adult) rat preparations, little is known about the influence of postnatal maturation on AIH-induced respiratory LTF. To begin to address this issue, we examined diaphragm EMG activity in response to and at 5-min intervals for 60 min following three 5-min episodes of hypoxia (8% O2) in urethane-anesthetized spontaneously breathing P14-P15 neonatal rats (n=15). For these experiments, the hypoxic episodes were separated by hyperoxia (40% O2), and all rats were continuously supplied with ~4% CO2. During the AIH trials, burst frequency was increased by ~20-90% above baseline in each of the rats examined while changes in burst amplitude were highly variable. Following the AIH episodes, respiratory LTF was characterized by predominantly an increase in burst frequency (fLTF) ranging from ~10% to 55%, with most rats exhibiting a 20-40% increase. In seven rats, however, an increase in amplitude (ampLTF) (~10%, n=3; ~20%, n=3; ~30%, n=1) was also noted. These data suggest that in contrast to observations in anesthetized ventilated adult rats, in anesthetized spontaneously breathing P14-P15 neonatal rats, respiratory LTF is dominated by fLTF, not ampLTF. © 2014 Elsevier B.V. All rights reserved.

  12. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats.

    Science.gov (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg -1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups.

  13. Modulation of pancreatic β-cells in neonatally streptozotocin-induced type 2 diabetic rats by the ethanolic extract of Momordica charantia fruit pulp.

    Science.gov (United States)

    Hafizur, Rahman Md; Kabir, Nurul; Chishti, Sidra

    2011-02-01

    Effective doses of the Momordica charantia fruit pulp (MCF) ethanolic extract on pancreatic β-cells modulation in neonatally streptozotocin-induced type 2 diabetic rats were studied. Diabetic rats (n=8) were treated with MCF extract (400 mg kg(-1) day(-1)) or glibenclamide (5 mg kg(-1)) for 28 days. Control rats (n=11) and untreated diabetic rats (n=8) received only water. Fasting glucose, serum insulin (by ELISA) and β-cell function (HOMA %B by homeostasis model assessment) were measured. β- and α-cells were identified by immunostaining, nuclei by DAPI, and β-cell size and number by morphometry. Significant improvement of fasting blood glucose, serum insulin and β-cell function was observed with the MCF extract for the diabetic rat model. The islet size, total β-cell area and number of β-cells were increased to almost double in the diabetic rats treated with MCF extract as compared to the untreated diabetic rats. The number of α-cells did not change significantly. Insulin granules in β-cells were notably reduced in diabetic islets as compared to control islets. However, extract-treated diabetic rat β-cells were abundant with insulin granules, which was comparable to non-diabetic control islets. The modulation of pancreatic β-cells may be involved in the experimental observation of anti-diabetic effects of M. charantia extract.

  14. Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

    Science.gov (United States)

    Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

    2016-01-01

    Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Desnutrição neonatal e microbiota normal da cavidade oral em ratos Neonatal malnutrition and normal microbiota of the oral cavity in rats

    Directory of Open Access Journals (Sweden)

    Solange Maria Magalhães da Silva Porto

    2007-12-01

    Full Text Available OBJETIVO: Avaliar a influência da desnutrição neonatal sobre o padrão e o crescimento de bactérias aeróbias, da microbiota normal da cavidade oral, em ratos Wistar adultos. MÉTODOS: O material da cavidade oral foi coletado através de swabs embebidos em 40µL de solução salina estéril e colocados em tubos estéreis contendo 960µL de brain heart infusion. Posteriormente, fez-se homogeneização de cada uma amostra. Então, destes 1.000µL, retirou-se 1µL e este foi semeado em placas de Petri contendo Agar-sangue e Levine para isolamento e identificação de bactérias Gram+ e Gram-, respectivamente. Essas placas foram incubadas em estufa bacteriológica a 37ºC, 48 horas, e as unidades formadoras de colônias que cresceram foram contadas e seus percentuais calculados. Para a bacterioscopia foram confeccionadas lâminas coradas pelo método de Gram. RESULTADOS: Do 5º ao 21º dia de vida os pesos corporais do grupo desnutrido (33,6g:42,8g, desvio-padrão=27,2g foram menores (pOBJECTIVE: To evaluate the influence of neonatal malnutrition on the pattern and growth of aerobic bacteria of the normal bacterial flora of the oral cavity in adults Wistar rats. METHODS: In the present study, the material of the oral cavity was collected through swabs soaked in 40µL of sterile saline solution. After the collection, each swab was placed in a sterile tube containing 960µL of brain heart infusion. Later, the samples were homogenized. Then, from the 1.000µL, 1µL was collected with a gauged loop to be sowed in Petri dishes containing Agar-blood and Agar-Levine, for the isolation and identification of the Gram-positive and Gram-negative bacteria respectively. The plates were placed into a bacteriological incubator, 37ºC, for 48 hours and the colony-forming units that grew were counted and their percentages were calculated. For bacterioscopy, slides were stained with the Gram method. RESULTS: From the 5th to the 21st day of life, body weight of

  16. Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords

    Directory of Open Access Journals (Sweden)

    Chun-Kuei Su

    2018-03-01

    Full Text Available Nitric oxide (NO is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM. NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors, indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker, gabazine (a GABAA receptor blocker, or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor

  17. Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords.

    Science.gov (United States)

    Su, Chun-Kuei; Chen, Yi-Yin; Ho, Chiu-Ming

    2018-01-01

    Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM). NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors), indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker), gabazine (a GABA A receptor blocker), or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker) also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor) pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor activities were found

  18. KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment.

    Science.gov (United States)

    Hernandez-Ojeda, Mariana; Ureña-Guerrero, Monica E; Gutierrez-Barajas, Paola E; Cardenas-Castillo, Jazmin A; Camins, Antoni; Beas-Zarate, Carlos

    2017-05-09

    Neonatal monosodium glutamate (MSG) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. Na + /Ca 2+ exchangers (NCX1-3) are implicated in Ca 2+ brain homeostasis; normally, they extrude Ca 2+ to control cell inflammation, but after damage and in epilepsy, they introduce Ca 2+ by acting in the reverse mode, amplifying the damage. Changes in NCX3 expression in the hippocampus have been reported immediately after neonatal MSG treatment. In this study, the expression level of NCX1-3 in the entorhinal cortex (EC) and hippocampus (Hp); and the effects of blockade of NCXs on the seizures induced by 4-Aminopyridine (4-AP) were analysed in adult rats after neonatal MSG treatment. KB-R7943 was applied as NCXs blocker, but is more selective to NCX3 in reverse mode. Neonatal MSG treatment was applied to newborn male rats at postnatal days (PD) 1, 3, 5, and 7 (4 g/kg of body weight, s.c.). Western blot analysis was performed on total protein extracts from the EC and Hp to estimate the expression level of NCX1-3 proteins in relative way to the expression of β-actin, as constitutive protein. Electrographic activity of the EC and Hp were acquired before and after intracerebroventricular (i.c.v.) infusion of 4-AP (3 nmol) and KB-R7943 (62.5 pmol), alone or in combination. All experiments were performed at PD60. Behavioural alterations were also recorder. Neonatal MSG treatment significantly increased the expression of NCX3 protein in both studied regions, and NCX1 protein only in the EC. The 4-AP-induced epileptiform activity was significantly higher in MSG-treated rats than in controls, and KB-R7943 co-administered with 4-AP reduced the epileptiform activity in more prominent way in MSG-treated rats than in controls. The long-term effects of neonatal MSG treatment include increases on functional expression of NCXs (mainly of NCX3) in the EC and Hp, which seems to contribute to

  19. Milk-borne epidermal growth factor modulates bilirubin levels in neonatal rats

    Directory of Open Access Journals (Sweden)

    Didem Cemile Yesilirmak

    2015-11-01

    Conclusion: Results suggest that EGF supplementation in newborn rats leads to a significant increase in intestinal mucosal proliferation and a significant decrease in bilirubin elimination. These data suggest that EGF possibly increases intestinal bilirubin absorption and may have a role in development of breast milk jaundice. Further studies are needed to confirm this hypothesis.

  20. Pancreatic islet insulin secretion and metabolism in adult rats malnourished during neonatal life

    DEFF Research Database (Denmark)

    Barbosa, Francisco B; Capito, Kirsten; Kofod, Hans

    2002-01-01

    Pancreatic islets were isolated from rats that had been nursed by dams fed with a control or an 8.7% protein diet during the first 12 d of the lactation period. Glucose-induced insulin secretion from islets in the 8.7% protein group was reduced 50%. The islet insulin and DNA content were similar...

  1. Behavioural characterisation of rats exposed neonatally to bisphenol-A: responses to a novel environment and to methylphenidate challenge in a putative model of attention-deficit hyperactivity disorder.

    NARCIS (Netherlands)

    Kiguchi, M.; Fujita, S.; Oki, H.; Shimizu, N.; Cools, A.R.; Koshikawa, N.

    2008-01-01

    Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder (ADHD), because such rats exhibit motor hyperactivity. To strengthen the face validity of this animal model, the present study

  2. Contribution of mineralocorticoid and glucocorticoid receptors to the chronotropic and hypertrophic actions of aldosterone in neonatal rat ventricular myocytes.

    Science.gov (United States)

    Rossier, Michel F; Python, Magaly; Maturana, Andrés D

    2010-06-01

    Mineralocorticoids and glucocorticoids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy. We previously observed, using isolated neonate rat ventricular cardiomyocytes, that both aldosterone (Aldo) and corticosterone induced in vitro a marked acceleration of the spontaneous contractions of these cells, a phenomenon dependent on the expression of the low threshold T-type calcium channels. Because both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mediated the chronotropic response to corticosteroids, we characterized the role of each receptor using spironolactone and mifepristone (RU-486) as specific antagonists. We first observed that GR antagonism, but not MR antagonism, completely disrupted the significant correlation existing between the level of T channel mRNA and the beating frequency; this difference could not be explained by a specific regulation of channel expression or activity by one of the receptors. Moreover, the chronotropic action of Aldo was additive to that of forskolin, a direct activator of the cAMP pathway. This additive response was selectively abolished upon GR inhibition. Finally, myocyte hypertrophy induced in vitro by Aldo was completely prevented by GR antagonism, whereas spironolactone had only a marginal effect. These results suggest that, in isolated rat ventricular cardiomyocytes, the activation of both MR and GR is necessary for a complete electrical remodeling and a maximal chronotropic response to corticosteroids. However, GR alone appears involved in the sensitization of the cells to the chronotropic regulation through the cAMP pathway and in the hypertrophic response to steroids. These observations have therapeutic implications given the fact that MR becomes a major target of pharmacological drugs in the clinical practice for preventing cardiac function decompensation and evolution toward heart failure and lethal arrhythmias.

  3. Despite Differences in Cytosolic Calcium Regulation, Lidocaine Toxicity Is Similar in Adult and Neonatal Rat Dorsal Root Ganglia in Vitro

    Science.gov (United States)

    Doan, Lisa V.; Eydlin, Olga; Piskoun, Boris; Kline, Richard P; Recio-Pinto, Esperanza; Rosenberg, Andrew D; Blanck, Thomas JJ; Xu, Fang

    2013-01-01

    Background Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action for local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, we examined whether there were differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. Methods DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. Results The mean KCl-induced calcium transient was greater in P7 neurons (p lidocaine significantly inhibited KCl-induced calcium responses in both ages (p lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Conclusions Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses. PMID:23851347

  4. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

    Science.gov (United States)

    Rentea, Rebecca M; Liedel, Jennifer L; Fredrich, Katherine; Welak, Scott R; Pritchard, Kirkwood A; Oldham, Keith T; Simpson, Pippa M; Gourlay, David M

    2012-10-01

    Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Intestinal ischemia-reperfusion induced diaphragm contractility dysfunction: Electrophysiological and ultrastructural study in a neonatal rat model.

    Science.gov (United States)

    Taşkınlar, Hakan; Naycı, Ali; Çömelekoğlu, Ülkü; Polat, Gürbüz; Zorludemir, Suzan; Avlan, Dinçer

    2016-03-01

    To evaluate the remote effect of intestinal ischemia reperfusion (IR) injury mediated by tumor necrosis factor alpha (TNF-α) on diaphragm contractility functions and whether administration of NAC may counteract the possible detrimental effects in an experimental neonatal rat model. 40 Wistar rat pups were randomized into four groups; ten animals in each. Intestinal ischemia was conducted by obstructing mesentery of intestines by a silk loop. In the control group; only laparotomy was performed. After 1h ischemia, reperfusion was conducted for 1h in 1h group, 24h for 24h group and 24h for 24h+NAC group but administration of NAC (150mg/kg/day) intraperitoneally twice a day was performed. Inflammatory response was evaluated by tissue TNF-α level and contractility functions by mechanic activity studies of the diaphragm. Electrophysiology of the diaphragm and the phrenic nerve was conducted to determine neuropathy or myopathy and transmission electron microscopy was performed to evaluate ultrastructural changes in the phrenic nerve. Diaphragm tissue TNF-α level significantly increased in 1h and 24h groups (P=0.004, P=0.0001; respectively). Diaphragm mechanic activation force and duration significantly decreased at 1h and 24h (P=0.004, P=0.02 and P=0.0001, P=0.0001; respectively). NAC administration significantly prevented decrease in the maximal contraction and the duration (PIntestinal IR induced elevation of TNF-α level in the diaphragm. Impairment in the diaphragm contractility and neuropathic changes in the phrenic nerve occurred even in the first hour of reperfusion. NAC administration prevented these detrimental effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats.

    Science.gov (United States)

    Rosa, Suzan G; Quines, Caroline B; da Rocha, Juliana T; Bortolatto, Cristiani F; Duarte, Thiago; Nogueira, Cristina W

    2015-07-05

    Monosodium glutamate (MSG) is a neuroexcitatory amino acid commonly used as flavoring of foods. MSG neonatal administration to animals leads to behavioral and physiological disorders in adulthood, including increased pain sensitivity. This study aimed to investigate the effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, on nociception induced by MSG. Newborn Wistar rats received 10 subcutaneous injections of MSG at a dose of 4.0g/kg or saline (once daily). At the 60th day of life, the rats were daily treated with (PhSe)2 (1mg/kg) or vehicle (canola oil) by the intragastric route for 7 days. The behavioral tests (locomotor activity, hot plate, tail-immersion and mechanical allodynia) were carried out. Ex vivo assays were performed in samples of hippocampus to determine Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, cytokine levels and [(3)H]glutamate uptake. The results demonstrated that MSG increased nociception in the hot plate test and in the mechanical allodynia stimulated by Von-Frey hair but did not alter the tail immersion test. (PhSe)2 reversed all nociceptive behaviors altered by MSG. MSG caused an increase in Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and in pro-inflammatory cytokine levels and a decrease in the anti-inflammatory cytokine and in the [(3)H]glutamate uptake. (PhSe)2 was effective in reversing all alterations caused by MSG. The results indicate that (PhSe)2 had a potential antinociceptive and anti-inflammatory action in the MSG model. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Ruemmler, P.S.; Ryan, J.L.

    1984-01-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235 Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237 Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235 Np and either ferric or ferrous iron. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V)

  8. Horizontal Synchronization of Neuronal Activity in the Barrel Cortex of the Neonatal Rat by Spindle-Burst Oscillations

    Science.gov (United States)

    Suchkov, Dmitrii; Sharipzyanova, Lyaila; Minlebaev, Marat

    2018-01-01

    During development, activity in the somatosensory cortex is characterized by intermittent oscillatory bursts at gamma (early gamma-oscillations, EGOs) and alpha–beta (spindle-bursts, SBs) frequencies. Here, we explored the topography of EGOs and SBs in the neighbor barrels of the whisker-related barrel cortex of neonatal rats (P4-7) during responses evoked by simultaneous activation of multiple whiskers as it occurs during natural conditions. We found that brief simultaneous deflection of all whiskers evoked complex neuronal responses comprised of EGOs and SBs. In contrast to EGOs, that specifically synchronized neuronal activity in each individual barrel, SBs efficiently synchronized activity between neighboring barrels. After plucking a single whisker, synchronous stimulation of spared whiskers evoked EGO-lacking responses in the whisker-deprived barrel, even though the remaining neuronal activity was synchronized by SBs in neighboring barrels. Thus, EGOs specifically support topographic synchronization of neuronal activity within barrels, whereas SBs support horizontal synchronization between neighboring barrels during stimulation of multiple whiskers. We suggest that these two co-existing activity patterns coordinate activity-dependent formation of topographic maps and support the emergence of integrative functions in the primary somatosensory cortex during the critical period of somatosensory maps development. PMID:29403359

  9. Horizontal Synchronization of Neuronal Activity in the Barrel Cortex of the Neonatal Rat by Spindle-Burst Oscillations

    Directory of Open Access Journals (Sweden)

    Dmitrii Suchkov

    2018-01-01

    Full Text Available During development, activity in the somatosensory cortex is characterized by intermittent oscillatory bursts at gamma (early gamma-oscillations, EGOs and alpha–beta (spindle-bursts, SBs frequencies. Here, we explored the topography of EGOs and SBs in the neighbor barrels of the whisker-related barrel cortex of neonatal rats (P4-7 during responses evoked by simultaneous activation of multiple whiskers as it occurs during natural conditions. We found that brief simultaneous deflection of all whiskers evoked complex neuronal responses comprised of EGOs and SBs. In contrast to EGOs, that specifically synchronized neuronal activity in each individual barrel, SBs efficiently synchronized activity between neighboring barrels. After plucking a single whisker, synchronous stimulation of spared whiskers evoked EGO-lacking responses in the whisker-deprived barrel, even though the remaining neuronal activity was synchronized by SBs in neighboring barrels. Thus, EGOs specifically support topographic synchronization of neuronal activity within barrels, whereas SBs support horizontal synchronization between neighboring barrels during stimulation of multiple whiskers. We suggest that these two co-existing activity patterns coordinate activity-dependent formation of topographic maps and support the emergence of integrative functions in the primary somatosensory cortex during the critical period of somatosensory maps development.

  10. High-frequency sarcomeric auto-oscillations induced by heating in living neonatal cardiomyocytes of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Shintani, Seine A.; Oyama, Kotaro [Department of Pure and Applied Physics, School of Advanced Science and Engineering, Waseda University, Tokyo (Japan); Fukuda, Norio, E-mail: noriof@jikei.ac.jp [Department of Cell Physiology, The Jikei University School of Medicine, Tokyo (Japan); Ishiwata, Shin’ichi, E-mail: ishiwata@waseda.jp [Department of Pure and Applied Physics, School of Advanced Science and Engineering, Waseda University, Tokyo (Japan); WASEDA Bioscience Research Institute in Singapore (WABIOS) (Singapore)

    2015-02-06

    Highlights: • We tested the effects of infra-red laser irradiation on cardiac sarcomere dynamics. • A rise in temperature (>∼38 °C) induced high-frequency sarcomeric auto-oscillations. • These oscillations occurred with and without blockade of intracellular Ca{sup 2+} stores. • Cardiac sarcomeres can play a role as a temperature-dependent rhythm generator. - Abstract: In the present study, we investigated the effects of infra-red laser irradiation on sarcomere dynamics in living neonatal cardiomyocytes of the rat. A rapid increase in temperature to >∼38 °C induced [Ca{sup 2+}]{sub i}-independent high-frequency (∼5–10 Hz) sarcomeric auto-oscillations (Hyperthermal Sarcomeric Oscillations; HSOs). In myocytes with the intact sarcoplasmic reticular functions, HSOs coexisted with [Ca{sup 2+}]{sub i}-dependent spontaneous beating in the same sarcomeres, with markedly varying frequencies (∼10 and ∼1 Hz for the former and latter, respectively). HSOs likewise occurred following blockade of the sarcoplasmic reticular functions, with the amplitude becoming larger and the frequency lower in a time-dependent manner. The present findings suggest that in the mammalian heart, sarcomeres spontaneously oscillate at higher frequencies than the sinus rhythm at temperatures slightly above the physiologically relevant levels.

  11. Activation of serotonergic neurons in the medullary caudal raphe shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

    Science.gov (United States)

    Donnelly, William T; Xia, Luxi; Bartlett, Donald; Leiter, J C

    2017-08-01

    What is the central question of this study? Does activation of serotonergic neurons in the caudal medullary raphe, some of which project to the nucleus of the solitary tract, shorten the laryngeal chemoreflex? What is the main finding and its importance? We found that serotonin originating from neurons in the caudal raphe acts through a 5-HT 3 receptor located in the nucleus of the solitary tract to terminate reflex apnoea. Failure or deficiency of this arousal-related process is likely to be relevant to the pathogenesis of sudden infant death syndrome. Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who have died of SIDS. We tested the hypothesis that activation of serotoninergic neurons in the caudal medullary raphe, some of which project to the nucleus of the solitary tract (NTS), would shorten the laryngeal chemoreflex (LCR). We studied anaesthetized neonatal rat pups between postnatal days 9 and 17. We injected 5-40 μl of water into the larynx to elicit the LCR and measured the duration of respiratory disruption. Microinjection of 50 nl of 100 μm AMPA into the caudal medullary raphe shortened the apnoeas (P serotonergic termination of apnoea is likely to be relevant to the pathogenesis of SIDS. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  12. Exposure of neonatal male rats to estrogen induces abnormal morphology of the penis and loss of fertility.

    Science.gov (United States)

    Goyal, H O; Braden, T D; Williams, C S; Dalvi, P; Williams, J W; Srivastava, K K

    2004-01-01

    The research objectives are to determine whether estrogen-induced infertility is associated with abnormal morphology of the penis and if morphological alterations can be reversed by testosterone (T). Male pups received diethylstilbestrol (DES) on alternate days from postnatal days 2 to 12. They received T or empty implants at 180 days, were tested for fertility at 188 days, and terminated at 200 days. While 5/7 control males sired pups, only 1/6 did in the DES group, and 0/8 in the DES plus T group. In addition to reductions in penile length and weight, the novel structural change induced by DES, and not reversed by T, was a replacement of cavernous spaces by fat cells in the penis body. Hence, T substitution for 8 days at adulthood did not reverse infertility in rats treated neonatally with DES and provided evidence that infertility probably resulted from absence of cavernous spaces and/or accumulation of fat cells in the penis body.

  13. The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure

    Directory of Open Access Journals (Sweden)

    Lamartiniere Coral A

    2007-12-01

    Full Text Available Abstract Background Phthalate esters like n-butyl benzyl phthalate (BBP are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2–20 to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days. Results Here we show that exposure to BBP increased the uterine weight/body weight ratio at 21 days and decreased the body weight at time of vaginal opening. BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic profile of the mammary gland mainly at the end of the exposure (21 days, becoming less prominent thereafter. By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals. Conclusion These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

  14. Ghrelin protected neonatal rat cardiomyocyte against hypoxia/reoxygenation injury by inhibiting apoptosis through Akt-mTOR signal.

    Science.gov (United States)

    Wang, Lifeng; Lu, Yingjie; Liu, Xian; Wang, Xiaoyun

    2017-04-01

    Reducing reperfusion period myocardial cell damage is efficient to reduce myocardial ischemia-reperfusion injury. Ghrelin can increase myocardial contractility, improve heart failure caused by myocardial infarction. This study aimed to investigate the protective effect of Ghrelin on myocardial hypoxia/reoxygenation (H/R) injury of neonatal rat cardiomyocytes (NRCMs) and to explore the mechanisms. We isolated the NRCMs, established myocardial H/R model, blocked growth hormone secretagogue receptor (GHSR) by siRNA technique, examined cell activity by MTT and LDH assay, detected apoptosis by Hoechst 33258 staining and flow cytometry and determined the expression levels of apoptosis related proteins and signaling pathway proteins by western blot. We found that Ghrelin can significantly improve cell activity and decrease apoptosis after H/R, however this effect was abolished by GHSR-siRNA. In addition, we found that Ghrelin can significantly increase the expression of Bcl-2 but inhibit the level of Bax and caspase-3. Further mechanism study found that the phosphorylation level of signaling pathway protein Akt and mTOR in Ghrelin treated group were significantly higher than that in other groups. In conclusion, Ghrelin can reduce the H/R damage on NRCMs and inhibit the apoptosis by activating Akt-mTOR signaling pathway.

  15. Transcriptional effects of E3 ligase atrogin-1/MAFbx on apoptosis, hypertrophy and inflammation in neonatal rat cardiomyocytes.

    Science.gov (United States)

    Zeng, Yong; Li, Junjie; Wang, Hong-Xia; Guo, Shu-Bin; Yang, Hui; Zeng, Xiang-Jun; Fang, Quan; Tang, Chao-Shu; Du, Jie; Li, Hui-Hua

    2013-01-01

    Atrogin-1/MAFbx is an ubiquitin E3 ligase that regulates myocardial structure and function through the ubiquitin-dependent protein modification. However, little is known about the effect of atrogin-1 activation on the gene expression changes in cardiomyocytes. Neonatal rat cardiomyocytes were infected with adenovirus atrogin-1 (Ad-atrogin-1) or GFP control (Ad-GFP) for 24 hours. The gene expression profiles were compared with microarray analysis. 314 genes were identified as differentially expressed by overexpression of atrogin-1, of which 222 were up-regulated and 92 were down-regulated. Atrogin-1 overexpression significantly modulated the expression of genes in 30 main functional categories, most genes clustered around the regulation of cell death, proliferation, inflammation, metabolism and cardiomyoctye structure and function. Moreover, overexpression of atrogin-1 significantly inhibited cardiomyocyte survival, hypertrophy and inflammation under basal condition or in response to lipopolysaccharide (LPS). In contrast, knockdown of atrogin-1 by siRNA had opposite effects. The mechanisms underlying these effects were associated with inhibition of MAPK (ERK1/2, JNK1/2 and p38) and NF-κB signaling pathways. In conclusion, the present microarray analysis reveals previously unappreciated atrogin-1 regulation of genes that could contribute to the effects of atrogin-1 on cardiomyocyte survival, hypertrophy and inflammation in response to endotoxin, and may provide novel insight into how atrogin-1 modulates the programming of cardiac muscle gene expression.

  16. Serotonin 2A receptor mRNA levels in the neonatal dopamine-depleted rat striatum remain upregulated following suppression of serotonin hyperinnervation.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-08-05

    Sixty days after bilateral dopamine (DA) depletion (>98%) with 6-hydroxydopamine (6-OHDA) in neonatal rats, serotonin (5-HT) content doubled and 5-HT(2A) receptor mRNA expression rose 54% within the rostral striatum. To determine if striatal 5-HT(2A) receptor mRNA upregulation is dependent on increased 5-HT levels following DA depletion, neonatal rats received dual injections of 6-OHDA and 5,7-dihydroxytryptamine (5,7-DHT) which suppressed 5-HT content by approximately 90%. In these 6-OHDA/5,7-DHT-treated rats, striatal 5-HT(2A) receptor mRNA expression was still elevated (87% above vehicle controls). Comparative analysis of 5-HT(2C) receptor mRNA expression yielded no significant changes in any experimental group. These results demonstrate that upregulated 5-HT(2A) receptor biosynthesis in the DA-depleted rat is not dependent on subsequent 5-HT hyperinnervation. Copyright 1999 Elsevier Science B.V.

  17. Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

    Science.gov (United States)

    Lu, Yang; Giri, P K; Lei, Shan; Zheng, Juan; Li, Weisong; Wang, Ning; Chen, Xinlin; Lu, Haixia; Zuo, Zhiyi; Liu, Yong; Zhang, Pengbo

    2017-06-03

    Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Inhaled nitric oxide improves lung structure and pulmonary hypertension in a model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats.

    Science.gov (United States)

    Tourneux, Pierre; Markham, Neil; Seedorf, Gregory; Balasubramaniam, Vivek; Abman, Steven H

    2009-12-01

    Whether inhaled nitric oxide (iNO) prevents the development of bronchopulmonary dysplasia (BPD) in premature infants is controversial. In adult rats, bleomycin (Bleo) induces lung fibrosis and pulmonary hypertension, but the effects of Bleo on the developing lung and iNO treatment on Bleo-induced neonatal lung injury are uncertain. Therefore, we sought to determine whether early and prolonged iNO therapy attenuates changes of pulmonary vascular and alveolar structure in a model of BPD induced by Bleo treatment of neonatal rats. Sprague-Dawley rat pups were treated with Bleo (1 mg/kg ip daily) or vehicle (controls) from day 2 to 10, followed by recovery from day 11 to 19. Treatment groups received early (days 2-10), late (days 11-19), or prolonged iNO therapy (10 ppm; days 2-19). We found that compared with controls, Bleo increased right ventricular hypertrophy (RVH), and pulmonary arterial wall thickness, and reduced vessel density alveolarization. In each iNO treatment group, iNO decreased RVH (P rats, and that early and prolonged iNO therapy prevents right ventricle hypertrophy and pulmonary vascular remodeling and partially improves lung structure.

  19. Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

    Directory of Open Access Journals (Sweden)

    Manhães de Castro R.

    2001-01-01

    Full Text Available Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days treated from the 1st to the 19th postnatal day with citalopram (CIT, a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days. Aggressive behavior was induced by placing a pair of rats (matched by weight in a box (20 x 20 x 20 cm, and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval. When compared to the control group (rats treated for the same period with equivalent volumes of saline solution, the CIT group presented a 41.4% reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect.

  20. Posture effects on spontaneous limb movements, alternated stepping, and the leg extension response in neonatal rats.

    Science.gov (United States)

    Mendez-Gallardo, Valerie; Roberto, Megan E; Kauer, Sierra D; Brumley, Michele R

    2016-03-01

    The development of postural control is considered an important factor for the expression of coordinated behavior such as locomotion. In the natural setting of the nest, newborn rat pups adapt their posture to perform behaviors of ecological relevance such as those related to suckling. The current study explores the role of posture in the expression of three behaviors in the newborn rat: spontaneous limb activity, locomotor-like stepping behavior, and the leg extension response (LER). One-day-old rat pups were tested in one of two postures--prone or supine--on each of these behavioral measures. Results showed that pups expressed more spontaneous activity while supine, more stepping while prone, and no differences in LER expression between the two postures. Together these findings show that posture affects the expression of newborn behavior patterns in different ways, and suggest that posture may act as a facilitator or a limiting factor in the expression of different behaviors during early development. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Efeitos de longo prazo do estresse neonatal com lipopolissacarídeo em ratos = Long-term effects of neonatal stress using lipopolysaccharide in rats

    Directory of Open Access Journals (Sweden)

    Lunardelli, Adroaldo

    2014-01-01

    Full Text Available Introdução: Diversos modelos experimentais têm sido utilizados para demonstrar que intervenções no início da vida podem gerar alterações permanentes que perduram ao longo da vida. A administração de lipopolissacarídeo (LPS no período neonatal gera um estímulo imunológico estressante capaz de alterar muitas respostas fisiológicas ao estresse na vida adulta. Objetivo: Revisar a literatura acerca das influências, em longo prazo, que a administração de LPS no período neonatal pode gerar na vida adulta em modelos experimentais. Materiais e Métodos: O presente estudo consiste em uma revisão integrativa da literatura com base na busca de artigos científicos disponíveis nas bases de dados Medline/PubMed e Science Direct, utilizando os descritores neonatal programming, neonatal stress, neonatal LPS e neonatal lipopolysaccharide. Foram incluídas publicações cuja temática abordasse os resultados da utilização de LPS como estressor neonatal em protocolos experimentais, sem limite de data. Resultados: Foram selecionados 15 artigos que mostram modelos experimentais em que a injeção de LPS em ratos neonatos causa modificações funcionais da resposta do eixo hipotálamo-hipófise-adrenal (HPA quando adultos, incluindo elevação nos níveis plasmáticos de corticosterona. Ainda, há diminuição das concentrações circulantes de citocinas pró-inflamatórias, hiperalgesia, aumento na sensibilidade ao estresse e aumento do comportamento de ansiedade e depressão. Conclusão: Os resultados demonstram que a administração neonatal de LPS consiste em um modelo experimental efetivo de programming, provocando uma série de alterações imunológicas e comportamentais na vida adulta

  2. Apoptosis in the small intestine of neonatal rat using blue light-emitting diode devices and conventional halogen-quartz devices in phototherapy.

    Science.gov (United States)

    Tanaka, Keiichiro; Hashimoto, Hisashi; Tachibana, Toshiaki; Ishikawa, Hiroshi; Ohki, Takao

    2008-07-01

    Phototherapy is the most frequently used treatment for the neonatal jaundice. However, recent papers report that phototherapy increased apoptosis in peripheral mononuclear leukocytes in vivo and in mouse lymphoma cell line in vitro. We have investigated the cytotoxicity of phototherapy on the small intestine of neonatal rat using conventional halogen-quartz device (conventional device) and blue light-emitting device (LED device) by measuring apoptotic cells. Four-day-old male Wistar rats were divided into three groups as follows: group 1, exposure to conventional device for 72 h; group 2, exposure to LED device for 72 h; and group 3, control (without phototherapy). After light exposure, the small intestine was examined for apoptosis. Apoptotic cells were detected by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, by immunohistochemistry for caspase-3 and by transmission electron microscopy. The proportion of positive cells by the TUNEL method in the epithelium of the small intestine was 6.2, 3.1 and 1.7% in the conventional device group, the LED device group and the control group, respectively. The apoptotic cells of the conventional device group is significantly higher than the LED device group (P LED device group was higher than that of the control group (P phototherapy induced apoptosis in neonatal small intestine and the conventional device introduces more apoptosis than the LED device.

  3. Regulation of pro-adrenocorticotropin-endorphin synthesis and secretion in cultured neonatal rat anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Sato, S.M.; Mains, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1987-08-01

    Previous work demonstrated that newborn rat anterior pituitary corticotropes display processing patterns for pro-ACTH/endorphin that are different from the adult. The synthesis and release of beta-endorphin-related peptides was examined in dispersed cell and explant cultures of newborn anterior pituitary to investigate corticotrope development further. The temporal pattern of pro-ACTH/endorphin processing differed significantly from adult rat melanotropes and AtT-20 cells. While pro-ACTH/endorphin processing begins within 30 min of synthesis in adult melanotropes and AtT-20 cells, pulse-labeling of newborn corticotropes in culture indicated that pro-ACTH/endorphin remained uncleaved for at least 90 min after synthesis. With further incubation, there was a decrease in radioactivity associated with the precursor and an equivalent rise in the radioactivity associated with beta-endorphin and beta-lipotropin. However, unprocessed precursor still remained in the cultured newborn anterior pituitary cells after a 25-h chase. Although intact pro-ACTH/endorphin from newborn corticotropes was very long-lived, the precursor did undergo oligosaccharide maturation and became endoglycosidase H resistant within 1 h after synthesis. Similar to the adult, pro-ACTH/endorphin synthesis was doubled in cultures of newborn anterior pituitary chronically treated with 10 nM CRF resulting in a 3- to 4-fold stimulation of secretion over the basal rate. However, unlike the AtT-20 cell or adult rat corticotrope, the proteolytic processing of pro-ACTH/endorphin in the newborn corticotrope was altered by chronic secretagogue treatment; less pro-ACTH/endorphin was converted to beta-endorphin in secretagogue-treated corticotropes than in controls. Thus processing of pro-ACTH/endorphin in the corticotrope is not mature by birth and can be regulated by chronic CRF treatment.

  4. Mere odor exposure learning in the rat neonate immediately after birth and one day later

    Science.gov (United States)

    Miller, Stacie S.; Spear, Norman E.

    2011-01-01

    Rat pups are more resistant to retroactive associative interference 3 hrs after birth than 24 hours later (Cheslock, Sanders, & Spear, 2004). The present experiments tested the effect of age, retention interval and dam presence during the retention interval on odor-induced motor activity subsequent to mere odor exposure. Rats were exposed to an hour of odor immediately after birth or approximately one day later and tested after a given retention interval (3 hrs or 27 hrs [Exp 1]; 0, 30, 75, or 180 min [Exp. 2]). They spent the retention interval either in the presence or absence of a foster dam (Exp. 1 and 3). After the retention interval, pups were tested in a four-minute activity test including a two-minute baseline period and two minutes of odor exposure. Overall activity was scored during tape-playback. Odor-exposed pups were more active than non-exposed pups during reexposure to the odor during testing, but this was true only for P0 pups. In contrast, P1 pups without prior odor exposure were active during testing and behaviorally quieted in the presence of the odor they were previously exposed to. Though one day apart, newborn rats just hours old lack many of the experiences that a one day old has had including nursing, huddling, and being groomed. These experiences are associated with, among other stimuli, a barrage of olfactory cues (e.g., colostrum, saliva, dander, feces, and urine). P0 and P1 pups also differ in their proximity from the birthing experience and associated neurochemical changes. The age-related pattern of responding to odors based on previous odor exposure was discussed in relation to these and other possibilities. PMID:20411590

  5. Evaluation of melatonin and prostaglandin E1 combination on necrotizing enterocolitis model in neonatal rats.

    Science.gov (United States)

    Cekmez, Ferhat; Cetinkaya, Merih; Tayman, Cüneyt; Canpolat, Fuat Emre; Kafa, Ilker Mustafa; Uysal, Sema; Tunc, Turan; Sarıcı, S Ümit

    2013-06-10

    Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in newborn infants but up to now there is no completely effective treatment for it. In order to show that a combination of melatonin and prostaglandins may be useful to save lives, we use newborn rat as a model of necrotizing enterocolitis to test the hypothesis of using the combination therapy might have more potential effect on mucosal cytoprotection and healing. A total of 60 newborn pups from 5 time-mated Sprague-Dawley pregnant rats were divided equally into 5 groups as follows: NEC (subjected to NEC), NEC+Melatonin, NEC+Prostaglandin, NEC+Prostaglandin+Melatonin and control. These animals were fed with hyperosmolar formula 3 times daily and subjected to 100% CO2 inhalation for 10 min, +4°C cold exposure for 5 min, and 97% O2 for 5 min twice daily to induce NEC. This procedure was applied to the pups for 3 days. The macroscopic scoring, intestinal injury scoring and apoptosis index scoring were all found to be significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. Anti-oxidant enzyme activities were significantly higher, whereas lipid peroxidation was significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. This combination therapy showed cytoprotective and healing effects on mucosa in the intestinal tissue of rat pups in necrotizing enterocolitis model. Therefore, this therapy might also show benefit in preterm infants with NEC. After confirmation of this data by other clinical and experimental studies, it may be a novel therapeutic option for the prevention of NEC in preterm infants. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hallaq, H.; Leaf, A. (Harvard Medical School, Boston, MA (USA)); Sellmayer, A. (Univ. Munchen, (Germany)); Smith, T.W. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-10-01

    Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3{endash}5 days in culture medium enriched with 5 {mu}M arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3{endash}5 days with 5 {mu}M eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable {sup 86}Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 {plus minus} 29 and 757 {plus minus} 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3{endash}5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes.

  7. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

    International Nuclear Information System (INIS)

    Hallaq, H.; Leaf, A.; Sellmayer, A.; Smith, T.W.

    1990-01-01

    Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3 endash 5 days in culture medium enriched with 5 μM arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3 endash 5 days with 5 μM eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable 86 Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 ± 29 and 757 ± 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3 endash 5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes

  8. Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight

    Science.gov (United States)

    Sabelman, E. E.; Holton, E. M.; Arnaud, C. D.

    1981-01-01

    Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.

  9. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation.

    Science.gov (United States)

    Lee, Jong-Ho; Kim, Jin Young; Jahng, Jeong Won

    2014-06-01

    This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis.

  10. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Jong-Ho Lee

    2014-06-01

    Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

  11. Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults.

    Directory of Open Access Journals (Sweden)

    Liansheng Liu

    2011-05-01

    Full Text Available A disturbance of the brain-gut axis is a prominent feature in functional bowel disorders (such as irritable bowel syndrome and functional dyspepsia and psychological abnormalities are often implicated in their pathogenesis. We hypothesized that psychological morbidity in these conditions may result from gastrointestinal problems, rather than causing them.Functional dyspepsia was induced by neonatal gastric irritation in male rats. 10-day old male Sprague-Dawley rats received 0.1% iodoacetamide (IA or vehicle by oral gavage for 6 days. At 8-10 weeks of age, rats were tested with sucrose preference and forced-swimming tests to examine depression-like behavior. Elevated plus maze, open field and light-dark box tests were used to test anxiety-like behaviors. ACTH and corticosterone responses to a minor stressor, saline injection, and hypothalamic CRF expression were also measured.Behavioral tests revealed changes of anxiety- and depression-like behaviors in IA-treated, but not control rats. As compared with controls, hypothalamic and amygdaloid CRF immunoreactivity, basal levels of plasma corticosterone and stress-induced ACTH were significantly higher in IA-treated rats. Gastric sensory ablation with resiniferatoxin had no effect on behaviors but treatment with CRF type 1 receptor antagonist, antalarmin, reversed the depression-like behavior in IA-treated ratsThe present results suggest that transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors, increased expression of CRF in the hypothalamus, and an increased sensitivity of HPA axis to stress. The depression-like behavior may be mediated by the CRF1 receptor. These findings have significant implications for the pathogenesis of psychological co-morbidity in patients with functional bowel disorders.

  12. Neuronal reorganization in adult rats neonatally exposed to (±-3,4-methylenedioxymethamphetamine

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    Michael T. Williams

    2014-01-01

    Full Text Available The abuse of methylenedioxymethamphetamine (MDMA during pregnancy is of concern. MDMA treatment of rats during a period of brain growth analogous to late human gestation leads to neurochemical and behavioral changes. MDMA from postnatal day (P11–20 in rats produces reductions in serotonin and deficits in spatial and route-based navigation. In this experiment we examined the impact of MDMA from P11 to P20 (20 mg/kg twice daily, 8 h apart on neuronal architecture. Golgi impregnated sections showed significant changes. In the nucleus accumbens, the dendrites were shorter with fewer spines, whereas in the dentate gyrus the dendritic length was decreased but with more spines, and for the entorhinal cortex, reductions in basilar and apical dendritic lengths in MDMA animals compared with saline animals were seen. The data show that neuronal cytoarchitectural changes are long-lasting following developmental MDMA exposure and are in regions consistent with the learning and memory deficits observed in such animals.

  13. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  14. Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2015-01-01

    Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson's disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially...... influence the function and/or survival of the implants and may be involved in an alternative mechanism of action. However, it is unclear if hRPE cells secreted trophic factors when handled in the manner used in the clinical Phase II trial. To address these questions, we investigated two neonatal hRPE cell...... lesioned rats compared to sham (GM-only). The data suggest that trophic factors from neonatal hRPE cell implants likely did not participate in an alternative mechanism of action, which adds supports to a hypothesis that additional factors may have been necessary for the survival and/or function of h...

  15. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt

    2010-01-01

    Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic....... Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity...... delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well...

  16. Cell death by apoptosis following X-irradiation of the foetal and neonatal rat kidney

    International Nuclear Information System (INIS)

    Gobe, G.C.; Harmon, B.V.

    1988-01-01

    A light and electron microscopic study was undertaken to determine the type of cell death induced by X-irradiation in the developing kidney. Five-day-old Sprague-Dawley rats were exposed to a whole-body dose of either 2 or 5 Gy, and foetuses in the eighteenth day of development were exposed to a dose of 4 Gy. The kidneys were examined at 4, 8 and 24 h, and at 1 and 2 weeks post-irradiation. The dying cells from both control and treated kidneys showed the morphological features of apoptosis, a distinct form of cell death that has been identified in mammalian tissues under physiological as well as pathological conditions. Necrosis was not detected. Apoptosis was infrequent in control kidneys and insignificant in extent when compared with the proliferative activity of the cells of the superficial nephrons. There was a pronounced increase in apoptosis during the first day after irradiation. (author)

  17. Aromatase is abundantly expressed by neonatal rat penis but downregulated in adulthood.

    Science.gov (United States)

    Jesmin, S; Mowa, C N; Sakuma, I; Matsuda, N; Togashi, H; Yoshioka, M; Hattori, Y; Kitabatake, A

    2004-10-01

    Although synthesis of estrogen by male gonads has been well documented for over half a century, it is only recently that the role of estrogen in male reproductive events has gained appreciation. We recently reported abundant expression of estrogen receptor (ER)-alpha and -beta in different cell types of the rat penis, whose levels diminished with advancing age. The present study, which builds on data from the ER study, was designed to determine whether the penis is capable of generating its own local estrogen by examining evidence of the expression of aromatase, a microsomal enzymatic complex which irreversibly converts androgens to estrogens, using immunohistochemistry, Western blotting, in situ hybridization and real-time PCR analyses. Secondly, the effects of sex steroid hormones on penile aromatase were examined. Discrete aromatase immunoreactive cells were localized in primordial corpus cavernosum, corpus spongiosus and os penis, blood vessels and sensory corpuscle of glans penis. In situ hybridization signals corresponded with immunohistochemical findings. Western blot, enzyme immunoassay and real-time PCR analyses of rat penile samples revealed an age-dependent expression of aromatase and estrogen, with levels at week 1 almost resembling those of the ovary, but they decreased sharply by week 8, and decreased further by week 35. This expression pattern was strikingly similar to that of ER-alpha reported previously. Testosterone and diethylstilbesterol administered prenatally upregulate levels of aromatase mRNA and protein, and estrogen postnatally. Dihydrotestosterone upregulated aromatase mRNA and protein, but not estrogen. We conclude that estrogen acts via ER in a paracrine and/or autocrine manner to regulate penile events, particularly during development, and that estrogen synthesis is regulated by estrogen and androgens.

  18. Longer hypoxia-ischemia periods to neonatal rats causes motor impairments and muscular changes.

    Science.gov (United States)

    Durán-Carabali, L E; Sanches, E F; Marques, M R; Aristimunha, D; Pagnussat, A; Netto, C A

    2017-01-06

    Prematurity and hypoxia-ischemia (HI) can lead to movement disorders in infants. Considering that mild-moderate HI induced at postnatal day (PND) 3 has failed to produce motor disabilities similar to those seen in pre-term newborns, the main goal of the present study was to verify whether longer hypoxia periods would mimic motor function impairment, brain and muscle morphological alterations. Forty-nine Wistar rat pups of both sexes were randomly assigned to surgical control (CG) and HI groups. HI animals were submitted to the Levine-Rice model at PND 3, and exposed to 120 (HI-120'), 180 (HI-180') or 210 (HI-210') minutes of hypoxia (FiO 2 : 0.08). Sensorimotor function was assessed as from PND 35-45, by means of grasping strength, adhesive removal, cylinder and ladder walking tests. Histological staining was used to quantify the striatal volume and the cross-sectional area (CSA) of skeletal muscles. Cylinder and adhesive removal test evidenced that HI-180' and HI-210' groups had asymmetrical use of the forepaws when compared to controls. HI animals showed a decrease in the step placement quality and an increase in step errors when compared to CG (P⩽0.05). Reduction in striatal volume correlates with behavioral assessment, HI-180' and HI-210' groups presented lower biceps brachii and tibialis anterior CSA. These results show that rats exposed to longer hypoxic periods at PND3 have encephalic and sensorimotor impairments that mimic those observed in preterm infants. Morphological changes in muscle tissue evidence a new pathophysiological characteristic of the HI model that might be of relevance for the study of sensorimotor deficits. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Neuronal damage and changes in the expression of muscarinic acetylcholine receptor subtypes in the neonatal rat cerebral cortical upon exposure to sparteine, a quinolizidine alkaloid.

    Science.gov (United States)

    Flores-Soto, M E; Bañuelos-Pineda, J; Orozco-Suárez, S; Schliebs, R; Beas-Zárate, C

    2006-10-01

    Sparteine is a quinolizidine alkaloid (QA) produced by Lupine species that has generated much interest due to its anti-hypertensive, anti-pyretic, and anti-inflammatory properties. In the nervous system, sparteine has been shown to display anti-cholinergic and depressive activity, although how sparteine exerts its toxic effects in the brain remains unclear. We have addressed this issue by administering subcutaneous injections of sparteine (25 mg/kg of body weight) to rats on postnatal days 1 and 3, and then examining the expression of the muscarinic acetylcholine receptor (mAChR) subunits m1-m4 in the brains of the neonatal rats 14-60 days later. Administration of sparteine to neonatal rats caused neuronal damage in the cerebral motor cortex accompanied by transient changes in the expression of m1-m4 mAChR subunits as revealed by both RT-PCR and Western blotting. This effect could be prevented by pre-treatment with atropine (10 mg/kg) 1 h prior to the injection of sparteine, suggesting that the cytotoxic activity of sparteine is mediated through mAChRs.

  20. Neonatal handling decreases unconditioned anxiety, conditioned fear, and improves two-way avoidance acquisition: a study with the inbred Roman high (RHA-I- and low-avoidance (RLA-I rats of both sexes

    Directory of Open Access Journals (Sweden)

    Cristobal eRío-Alamos

    2015-07-01

    Full Text Available The present study evaluated the long-lasting effects of neonatal handling (H; administered during the first 21 days of life on unlearned and learned anxiety-related responses in inbred Roman High- (RHA-I and Low-avoidance (RLA-I rats. To this aim, untreated and neonatally-handled RHA-I and RLA-I rats of both sexes were tested in the following tests/tasks in baseline acoustic startle (BAS test, a context-conditioned fear (CCF test and the acquisition of two-way active –shuttle box- avoidance (SHAV. RLA-I rats showed higher unconditioned (NOE, ZM, BAS and conditioned (CCF, SHAV anxiety. H treatment increased exploration of the novel object in the NOE test as well as exploration of the open sections of the ZM test in both rat strains and sexes, although the effects were relatively more marked in the (high anxious RLA-I strain and in females. Neonatal handling did not affect BAS, but reduced context-conditioned fear in both strains and sexes, and improved shuttle box avoidance acquisition especially in RLA-I (and particularly in females and in female RHA-I rats. These are completely novel findings, and may suggest that H-induced changes in hippocampal function, which is enhanced in RLA-Is vs RHA-I rats, could be a candidate mechanism underlying the observed long-lasting benefits of neonatal handling on known hippocampal-dependent responses/tasks.

  1. Vitamin A Supplementation Increases the Uptake of Chylomicron Retinyl Esters into the Brain of Neonatal Rats Raised under Vitamin A-Marginal Conditions.

    Science.gov (United States)

    Hodges, Joanna K; Tan, Libo; Green, Michael H; Ross, A Catharine

    2016-09-01

    The most rapid phase of brain development occurs during the neonatal period. Vitamin A (VA; retinol) is critical for many aspects of this process, including neurogenesis, synaptic plasticity, learning, and memory formation. However, the metabolism of retinol in the neonatal brain has not been extensively explored. We examined the uptake of VA into the brain in neonatal rats raised under VA-marginal conditions (control group) and assessed the effect of VA supplementation on the uptake of VA into the brain. Sprague-Dawley neonatal rats (n = 104) nursed by mothers fed a VA-marginal diet were randomly assigned and treated on postnatal day 4 with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil as the control, both of which contained 1.8 μCi [(3)H]retinol. Pups (n = 4/group at a time) were killed at 13 sampling times from 30 min to 24 d after dosing. The uptake of total retinol, chylomicron-associated retinyl esters (REs), and retinol bound to retinol-binding protein (RBP) was estimated with the use of WinSAAM version 3.0.8. Total retinol mass in the brain was closely dependent on its mass in plasma over time (r = 0.91; P d (RBP) compared with 0.01 nmol/d (chylomicrons)]. VA supplementation increased the fractional uptake of chylomicron REs from 0.3% to 1.2% of plasma pool/d, decreased that of RBP retinol from 0.5% to 0.2% of plasma pool/d, and increased the transfer rate of chylomicron REs from nearly zero to 0.7 nmol/d, causing a day-long elevation in the brain mass of total retinol. Postprandial chylomicrons may be a primary mechanism for delivering a recently ingested large dose of VA to the brain of neonatal rats raised under VA-marginal conditions. © 2016 American Society for Nutrition.

  2. Ontogeny of gender-specific responsiveness to stress and glucocorticoids in the rat and its determination by the neonatal gonadal steroid environment.

    Science.gov (United States)

    Patchev, V K; Hayashi, S; Orikasa, C; Almeida, O F

    1999-08-01

    The neuroendocrine response to stress in the rat displays gender-specific characteristics resulting from both sex hormone-dependent organization of neuroendocrine regulatory mechanisms and the modulatory action of circulating gonadal steroids. To define the role of gonadal steroid-mediated brain differentiation in the emergence of sex-specific differences in pituitary-adrenal function, and the necessity of physiological gonadal secretions for the manifestation of these differences, we examined the ontogeny of diurnal and stress-induced corticosterone (B) secretion, and suppressibility of the latter by dexamethasone (DEX) in intact male and female rats, and in animals that were subject to neonatal manipulations of the gonadal steroid environment (orchidectomy in males and neonatal estrogenization in females). Further, gene expression of corticosteroid receptors (MR and GR), corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) under basal conditions, and following adrenalectomy (ADX) and chronic supplementation with high doses of B, were investigated in adult male and female rats, and individuals of both sexes which have been exposed to alterations of the gonadal steroid milieu during early development. The results demonstrate that: i) gender-specific differences in basal and stress-induced adrenocortical secretion are present at birth, but are still maleable by neonatal alterations of the gonadal steroid environment; ii) gender-specific dichotomy in the sensitivity of the secretory stress response to glucocorticoid feedback becomes fully manifest in adulthood; iii) sex differences in basal adrenocortical secretion become fully expressed only in the presence of intact gonads, whereas, once established by the neonatal hormonal milieu, differential sensitivity of the stress response to glucocorticoids persists in the absence of functioning gonads; iv) neonatal hormone manipulations alter sex-specific characteristics of CRH, AVP, MR and GR gene

  3. Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring.

    Directory of Open Access Journals (Sweden)

    Zoe E Clayton

    Full Text Available Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation.Pregnant rats were randomised to either control (CON or high-fructose (FR diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21 and postnatal day (P10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR.Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes.Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired

  4. Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats.

    Directory of Open Access Journals (Sweden)

    Junko Kimura-Kuroda

    Full Text Available Acetamiprid (ACE and imidacloprid (IMI belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs. Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development.Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment-including proliferation, migration, differentiation, and morphological and functional maturation-can be observed in vitro. Using these cultures, an excitatory Ca(2+-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca(2+ influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca(2+ influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine.This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian nAChRs at concentrations greater than 1 µM. Therefore, the

  5. Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

    Directory of Open Access Journals (Sweden)

    EIKI HATORI

    2006-01-01

    Full Text Available Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10mM, alpha4beta2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100mM, alpha4beta2 antagonist dihydro-beta-erythroidine (0.1-100mM, alpha7 antagonist methyllycaconitine (0.1-100mM, and a-bungarotoxin (0.01-10mM all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20mM dihydro-beta-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-beta-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that alpha4beta2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas alpha7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate

  6. Neonatal astrocyte damage is sufficient to trigger progressive striatal degeneration in a rat model of glutaric acidemia-I.

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    Silvia Olivera-Bravo

    Full Text Available BACKGROUND: We have investigated whether an acute metabolic damage to astrocytes during the neonatal period may critically disrupt subsequent brain development, leading to neurodevelopmental disorders. Astrocytes are vulnerable to glutaric acid (GA, a dicarboxylic acid that accumulates in millimolar concentrations in Glutaric Acidemia I (GA-I, an inherited neurometabolic childhood disease characterized by degeneration of striatal neurons. While GA induces astrocyte mitochondrial dysfunction, oxidative stress and subsequent increased proliferation, it is presently unknown whether such astrocytic dysfunction is sufficient to trigger striatal neuronal loss. METHODOLOGY/PRINCIPAL FINDINGS: A single intracerebroventricular dose of GA was administered to rat pups at postnatal day 0 (P0 to induce an acute, transient rise of GA levels in the central nervous system (CNS. GA administration potently elicited proliferation of astrocytes expressing S100β followed by GFAP astrocytosis and nitrotyrosine staining lasting until P45. Remarkably, GA did not induce acute neuronal loss assessed by FluoroJade C and NeuN cell count. Instead, neuronal death appeared several days after GA treatment and progressively increased until P45, suggesting a delayed onset of striatal degeneration. The axonal bundles perforating the striatum were disorganized following GA administration. In cell cultures, GA did not affect survival of either striatal astrocytes or neurons, even at high concentrations. However, astrocytes activated by a short exposure to GA caused neuronal death through the production of soluble factors. Iron porphyrin antioxidants prevented GA-induced astrocyte proliferation and striatal degeneration in vivo, as well as astrocyte-mediated neuronal loss in vitro. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that a transient metabolic insult with GA induces long lasting phenotypic changes in astrocytes that cause them to promote striatal

  7. Postsynaptic GABA(B Receptors Contribute to the Termination of Giant Depolarizing Potentials in CA3 Neonatal Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Ilgam Khalilov

    2017-06-01

    Full Text Available During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs. GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP. Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B receptor agonists. Finally, the GABA(B receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i postsynaptic GABA(B receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP.

  8. Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.

    Science.gov (United States)

    Waddell, Jaylyn; Hanscom, Marie; Shalon Edwards, N; McKenna, Mary C; McCarthy, Margaret M

    2016-01-01

    Hypoxia-ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning. Published by Elsevier Inc.

  9. Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.

    Science.gov (United States)

    Baldy, Cécile; Chamberland, Simon; Fournier, Stéphanie; Kinkead, Richard

    2017-01-01

    The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O 2 desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14-P15, pups were instrumented to monitor breathing, O 2 saturation (S p o 2 ), and heart rate. The LCR was activated by water injections near the larynx (10 µl). LCR-induced apneas were longer in stressed pups than controls; O 2 desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups.

  10. Single variant bottleneck in the early dynamics of H. influenzae bacteremia in neonatal rats questions the theory of independent action

    Science.gov (United States)

    Shao, Xinxian; Levin, Bruce; Nemenman, Ilya

    2017-08-01

    There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (Sm S and Sm R ) and otherwise isogenic strains of Haemophilus influenzae type b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, Sm S or Sm R . After ruling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that ‘shuts the door’ on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We suggest possible experiments that would be able to confirm or reject our proposed modification of the early infection model.

  11. Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

    Science.gov (United States)

    Min, Jia-Wei; Hu, Jiang-Jian; He, Miao; Sanchez, Russell M; Huang, Wen-Xian; Liu, Yu-Qiang; Bsoul, Najeeb Bassam; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2015-12-01

    Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Expression of NG2 and platelet-derived growth factor receptor alpha in the developing neonatal rat brain

    Directory of Open Access Journals (Sweden)

    Ping Li

    2017-01-01

    Full Text Available Platelet-derived growth factor receptor alpha (PDGFRα is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphology of oligodendrocyte precursor cells labeled by NG2 or PDGFRα in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive (NG2+ cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2+ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRα positive (PDGFRα+ cells were coincident with NG2+ cells. The colocalization of NG2 and PDGFRα in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRα were predominantly in the early postnatal stage of development. The numbers of NG2+/PDGFRα+ cells and PDGFRα+ cells decreased, but the number of NG2+ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRα, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRα are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.

  13. Low-level laser therapy vs. pulsed electromagnetic field on neonatal rat calvarial osteoblast-like cells.

    Science.gov (United States)

    Emes, Yusuf; Akça, Kivanç; Aybar, Buket; Yalçın, Serhat; Çavuşoğlu, Yeliz; Baysal, Uğur; Işsever, Halim; Atalay, Belir; Vural, Pervin; Ergüven, Mine; Çehreli, Murat Cavit; Bilir, Ayhan

    2013-05-01

    To compare the effects of pulsed electromagnetic field (PEMF) and low-level laser therapy (LLLT) on osteoblast cells in a cell culture model. Fifty thousand neonatal rat calvarial osteoblast-like cells per milliliter were seeded and 0.06 mT PEMF, 0.2 mT PEMF, and LLLT at 808 nm were applied for 24 and 96 h on the cells. To evaluate cellular proliferation and differentiation, specimens were examined for DNA synthesis, alkaline phosphatase (ALP) activity, cell numbers, and viability of the cells. Morphological appearances of the cells were observed using scanning electron microcopy after 24 and 96 h of incubation. At 24 and 96 h, the control group had a higher cell proliferation than 0.06 and 0.2 mT PEMF groups (p=0.001). At 96 h, 0.2 mT PEMF group had higher cell proliferation rate than 0.06 mT PEMF and LLLT groups (p=0.001). The cell count and cell viability in 0.2 mT PEMF group were higher than the 0.06-mT PEMF and LLLT groups, although these differences were not statistically significant at 96 h (p>0.05). At 24 and 96 h, cell viability in the control group was higher than the test groups. Alkaline phosphatase levels of the groups were comparable in both time intervals (p>0.05). 0.2 mT PEMF application on osteoblast-like cells led to cell proliferation and differentiation better than 0.06 mT PEMF and LLLT at 808 nm, although a remarkable effect of both PEMF and LLLT could not be detected. The ALP activity of 0.2 and 0.06 mT PEMF and LLLT were comparable.

  14. The synthetic progestin, gestodene, affects functional biomarkers in neonatal rat osteoblasts through an estrogen receptor-related mechanism of action.

    Science.gov (United States)

    Enríquez, Juana; García, Gustavo; Herrero, Bertha; Larrea, Fernando

    2017-11-01

    Clinical studies have shown that gestodene (GDN), a potent third-generation synthetic progestin, affects bone resorption. However, its mode of action in bone cells is not fully understood. The aim of this study was to establish whether GDN affects bone directly or through its bioconversion to other metabolites with different biological activities. In this study, we investigated the effects of GDN and its A-ring reduced metabolites on proliferation, differentiation, and mineralization of calvarial osteoblasts isolated from neonatal rat and their capacity to displace [ 3 H]-E 2 at ER binding sites. In contrast to progesterone, gestodene did exert significant effects on osteoblast activities. The most striking finding was the observation that the A-ring reduced derivatives 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN, though to a lesser extent, had greater stimulatory effects on the osteoblast activity than those observed with GDN. The effects on osteoblast proliferation and differentiation induced by GDN-reduced derivatives were abolished by the antiestrogen ICI 182780, consistent with their binding affinities for the estrogen receptor. In addition, the presence of a 5α-reductase inhibitor or inhibitors of aldo-keto hydroxysteroid dehydrogenases abolished the GDN-induced enhancement of osteoblast differentiation. These results indicated that GDN is metabolized to the A-ring reduced metabolites with estrogen-like activities and through this mechanism, GDN may affect the osteoblast activity. Together, the data suggest that synthetic progestins derived from 19-nortestosterone such as GDN, have beneficial effects on bone due to their biotransformation into metabolites with intrinsic estrogenic activity.

  15. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

    Directory of Open Access Journals (Sweden)

    Amanda L. Smith

    2014-04-01

    Full Text Available Hypoxia-ischemia (HI; reduction in blood/oxygen supply is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA. Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P7, an age comparable to a term (GA 36–38 human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are

  16. Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets

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    DANIEL A CUNHA

    2006-01-01

    Full Text Available During pregnancy and the perinatal period of life, prolactin (PRL and other lactogenic substances induce adaptation and maturation of the stimulus-secretion coupling system in pancreatic β-cells. Since the SNARE molecules, SNAP-25, syntaxin 1, VAMP-2, and synaptotagmins participate in insulin secretion, we investigated whether the improved secretory response to glucose during these periods involves alteration in the expression of these proteins. mRNA was extracted from neonatal rat islets cultured for 5 days in the presence of PRL and from pregnant rats (17th-18th days of pregnancy and reverse transcribed. The expression of genes was analyzed by semi-quantitative RT-PCR assay. The expression of proteins was analyzed by Western blotting and confocal microscopy. Transcription and expression of all SNARE genes and proteins were increased in islets from pregnant and PRL-treated neonatal rats when compared with controls. The only exception was VAMP-2 production in islets from pregnant rats. Increased mRNA and protein expression of synaptotagmin IV, but not the isoform I, also was observed in islets from pregnant and PRL-treated rats. This effect was not inhibited by wortmannin or PD098059, inhibitors of the PI3-kinase and MAPK pathways, respectively. As revealed by confocal laser microscopy, both syntaxin 1A and synaptotagmin IV were immunolocated in islet cells, including the insulin-containing cells. These results indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion.

  17. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

    Directory of Open Access Journals (Sweden)

    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  18. Exposure of neonatal rats to anti-androgens induces penile mal-developments and infertility comparable to those induced by oestrogens.

    Science.gov (United States)

    Simon, L; Avery, L; Braden, T D; Williams, C S; Okumu, L A; Williams, J W; Goyal, H O

    2012-06-01

    We previously reported that oestrogen exposure in neonatal rats induced permanent infertility and malformed penis characterized by fat accumulation, which replaced most of the smooth muscle cells and cavernous spaces in the body of the penis, structures essential for erection. The objective of this study was to determine if reduced androgen production/action in the neonatal period, in the absence of exogenous oestrogen exposure, induces penile deformities similar to those caused by oestrogen. Male rats were treated from postnatal days 1-6 with GnRH antagonist antide (A, 10 mg/kg) or androgen receptor (AR) antagonist flutamide (F, 50 mg/kg) or F + A, with or without AR agonist dihydrotestosterone (DHT, 20 mg/kg). For comparison, pups received diethylstilbestrol (DES, 0.1 mg/kg), with or without DHT. Tissues were collected at ages 7 and 12 days and at adulthood. Flutamide alone decreased penile length and weight significantly (p penis and were infertile. In addition, reductions in penile length and weight were higher than in rats treated with F or A alone. DHT co-administration mitigated penile deformities in the DES group, but did not in the F + A group. Testicular testosterone was reduced by 70-95% at 7 or 12 days of age in all treated groups, except in the F group, which had threefold higher testosterone than controls. Collectively, data unequivocally show that reduced androgen production/action in the neonatal period, in the absence of oestrogen exposure, induces permanent infertility and malformed penis similar to that caused by oestrogen. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  19. Measuring mandibular ridge reduction

    International Nuclear Information System (INIS)

    Steen, W.H.A.

    1984-01-01

    This thesis investigates the mandibular reduction in height of complete denture wearers and overdenture wearers. To follow this reduction in the anterior region as well as in the lateral sections of the mandible, an accurate and reproducible measuring method is a prerequisite. A radiologic technique offers the best chance. A survey is given of the literature concerning the resorption process after the extraction of teeth. An oblique cephalometric radiographic technique is introduced as a promising method to measure mandibular ridge reduction. The reproducibility and the accuracy of the technique are determined. The reproducibility in the positioning of the mandible is improved by the introduction of a mandibular support which permits a precise repositioning of the edentulous jaw, even after long periods of investigation. (Auth.)

  20. Dabigatran ameliorates post-haemorrhagic hydrocephalus development after germinal matrix haemorrhage in neonatal rat pups.

    Science.gov (United States)

    Klebe, Damon; Flores, Jerry J; McBride, Devin W; Krafft, Paul R; Rolland, William B; Lekic, Tim; Zhang, John H

    2017-09-01

    We aim to determine if direct thrombin inhibition by dabigatran will improve long-term brain morphological and neurofunctional outcomes and if potential therapeutic effects are dependent upon reduced PAR-1 stimulation and consequent mTOR activation. Germinal matrix haemorrhage was induced by stereotaxically injecting 0.3 U type VII-S collagenase into the germinal matrix of P7 rat pups. Animals were divided into five groups: sham, vehicle (5% DMSO), dabigatran intraperitoneal, dabigatran intraperitoneal + TFLLR-NH 2 (PAR-1 agonist) intranasal, SCH79797 (PAR-1 antagonist) intraperitoneal, and dabigatran intranasal. Neurofunctional outcomes were determined by Morris water maze, rotarod, and foot fault evaluations at three weeks. Brain morphological outcomes were determined by histological Nissl staining at four weeks. Expression levels of p-mTOR/p-p70s6k at three days and vitronectin/fibronectin at 28 days were quantified. Intranasal and intraperitoneal dabigatran promoted long-term neurofunctional recovery, improved brain morphological outcomes, and reduced intracranial pressure at four weeks after GMH. PAR-1 stimulation tended to reverse dabigatran's effects on post-haemorrhagic hydrocephalus development. Dabigatran also reduced expression of short-term p-mTOR and long-term extracellular matrix proteins, which tended to be reversed by PAR-1 agonist co-administration. PAR-1 inhibition alone, however, did not achieve the same therapeutic effects as dabigatran administration.

  1. Treatment with UDP-glucose, GDNF, and memantine promotes SVZ and white matter self-repair by endogenous glial progenitor cells in neonatal rats with ischemic PVL.

    Science.gov (United States)

    Li, W-J; Mao, F-X; Chen, H-J; Qian, L-H; Buzby, J S

    2015-01-22

    Periventricular leukomalacia (PVL) is one of the foremost neurological conditions leading to long-term abnormalities in premature infants. Since it is difficult to prevent initiation of this damage in utero, promoting the innate regenerative potential of the brain after birth may provide a more feasible, prospective therapy for PVL. Treatment with UDP-glucose (UDPG), an endogenous agonist of G protein-coupled receptor 17 (GPR17) that may enhance endogenous self-repair potentiality, glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor associated with the growth and survival of nerve cells, and memantine, a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors that block ischemia-induced glutamate signal transduction, has been reported to achieve functional, neurological improvement in neonatal rats with PVL. The aim of the present study was to further explore whether UDPG, GDNF and/or memantine could promote corresponding self-repair of the subventricular zone (SVZ) and white matter (WM) in neonatal rats with ischemia-induced PVL. SVZ or WM tissue samples and cultured glial progenitor cells derived from a 5 day-old neonatal rat model of PVL were utilized for studying response to UDPG, GDNF and memantine in vivo and in vitro, respectively. Labeling with 5'-bromo-2'-deoxyuridine and immunofluorescent cell lineage markers after hypoxia-ischemia or oxygen-glucose deprivation (OGD) revealed that UDPG, GDNF and memantine each significantly increased glial progenitor cells and preoligodendrocytes (preOLs), as well as more differentiated immature and mature oligodendrocyte (OL), in both the SVZ and WM in vivo or in vitro. SVZ and WM glial cell apoptosis was also significantly reduced by UDPG, GDNF or memantine, both in vivo and in vitro. These results indicated that UDPG, GDNF or memantine may promote endogenous self-repair by stimulating proliferation of glial progenitor cells derived from both the SVZ and WM, activating their

  2. Transient inactivation of the ventral hippocampus in neonatal rats impairs the mesolimbic regulation of prefrontal glutamate release in adulthood

    DEFF Research Database (Denmark)

    Bortz, D M; Jørgensen, Christinna Vangsgaard; Mikkelsen, J D

    2014-01-01

    Cognitive deficits in schizophrenia (SZ) reflect maturational disruptions within a neural system that includes the ventral hippocampus (VH), nucleus accumbens (NAc), basal forebrain, and prefrontal cortex (PFC). A better understanding of these changes may reveal drug targets for more efficacious...... male Wistar rats that had received saline (Sal) or tetrodotoxin (TTX) as neonates (PD7) or as adolescents (PD32). The nucleus accumbens shell (NAcSh) was activated by NMDA infusions (0.05-0.30 μg/0.5 μL). Basal and evoked glutamate levels were measured amperometrically using a glutamate...

  3. In vivo longitudinal proton magnetic resonance spectroscopy on neonatal hypoxic-ischemic rat brain injury – Neuroprotective effects of acetyl-L-carnitine

    Science.gov (United States)

    Xu, Su; Waddell, Jaylyn; Zhu, Wenjun; Shi, Da; Marshall, Andrew D; McKenna, Mary C; Gullapalli, Rao P

    2014-01-01

    Purpose This study evaluated the longitudinal metabolic alterations after neonatal hypoxia-ischemia (HI) in rats and tested the neuroprotective effect of acetyl-L-carnitine (ALCAR) using in vivo proton short-TE Point-RESolved Spectroscopy method. Methods Rice-Vannucci model was used on 7-day-old Sprague-Dawley rats. Data were acquired from contralateral and ipsilateral cortex and hippocampus, respectively at 4 time points (24-h, 72-h, 7-d, 28-d) post-HI. The effect of subcutaneous administration of ALCAR (100 mg/kg) immediately after HI, at 4-h, 24-h, and 48-h post-HI was determined. Results Significant reductions in glutathione (p < 0.005), myo-inositol (p < 0.002), taurine (p < 0.001), and total creatine (p < 0.005) were observed at 24-h post injury compared to the control group in the ipsilateral hippocampus of the HI rat pups. ALCAR-treated-HI rats had lower levels of lactate and maintained total creatine at 24-h and had smaller lesion size compared to the HI only rats. Conclusion Severe oxidative, osmotic stress, impaired phosphorylation, and a preference for anaerobic glycolysis were found in the ipsilateral hippocampus in the HI pups at 24-h post injury. ALCAR appeared to have a neuroprotective effect if administered early after HI by serving as an energy substrate and promote oxidative cerebral energy producing and minimize anaerobic glycolysis. PMID:25461739

  4. Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia.

    Science.gov (United States)

    Brown, Russell W; Schlitt, Marjorie A; Owens, Alex S; DePreter, Caitlynn C; Cummins, Elizabeth D; Kirby, Seth L; Gill, W Drew; Burgess, Katherine C

    2018-01-01

    The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment. Rats were behaviorally sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38 to P45, and brain tissue was harvested at P46. Results revealed that neither housing condition reduced nicotine sensitization in NQ rats, whereas enrichment reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a neurotrophin important in dopamine plasticity. Results were complex, and revealed that NAcc GDNF was increased in animals given nicotine, regardless of housing condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent drug treatment and in NS-treated rats given nicotine, but did not increase GDNF in NS-treated controls compared to the isolated housing condition. This study demonstrates that environmental experience has a prominent impact on the behavioral and the neural plasticity NAcc response to nicotine in adolescence. © 2018 S. Karger AG, Basel.

  5. Reward or its denial during the neonatal period affects adult spatial memory and hippocampal phosphorylated cAMP response element-binding protein levels of both the neonatal and adult rat.

    Science.gov (United States)

    Diamantopoulou, A; Stamatakis, A; Panagiotaropoulos, T; Stylianopoulou, F

    2011-05-05

    Early life experiences, particularly mother-infant interactions, have been shown to influence adult coping and learning abilities via gene-environment interactions. We have developed a paradigm, in which mother contact is used as either a positive or a negative reinforcer in a T-maze, during postnatal days 10-13. In both neonates receiving (RER) or denied (DER) the expected reward, exposure to the memory test in the absence of the mother resulted in a remarkable increase in the number of pCREB immunopositive cells, when compared to their corresponding levels 2 h after the completion of the training process, but also to the levels of naïve animals. In the CA3 area, the pattern of pCREB immunoreactivity, when evaluated 2 h after the completion of the training on postnatal day 13 seemed to distinguish between the two different neonatal experiences in the T-maze, with the DER pups showing higher levels of pCREB immunopositive cells than the RER. Exposure to the Morris Water Maze (MWM) during adulthood revealed a memory advantage of the DER animals compared to the RER and the animals not exposed to the neonatal experience. Relevantly, in the DER animals an increased number of pCREB immunopositive cells was observed in the CA3 area even 24 h after the end of MWM training. When also measured after exposure to the probe trial, the number of pCREB immunopositive cells was again higher in the DER compared to the RER animals. In conclusion, we show that a learning experience involving discrepancy during the particularly plastic neonatal period is able to induce long-term effects, which result in enhanced adult hippocampal dependent spatial memory. Furthermore, our data document a role of plasticity molecules like pCREB in mediating hippocampal dependent learning and detection of novelty not only in adulthood, but also more importantly in the neonatal period of the rat. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Nonsyndromic Mandibular Symphysis Cleft

    Directory of Open Access Journals (Sweden)

    Leela Krishna Guttikonda

    2014-01-01

    Full Text Available Median cleft of lower lip and mandible is a rare congenital anomaly described as cleft number 30 of Tessier’s classification. In minor forms only lower lip cleft is seen. We report the case of a patient with median cleft of lower lip, severe ankyloglossia, cleft of mandibular symphysis, and residual cleft involving on right soft palate and associated with other facial clefts. These deformities were corrected in multiple stage procedure, consisting of release of the tongue from floor of the mouth and lower alveolus and fixation of the mandibular cleft done with right iliac bone graft using stainless steel miniplate.

  7. Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats.

    Science.gov (United States)

    Barrand, Sanna; Crowley, Tamsyn M; Wood-Bradley, Ryan J; De Jong, Kirstie A; Armitage, James A

    2017-01-01

    Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-valuefat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1) and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th) and dopamine reuptake transporter Slc6a3 (also known as Dat1). Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. Transcriptional changes identified in the hypothalamus of offspring of high fat diet mothers could alter neuronal projection formation during early development leading to abnormalities in the neuronal circuitry controlling appetite in later life, hence priming offspring to the development of obesity.

  8. Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats.

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    Sanna Barrand

    Full Text Available Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-value<0.05, including genes coding for proteins of the extra cellular matrix, particularly Collagen 1a1 (Col1a1, Col1a2, Col3a1, and the imprinted Insulin-like growth factor 2 (Igf2 gene. Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1 and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th and dopamine reuptake transporter Slc6a3 (also known as Dat1. Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. Transcriptional changes identified in the hypothalamus of offspring of high fat diet mothers could alter neuronal projection formation during early development leading to abnormalities in the neuronal circuitry controlling appetite in later life, hence priming offspring to the development of obesity.

  9. Frequency of unerupted mandibular third molar in mandibular angle fractures

    International Nuclear Information System (INIS)

    Abbasi, M.M.; Abbas, I.; Abbas, I.; Khan, N.; Hameed, H.; Zulfiqar, K.

    2012-01-01

    Background: Fractures of the mandibular angle are common and comprise 31% of all mandibular fractures. Multiple recent studies report a 2-3 fold increased risk for mandibular angle fractures when un-erupted mandibular third molars are present. The objective of this study was to assess the frequency of un-erupted mandibular third molar in mandibular angle fractures. Methods: This cross sectional study was conducted at the Department of Oral and Maxillofacial Surgery, Ayub Medical College, Abbottabad from April to October 2009. One hundred and two patients were included both from the outdoor and ward on consecutive non-probability sampling base. Data were recorded on a structured Performa and analysed using SPSS-16. Results: A hemi-mandible containing un-erupted mandibular third molar was seen to have a 1.41 times the risk of mandibular angle fracture then a hemi-mandible containing an erupted mandibular third molar. Conclusion: The presence of unerupted mandibular third molar is associated with an increased risk for mandibular angle fracture. (author)

  10. Effects of maternal ingestion of aroclor 1254 (PCB) on the development pattern of oxygen consumption and body temperature in neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Seo, B.W.; Meserve, L.A. [Bowling Green State Univ., OH (United States)

    1995-07-01

    Polychlorinated biphenyl (PCB) is an environmental pollutant that has been implicated in depression of reproductive success in Great Lakes gulls, production of congenital deformities in humans, and increased incidence of carcinogenesis in laboratory mice. PCB has also been shown to be a thyrotoxin in both adult and developing animals. Most recently, the hypothyroid effects of PCB exposure have been reported to elicit effects similar to those of hypothyroidism caused by other methods. This study was done to determine the effects of PCB ingestion in pregnant and lactating rats on the development of thermoregulation in neonatal animals. Body temperature and rate of oxygen consumption was evaluated in rat puts on days 4 through 14 after birth. Because the major thermomregulatory hormones are thyroid hormones, thyroid hormone status and thyroid weights were evaluated at the end of the study on postnatal day 15. 19 refs., 2 figs., 1 tab.

  11. Comparison of Therapeutic Effect of Anti-Cryptosporidium Nano-Nitazoxanide (NTZ with Free form of this Drug in Neonatal Rat

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    F. Sedighi

    2016-07-01

    Full Text Available Introduction & Objective: Cryptosporidiosis caused by Cryptosporidium, which is a protozoan parasite, has a worldwide distribution. The infection is through fecal-oral route, direct or indi-rect contact, food or water. The treatment of cryptosporidiosis is difficult and the anti-parasitic agents are not effective. The purpose of this study was encapsulation of nitazoxanide in solid lipid nano-particles (SLN and investigation of its anti-Cryptosporidium effect and its comparison with free drug in the neonatal rat. Materials & Methods: Nitazoxanide was encapsulated by HPH method with 2 mg/Kg concentra-tion in SLN nanoparticles. The oocysts were collected from calves and purified by sucrose floatation. A total of 72 Wistar neonatal rats were categorized in 6 groups of 12 rats including four infected groups treated by free drug, encapsulated nano drug, colloidal carriers without drug (SLN and olive oil; an infected control group and a healthy control group that received PBS. 5 × 105 of oocyts inoculated orally into the sample groups. Finally, intestine of each rat was homogenized in PBS by rotor and the homogenized material was passed through a sieve. Then, floated oocysts in sucrose solution were counted by hemocytometer. Results: Treatment by nitazoxanide significantly decreased the number of parasites in the treatment groups. This decrease at day 6 was more than day 3. Nano nitazoxanide had more effects on parasites than free drug. This difference at day 3 of treatment was not significant (p= 0.182 but at day 6 was statistically significant (P< 0.001. Conclusion: Using nano-nitazoxanide could be a more effective way in the treatment of Cryp-tosporidium infections. (Sci J Hamadan Univ Med Sci 2016; 23 (2:134-140

  12. Chronic low dose risperidone and clozapine alleviate positive but not negative symptoms in the rat neonatal ventral hippocampal lesion model of schizophrenia.

    Science.gov (United States)

    Rueter, Lynne E; Ballard, Michael E; Gallagher, Kelly B; Basso, Ana Maria; Curzon, Peter; Kohlhaas, Kathy L

    2004-11-01

    The rat neonatal ventral hippocampal (VH) ibotenic lesion model has been proposed as a developmental model of schizophrenia, based on evidence that it encompasses aspects of the disorder including psychomotor agitation (hyperactivity), deficits in prepulse inhibition (PPI), and deficits in social interaction (SI), measures presumed to reflect positive symptoms, sensory gating deficits and negative symptoms, respectively. However, validation of the model as a predictive pharmacological screening tool has been minimal. Determine the effects of a chronic 3-week low dose treatment of clozapine or risperidone on locomotor hyperactivity, PPI and SI in lesioned and control rats. Both clozapine, 2.5 mg/kg per day IP and risperidone, 0.1 mg/kg per day IP, reversed lesion-induced locomotor hyperactivity; however, the compounds also decreased locomotor activity in the non-lesioned controls. Clozapine 2.5 mg/kg per day and risperidone 0.1 mg/kg per day significantly attenuated lesion-induced PPI deficits. Neither compound induced a significant attenuation of lesion-induced SI deficits. In order to see if SI deficits required a higher dose of an antipsychotic, the dose of clozapine was increased to 4 mg/kg per day; however this dose induced such marked decreases in the activity and startle responses in the control rats, i.e. up to 74% decrease, that the effects on the lesioned rats could not be adequately interpreted. These data add further support to the neonatal VH lesion model as a predictive pharmacological screening assay for identifying compounds effective in the treatment of positive symptoms of schizophrenia. However, the usefulness of the model in detecting compounds effective in treating negative symptoms of schizophrenia is still in question.

  13. Angiogenesis during mandibular distraction osteogenesis.

    Science.gov (United States)

    Rowe, N M; Mehrara, B J; Luchs, J S; Dudziak, M E; Steinbrech, D S; Illei, P B; Fernandez, G J; Gittes, G K; Longaker, M T

    1999-05-01

    Recruitment of a blood supply is critical for successful bone induction and fracture healing. Despite the clinical success of distraction osteogenesis (DO), an analysis of angiogenesis during membranous bone DO has not been performed. The purpose of this study was to evaluate the temporal and spatial pattern of angiogenesis during mandibular DO. The right hemimandible of adult male rats was osteotomized, and a customized distraction device was applied. Following a 3-day latency period, distraction was begun at a rate of 0.25 mm twice daily for 6 days (3.0 mm total; 12% increase in mandibular length). Three animals each were sacrificed on days 2, 4, and 6 of distraction (D1, D2, and D3 respectively), or after 1, 2, or 4 weeks of consolidation (C1, C2, and C3 respectively). Two experienced pathologists reviewed the regenerate histology, and angiogenesis was assessed by counting the number of blood vessels per intermediate-power field (IPF). Statistical analysis was performed using analysis of variance, with p response during the early stages of distraction (D1). On average, 31.5+/-7.9 vessels were noted in each IPF examined during this time point. The number of blood vessels in the distraction regenerate decreased significantly during the later distraction time points, with approximately 14.0+/-2.0 and 14.7+/-3.5 blood vessels per IPF in sections obtained after days 4 and 6 of distraction (D2, D3) respectively. However, blood vessels at these time points took on a more mature histological pattern. During the consolidation period, the number of blood vessels noted in the regenerate decreased with 8.0+/-2.6, 9.3+/-2.1, and 4.0+/-2.0 vessels per IPF in sections obtained after 1, 2, or 4 weeks of consolidation (C1, C2, C3) respectively (p response associated with mandibular DO occurs primarily during the early stages of distraction. The authors hypothesize that as distraction continues, newly formed vessels likely undergo consolidation, thus forming more mature vessels

  14. Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1β and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

    Science.gov (United States)

    Neira-Peña, T; Rojas-Mancilla, E; Munoz-Vio, V; Perez, R; Gutierrez-Hernandez, M; Bustamante, D; Morales, P; Hermoso, M A; Gebicke-Haerter, P; Herrera-Marschitz, M

    2015-05-01

    Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1β and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1β and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.

  15. Activation of β-Adrenoceptors by Dobutamine May Induce a Higher Expression of Peroxisome Proliferator-Activated Receptors δ (PPARδ in Neonatal Rat Cardiomyocytes

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    Ming-Ting Chou

    2012-01-01

    Full Text Available Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of β1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells.

  16. The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model.

    Science.gov (United States)

    Mascarenhas, Vasco V; Casaccia, Marcelo; Fernandez-Martin, Alejandra; Marotta, Mario; Fontecha, Cesar G; Haddad, Sleiman; Knörr, Jorge; Soldado, Francisco

    2014-12-01

    We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58° at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats.

    Science.gov (United States)

    Schreiber, W B; St Cyr, S A; Jablonski, S A; Hunt, P S; Klintsova, A Y; Stanton, M E

    2013-07-01

    In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either free access to a running wheel on PD 30-41 and housing in a complex environment on PD 42-72 (wheel-running plus environmental complexity; WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80 ± 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS) paired with .8 mA footshock either immediately (delay conditioning) or after a 10-s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure impaired context and trace conditioning, but not short-delay conditioning. The WREC intervention did not reverse these deficits, despite increasing context-related freezing in ethanol-exposed and SI animals. Copyright © 2012 Wiley Periodicals, Inc.

  18. Attachment and proliferation of neonatal rat calvarial osteoblasts on Ti6Al4V: effect of surface chemistries of the alloy.

    Science.gov (United States)

    Lee, T M; Chang, E; Yang, C Y

    2004-01-01

    This study examined the cell attachment and proliferation of neonatal rat calvarial osteoblasts on Ti6Al4V alloy as affected by the surface modifications. The modifications could alter simultaneously the surface chemistries of the alloy (elemental difference of Ti, Al, V, Cu and Ni about 300-600mum thick examined by EDS) as well as the XPS nano-surface characteristics of oxides on the metal surface (chemistries of oxides, amphoteric OH group adsorbed on oxides, and oxide thickness). Three materials including two from modifications and a control were examined. It is argued that a slight change of the nano-surface characteristics of oxides as a result of the modifications neither alters the in vitro capability of Ca and P ion adsorption nor affects the metal ion dissolution behavior of the alloy. This implies that any influence on the cytocompatibility of the materials should only be correlated to the effect of surface chemistries of the alloy and the associated metal ion dissolution behavior of the alloy. The experimental results suggest that the cell response of neonatal rat calvarial osteoblasts on the Ti6Al4V alloy should neither be affected by the variation of surface chemistries of the alloy in a range studied.

  19. Effects of DAPT and Atoh1 overexpression on hair cell production and hair bundle orientation in cultured Organ of Corti from neonatal rats.

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    Li-Dong Zhao

    Full Text Available BACKGROUND: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. PRINCIPAL FINDINGS: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia.

  20. Dendritic morphology changes in neurons from the ventral hippocampus, amygdala and nucleus accumbens in rats with neonatal lesions into the prefrontal cortex.

    Science.gov (United States)

    Lazcano, Zayda; Solis, Oscar; Díaz, Alfonso; Brambila, Eduardo; Aguilar-Alonso, Patricia; Guevara, Jorge; Flores, Gonzalo

    2015-06-01

    Neonatal prefrontal cortex (nPFC) lesions in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the ventral hippocampus (VH) have been observed in post-mortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nPFC-lesions on the dendritic morphology of neurons from the VH, basolateral-amygdala (BLA) and the nucleus accumbens (NAcc) in rats. nPFC lesions were made on postnatal day 7 (PD7), after dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of PFC-lesions on locomotor activity caused by a novel environment. Adult animals with nPFC lesions showed a decreased spine density in pyramidal neurons from the VH and in medium spiny cells from the NAcc. An increased locomotion was observed in a novel environment for adult animals with a PFC-lesion. Our results indicate that PFC-lesions alter the neuronal dendrite morphology of the NAcc and the VH, suggesting a disconnection between these limbic structures. The locomotion paradigms suggest that dopaminergic transmission is altered in the PFC lesion model. This could help to understand the consequences of an earlier PFC dysfunction in schizophrenia. To evaluate possible dendritic changes in neonatal prefrontal cortex lesions in schizophrenia-related regions including nucleus accumbens, ventral hippocampus and basolateral amygdala, we used the Golgi-Cox stain samples at PD35 and PD70. Our results suggest that neonatal prefrontal cortex damage alters dendritic parameters in limbic regions, and this has potential implications for schizophrenia. © 2015 Wiley Periodicals, Inc.

  1. Nicotine-Like Effects of the Neonicotinoid Insecticides Acetamiprid and Imidacloprid on Cerebellar Neurons from Neonatal Rats

    Science.gov (United States)

    Kimura-Kuroda, Junko; Komuta, Yukari; Kuroda, Yoichiro; Hayashi, Masaharu; Kawano, Hitoshi

    2012-01-01

    Background Acetamiprid (ACE) and imidacloprid (IMI) belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs). Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development. Methodology/Principal Findings Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment—including proliferation, migration, differentiation, and morphological and functional maturation—can be observed in vitro. Using these cultures, an excitatory Ca2+-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca2+ influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca2+ influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine. Conclusions/Significance This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian n

  2. Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

    International Nuclear Information System (INIS)

    Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

    2010-01-01

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

  3. L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes.

    Science.gov (United States)

    Chao, Hung-Hsin; Liu, Ju-Chi; Hong, Hong-Jye; Lin, Jia-wei; Chen, Cheng-Hsien; Cheng, Tzu-Hurng

    2011-01-21

    Clinical use of doxorubicin is greatly limited by its severe cardiotoxic side effects. L-carnitine is a vitamin-like substance which has been successfully used in many cardiomyopathies, however, the intracellular mechanism(s) remain unclear. The objective of this study was set to evaluate the protective effect of L-carnitine on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). Primary cultured neonatal rat cardiomyocytes were treated with doxorubicin (1 µM) with or without pretreatment with L-carnitine (1-30 mM). Lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and flow cytometry measurement were used to assess cytotoxicity and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and chemiluminescence assay of superoxide production were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the quantity of cleaved caspase-3, cytosol cytochrome c, and Bcl-x(L) expression. L-carnitine inhibited doxorubicin-induced reactive oxygen species generation and NADPH oxidase activation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased Bcl-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, L-carnitine was found to increase the prostacyclin (PGI(2)) generation in cardiomyocytes. The siRNA transfection for PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and L-carnitine's protective effect. Furthermore, blockade the potential PGI(2) receptors, including PGI(2) receptors (IP receptors), and peroxisome proliferator-activated receptors alpha and delta (PPARα and PPARδ), revealed that the siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of L-carnitine. These findings suggest that L-carnitine protects cardiomyocytes from doxorubicin-induced apoptosis in part through PGI(2

  4. [Effect of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the neonatal rats].

    Science.gov (United States)

    Sang, Kui; Zhou, Ying; Li, Ming-xia

    2012-12-01

    To study the effect of hypoxia-inducible factor-1α (HIF-1α) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) of the neonatal rats through the study on the expression level of HIF-1α and its regulation factors: endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in blood serum and lung tissue. To make an HPH model of neonatal rats, 120 newborn Wistar rats were divided at random into two groups: HPH group and the regular oxygen controlled group with the same birthday. The rats of the two groups were put in the condition of hypoxia for 3, 5, 7, 10, 14, 21 days and then 10 rats of HPH group and control group were picked up, their mean pulmonary arterial pressure (mPAP), serum HIF-1α, and iNOS, and ET-1 content were tested, and finally their lung tissue was taken after they were sacrificed and the expression level of the gene mRNA of HIF-1α, iNOS and ET-1. (1) The rats experienced hypoxia for 3, 5, 7, 10, 14 or 21 days had an increasing mPAP: [8.47 ± 1.45, 10.04 ± 1.69, 10.89 ± 2.97, 16.96 ± 1.97, 13.01 ± 1.93, 21.04 ± 2.13 (mm Hg)], which had a significant differences compared with control groups [5.11 ± 1.06, 8.12 ± 1.11, 8.77 ± 0.92, 12.23 ± 1.78, 8.89 ± 0.89, 11.09 ± 1.64 (mm Hg)] (P rats in hypoxia group had a higher serum HIF-1α [0.83 ± 0.07, 0.84 ± 0.17, 0.97 ± 0.13, 1.10 ± 0.30, 0.92 ± 0.19 (pg/nmol)] than the control group [0.26 ± 0.20, 0.37 ± 0.16, 0.44 ± 0.18, 0.41 ± 0.23, 0.66 ± 0.18 (pg/nmol)] as they experienced hypoxia for 3, 5, 7, 10, and 14 days (P 0.05), and the content of serum iNOS after hypoxia for 14 or 21 days (4.56 ± 0.96, 5.86 ± 1.76) µmol/L was lower than that of the control group (10.35 ± 1.99, 8.44 ± 2.76) µmol/L (P rats and causedn a imbalance of ET-1 and NO. HIF-1α, ET-1 and iNOS altogether contributed to the occurrence and development of HPH in neonatal rats.

  5. What a Nostril Knows: Olfactory Nerve-Evoked AMPA Responses Increase while NMDA Responses Decrease at 24-h Post-Training for Lateralized Odor Preference Memory in Neonate Rat

    Science.gov (United States)

    Yuan, Qi; Harley, Carolyn W.

    2012-01-01

    Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and…

  6. Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

    Science.gov (United States)

    Gaztañaga, Mirari; Aranda-Fernández, P Ezequiel; Chotro, M Gabriela

    2015-09-01

    Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Mechanisms of Neuroprotection from Hypoxia-Ischemia (HI) Brain Injury by Up-regulation of Cytoglobin (CYGB) in a Neonatal Rat Model*

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    Tian, Shu-Feng; Yang, Han-Hua; Xiao, Dan-Ping; Huang, Yue-Jun; He, Gu-Yu; Ma, Hai-Ran; Xia, Fang; Shi, Xue-Chuan

    2013-01-01

    This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis. PMID:23585565

  8. Changes in the expression level of MAPK pathway components induced by monosodium glutamate-administration produce neuronal death in the hippocampus from neonatal rats.

    Science.gov (United States)

    Rivera-Carvantes, Martha Catalina; Jarero-Basulto, José Jaime; Feria-Velasco, Alfredo Ignacio; Beas-Zárate, Carlos; Navarro-Meza, Mónica; González-López, Mariana Berenice; Gudiño-Cabrera, Graciela; García-Rodríguez, Julio Cesar

    2017-12-04

    Excessive Glutamate (Glu) release may trigger excitotoxic cellular death by the activation of intracellular signaling pathways that transduce extracellular signals to the cell nucleus, which determines the onset of a death program. One such signaling pathway is the mitogen-activated protein kinases (MAPK), which is involved in both survival and cell death. Experimental evidences from the use of specific inhibitors supports the participation of some MAPK pathway components in the excitotoxicity mechanism, but the complete process of this activation, which terminates in cell damage and death, is not clearly understood. The present work, we investigated the changes in the expression level of some MAPK-pathway components in hippocampal excitotoxic cell death in the neonatal rats using an experimental model of subcutaneous monosodium glutamate (MSG) administration on postnatal days (PD) 1, 3, 5 and 7. Data were collected at different ages through PD 14. Cell viability was evaluated using fluorescein diacetate mixed with propidium iodide (FDA-PI), and the Nissl-staining technique was used to evaluate histological damage. Transcriptional changes were also investigated in 98 components of the MAPK pathway that are associated with cell damage. These results are an evidence of that repetitive use of MSG, in neonatal rats, induces cell damage-associated transcriptional changes of MAPK components, that might reflect a differential stage of both biochemical and molecular brain maturation. This work also suggests that some of the proteins evaluated such as phosphorylated retinoblastoma (pRb) protein, which was up-regulated, could regulate the response to excitotoxic through modulation of the process of re-entry into the cell cycle in the hippocampus of rats treated with MSG. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Th e eff ects of Nigella Sativa extract on renal tissue oxidative damage during neonatal and juvenile growth in propylthiouracil-induced hypothyroid rats.

    Science.gov (United States)

    Mohebbati, R; Hosseini, M; Haghshenas, M; Nazariborun, A; Beheshti, Farimah

    2017-04-25

    We investigated the effects of hydroalcoholic extract of Nigella sativa (NS) on renal tissue oxidative damage associated with propylthiouracil (PTU)-induced hypothyroidism during neonatal and juvenile growth in rats. Pregnant rats were divided into five groups designated as: 1) control; 2) propylthiouracil (PTU); 3) PTU-NS100; 4) PTU-NS200, and 5) PTU-NS400. All mothers except the control group received 0.005% PTU in their drinking water during lactation. Besides PTU, mothers in groups 3-5 received 100, 200, and 400 mg/kg of NS extract. After lactation period, the off spring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten male off springs of each group were randomly selected, blood samples collected, and the kidney tissues removed. The serum thyroxin concentration in PTU group was lower than control group and improved by extract. PTU increased the renal malondialdehyde (MDA), while reduced the total thiols concentrations and catalase (CAT) and superoxide dismutase (SOD) activity compared to control group. Administration of 200 and 400 mg/kg of NS extract decreased MDA level, while it increased the total thiols and 400 mg/kg increased CAT and SOD activity in renal tissues compared to PTU group. Serum creatinine and blood urea nitrogen (BUN) in PTU group was higher than in comparison with the control group. 400 mg/kg decreased creatinine, but both 200 and 400 mg/kg improved BUN concentration compared to PTU group. The results of this study demonstrate that the hydroalcoholic extract of NS has a protective effect on the renal tissue oxidative damage associated with PTU-induced hypothyroidism during neonatal and juvenile growth in rats.

  10. Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.

    Science.gov (United States)

    Xu, Li-Xiao; Lv, Yuan; Li, Yan-Hong; Ding, Xin; Wang, Ying; Han, Xing; Liu, Ming-Hua; Sun, Bin; Feng, Xing

    2017-03-28

    Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot. Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment. These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.

  11. Identification of Transmembrane Protease Serine 2 and Forkhead Box A1 As the Potential Bisphenol A Responsive Genes in the Neonatal Male Rat Brain

    Directory of Open Access Journals (Sweden)

    Takayoshi Ubuka

    2018-03-01

    Full Text Available Perinatal exposure of Bisphenol A (BPA to rodents modifies their behavior in later life. To understand how BPA modifies their neurodevelopmental process, we first searched for BPA responsive genes from androgen and estrogen receptor signaling target genes by polymerase chain reaction array in the neonatal male rat brain. We used a transgenic strain of Wistar rats carrying enhanced green fluorescent protein tagged to gonadotropin-inhibitory hormone (GnIH promoter to investigate the possible interaction of BPA responsive genes and GnIH neurons. We found upregulation of transmembrane protease serine 2 (Tmprss2, an androgen receptor signaling target gene, and downregulation of Forkhead box A1 (Foxa1, an ER signaling target gene, in the medial amygdala of male rats that were subcutaneously administered with BPA from day 1 to 3. Tmprss2-immunoreactive (ir cells were distributed in the olfactory bulb, cerebral cortex, hippocampus, amygdala, and hypothalamus in 3 days old but not in 1-month-old male rats. Density of Tmprss2-ir cells in the medial amygdala was increased by daily administration of BPA from day 1 to 3. Tmprss2 immunoreactivity was observed in 26.5% of GnIH neurons clustered from the ventral region of the ventromedial hypothalamic nucleus to the dorsal region of the arcuate nucleus of 3-day-old male rat hypothalamus. However, Tmprss2 mRNA expression significantly decreased in the amygdala and hypothalamus of 1-month-old male rats. Foxa1 mRNA expression was higher in the hypothalamus than the amygdala in 3 days old male rats. Intense Foxa1-ir cells were only found in the peduncular part of lateral hypothalamus of 3-day-old male rats. Density of Foxa1-ir cells in the hypothalamus was decreased by daily administration of BPA from day 1 to 3. Foxa1 mRNA expression in the hypothalamus also significantly decreased at 1 month. These results suggest that BPA disturbs the neurodevelopmental process and behavior of rats later in their life by

  12. Bilateral Mandibular Paramolars

    Science.gov (United States)

    Dhull, Rachita Singh; Panda, Swagatika; Acharya, Sonu; Yadav, Shweta; Mohanty, Gatha

    2014-01-01

    ABSTRACT Supernumerary tooth is a developmental anomaly and has been argued to arise from multiple etiologies. These teeth may remain embedded in the alveolar bone or can erupt into the oral cavity. They can cause a variety of complications in the develo­ping dentition. Supernumerary teeth can present in various forms and in any region of the mandible or maxilla, but have a predisposition for the anterior maxilla. Here is the presentation of a case of unusual location of supernumerary teeth located in between mandibular first and second molar region bilaterally. How to cite this article: Dhull KS, Dhull RS, Panda S, Acharya S, Yadav S, Mohanty G. Bilateral Mandibular Paramolars. Int J Clin Pediatr Dent 2014;7(1):40-42. PMID:25206236

  13. Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway.

    Science.gov (United States)

    Lai, Zhongmeng; Zhang, Liangcheng; Su, Jiansheng; Cai, Dongmiao; Xu, Qingxiu

    2016-01-01

    Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect. Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3β, p-GSK-3β by Western bolting and mPTP opening. Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3β. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it. Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3β pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. White matter and SVZ serve as endogenous sources of glial progenitor cells for self-repair in neonatal rats with ischemic PVL.

    Science.gov (United States)

    Mao, Feng-xia; Li, Wen-juan; Chen, Hui-jin; Qian, Long-hua; Buzby, Jeffrey S

    2013-10-16

    Mounting evidence suggests that endogenous progenitor cells may initiate cerebral WM repair. This study was designed to determine whether endogenous glial progenitor cells derived from either the subventricular zone (SVZ) or the white matter (WM) contribute to WM repair in a neonatal rat model of ischemic periventricular leukomalacia (PVL). Additionally, the role of G protein-coupled receptor 17 (GPR17), recently shown to act as a sensor for WM damage, was explored to assess its potential recruitment and activation of endogenous glial progenitor cells for such WM self-repair. Our in vivo and in vitro models consisted of five-day-old neonatal rats or cultured glial progenitor cells derived from both the SVZ and WM of these rats, randomly divided into sham/control and induced ischemic PVL/oxygen-glucose deprivation (OGD) groups. The WM of all PVL rats showed either mild or severe histopathological changes, with significantly increased in vivo apoptosis and poor myelination compared to those of the sham group. Significantly more apoptotic and necrotic cells were also detected in the OGD glial progenitor cell cultures derived from the SVZ and WM at all time intervals. The glial progenitor cells were significantly increased in both the SVZ (NG2⁺/GPR17⁻/BrdU⁺) and WM (NG2⁺/GPR17⁺/BrdU⁺) within 72 h after PVL; preOLs were also increased significantly in both the SVZ (O4⁺/GPR17⁻/BrdU⁺) and WM (O4⁺/GPR17⁺/BrdU⁺) within 7d after PVL in vivo or OGD in vitro. However, the more differentiated CNPase⁺/GPR17⁻/BrdU⁺ and MBP⁺/GPR17⁻/BrdU⁺ OLs in the SVZ and WM remained significantly less than those in the sham groups up to 14d or 21d after OGD or PVL, respectively. Hence, both the WM and SVZ were found to be potential endogenous sources of glial progenitor cells for WM repair in PVL rats. However their endogenous self-repair capacity appeared to be limited, since the more mature OLs did not completely recover from experimental ischemia, even

  15. Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of gestation and the impact of neonatal Fc receptor (FcRn) binding.

    Science.gov (United States)

    Thorn, Mitchell; Piche-Nicholas, Nicole; Stedman, Donald; Davenport, Scott W; Zhang, Ning; Collinge, Mark; Bowman, Christopher J

    2012-10-01

    There is concern about embryo-fetal exposure to antibody-based biopharmaceuticals based on the increase of such therapies being prescribed to women of childbearing potential. Therefore, there is a desire to better characterize embryo-fetal exposure of these molecules. The pregnant rat is a standard model for evaluating the potential consequences of exposure but placental transfer of antibody-based biopharmaceuticals is not well understood in this model. The relative embryo-fetal distribution of an antibody-based biopharmaceutical was evaluated in the rat. Bevacizumab (Avastin) was chosen as a tool antibody since it does not have significant target binding in the rat that might influence embryo-fetal biodistribution. Avastin was labeled with a fluorescent dye, characterized, and injected into pregnant rats at different gestation ages. Labeled Avastin in fetal tissues was visualized ex vivo using an IVIS 200 (Caliper, A PerkinElmer Company, Alameda, CA). Avastin localized to the fetus as early as 24-hr post intravenous injection of the dam, and was taken up by the fetus in a dose-dependent manner. Avastin was detectable in the developing embryo as early as gestation day 13 and continued to be transferred until the end of gestation. Fetal transfer of Avastins mutated in the portion of the antibody that binds the neonatal Fc receptor (FcRn) was tested in late gestation and was found to correlate with affinities of the mutant Avastin antibody to FcRn. The novel application of this imaging technology was used to characterize the onset and duration of Avastin maternal-fetal transfer in rats and the importance of FcRn binding. © 2012 Wiley Periodicals, Inc.

  16. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals.

    Science.gov (United States)

    Tian, Tian; Ni, Hong; Sun, Bao-liang

    2015-10-01

    The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy in adults, but it has not been extensively tested for its efficacy in neonatal seizure-induced brain damage. We have previously shown altered expression of zinc/lipid metabolism-related genes in hippocampus following penicillin-induced developmental model of epilepsy. In this study, we further investigated the effect of KD on the neurobehavioral and cognitive deficits, as well as if KD has any influence in the activity of zinc/lipid transporters such as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1 activities in neonatal rats submitted to flurothyl-induced recurrent seizures. Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT). On P28, they were further randomly divided into the seizure group without ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2). Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed from P35 to P49. Morris water maze test was performed during P51-P57. Then hippocampal mossy fiber sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced neurobehavioral toxicology and aberrant mossy fiber sprouting were blocked by KD. In parallel with these behavioral changes, rats treated with KD (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE, clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1 group. Our findings provide support for zinc/lipid transporter signals being potential targets for the treatment of neonatal seizure-induced brain damage by KD.

  17. Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.

    Science.gov (United States)

    Bunker, Suresh Kumar; Dandapat, Jagneshwar; Sahoo, Sunil Kumar; Roy, Anita; Chainy, Gagan B N

    2016-02-01

    Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter. © 2015 Wiley Periodicals, Inc.

  18. Effects of a chronic exposure to a highly palatable diet and its withdrawal, in adulthood, on cerebral Na+,K+-ATPase and plasma S100B in neonatally handled rats.

    Science.gov (United States)

    da S Benetti, Carla; Silveira, Patrícia P; Matté, Cristiane; Stefanello, Francieli M; Leite, Marina C; Gonçalves, Carlos Alberto S; Wyse, Angela T S; Dalmaz, Carla; Goldani, Marcelo Z

    2010-04-01

    We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long-term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na+,K+-ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non-handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na(+),K(+)-ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non-handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na+,K+-ATPase activity in both amygdala and hippocampus in non-handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non-handled animals also demonstrated increased frequency of head shaking in the open field after 24h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood. Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

  19. Efeito do tratamento com triptofano sobre parâmetros do comportamento alimentar em ratos adultos submetidos à desnutrição neonatal Effects of tryptophan on the eating behavior of adult rats with neonatal malnutrition

    Directory of Open Access Journals (Sweden)

    Judelita Carvalho-Santos

    2010-08-01

    period. The mean relative food intake and mean relative weight gain were then determined. The statistical analyses were done by the Student's t-test and ANOVA, followed by the Tukey test, with p<0.05. RESULTS: During the first 70 days of life, pups from protein-malnourished damns remained lighter than pups from well-nourished damns (p<0.01. Well-nourished rats treated with tryptophan (M=6.88, SD=0.05 ate less than those given saline (M=7.27, SD=0.08 (p<0.01 but weight was unaffected. No difference was found for the malnourished rats. CONCLUSION: In this study, neonatal protein restriction affected weight gain in rats. Furthermore, early malnutrition made adult rats resistant to the inhibitory effects of tryptophan on food intake.

  20. Avian-Pathogenic Escherichia coli Strains Are Similar to Neonatal Meningitis E. coli Strains and Are Able To Cause Meningitis in the Rat Model of Human Disease ▿

    Science.gov (United States)

    Tivendale, Kelly A.; Logue, Catherine M.; Kariyawasam, Subhashinie; Jordan, Dianna; Hussein, Ashraf; Li, Ganwu; Wannemuehler, Yvonne; Nolan, Lisa K.

    2010-01-01

    Escherichia coli strains causing avian colibacillosis and human neonatal meningitis, urinary tract infections, and septicemia are collectively known as extraintestinal pathogenic E. coli (ExPEC). Characterization of ExPEC strains using various typing techniques has shown that they harbor many similarities, despite their isolation from different host species, leading to the hypothesis that ExPEC may have zoonotic potential. The present study examined a subset of ExPEC strains: neonatal meningitis E. coli (NMEC) strains and avian-pathogenic E. coli (APEC) strains belonging to the O18 serogroup. The study found that they were not easily differentiated on the basis of multilocus sequence typing, phylogenetic typing, or carriage of large virulence plasmids. Among the APEC strains examined, one strain was found to be an outlier, based on the results of these typing methods, and demonstrated reduced virulence in murine and avian pathogenicity models. Some of the APEC strains tested in a rat model of human neonatal meningitis were able to cause meningitis, demonstrating APEC's ability to cause disease in mammals, lending support to the hypothesis that APEC strains have zoonotic potential. In addition, some NMEC strains were able to cause avian colisepticemia, providing further support for this hypothesis. However, not all of the NMEC and APEC strains tested were able to cause disease in avian and murine hosts, despite the apparent similarities in their known virulence attributes. Thus, it appears that a subset of NMEC and APEC strains harbors zoonotic potential, while other strains do not, suggesting that unknown mechanisms underlie host specificity in some ExPEC strains. PMID:20515929

  1. Effect of extracorporeal shock waves on subcondylar mandibular fractures.

    Science.gov (United States)

    Altuntaş, Emine Elif; Oztemur, Zekeriya; Ozer, Hatice; Müderris, Suphi

    2012-11-01

    The purpose of this pilot study was to evaluate the effects of extracorporeal shock wave therapy on healing of subcondylar mandibular fracture in rats. Unilateral subcondylar fracture in 20 Wistar albino rats was used as a fracture model. Each rat was anesthetized 1 day after surgery, and extracorporeal shock wave therapy was performed. On the 21st day after surgery, animals were killed. Mandibles were dissected, all soft tissues were removed after sacrifice, and fractured and nonfractured hemimandibles were obtained from each rat. Histologic analyses were performed by a single pathologist blinded to the samples. The specimens' mean score in bone fracture healing was 7 (1.09) (range, 6-9) in group 1 and 2.57 (1.62) (range, 1-6) in group 2. With respect to the specimens' bone fracture healing score, there was a statistically significant difference between the 2 groups. As a result, our study showed that extracorporeal shock wave therapy accelerated the improvement of fractures in experimentally induced subcondylar mandibular fracture in the rat mandible. We believe that reducing the duration of improvement in subcondylar mandibular fractures by intermaxillary fixation along with extracorporeal shock wave theraphy would contribute to preventing complications such as ankylosis, fibrosis, and hypomobility occuring because of prolonged fixation.

  2. Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

    Science.gov (United States)

    Durán-Carabali, L E; Arcego, D M; Odorcyk, F K; Reichert, L; Cordeiro, J L; Sanches, E F; Freitas, L D; Dalmaz, C; Pagnussat, A; Netto, C A

    2017-05-18

    Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.

  3. Neonatal treatment with fluoxetine reduces depressive behavior induced by forced swim in adult rats Tratamento neonatal com fluoxetina reduz o comportameto depressivo induzido pelo nado forçado em ratos adultos

    Directory of Open Access Journals (Sweden)

    Cristiano Mendes-da-Silva

    2002-12-01

    Full Text Available Serotonin plays a role at the pathophysiology of depression in humans and in experimental models. The present study investigated the depressive behavior and the weigh evolution in adult rats (60 days treated from the 1st to the 21st postnatal day with fluoxetine, a selective serotonin reuptake inhibitor (10 mg/kg, sc, daily. The depressive behavior was induced by the forced swim test (FST. The animals were submitted to two sessions of FST: 1st session for 15 min and the 2nd session 24h later, for 5 min. During the 2nd session the Latency of the Attempt of Escape (LAE and Behavioral Immobility (BI were appraised. The Fluoxetine group when compared to the Control group, showed an increase in LAE and a decrease in BI. The neonatal administration of fluoxetine reduced the depressive behavior in adult rats, possibly by increase in the brain serotonergic activity. This alteration can be associated to process of neuroadaptation.Estudos em humanos e em modelos experimentais demonstram que a serotonina (5-HT participa da fisiopatologia da depressão. O presente estudo investigou o comportamento depressivo e a evolução ponderal de ratos adultos jovens (60 dias tratados do 1º ao 21º dia pós-natal com fluoxetina, um inibidor seletivo de recaptação da serotonina, (10 mg/kg, sc, diariamente. A depressão experimental foi induzida através do teste de nado forçado (NF. Os animais foram submetidos a duas sessões de NF, a primeira por 15 min e a segunda após 24 h, por 5 min. Durante os 5 min de NF a latência da tentativa de fuga (LTF e o tempo de imobilidade (TI foram avaliados. O grupo tratado com fluoxetina apresentou aumento da LTF e redução do TI comparado ao controle. A administração neonatal de fluoxetina reduziu o comportamento depressivo em ratos adultos, possivelmente em função do aumento da atividade serotoninérgica cerebral. Esta alteração poderá estar relacionada a processos neuroadaptativos.

  4. The role of muscle imbalance in the pathogenesis of shoulder contracture after neonatal brachial plexus palsy: a study in a rat model.

    Science.gov (United States)

    Soldado, Francisco; Fontecha, Cesar G; Marotta, Mario; Benito, David; Casaccia, Marcelo; Mascarenhas, Vasco V; Zlotolow, Dan; Kozin, Scott H

    2014-07-01

    An internal rotation contracture of the shoulder is common after neonatal brachial plexus injuries due to subscapularis shortening and atrophy. It has been explained by 2 theories: muscle denervation and muscle imbalance between the internal and external rotators of the shoulder. The goal of this study was to test the hypothesis that muscle imbalance alone could cause subscapularis changes and shoulder contracture. We performed selective neurectomy of the suprascapular nerve in 15 newborn rats to denervate only the supraspinatus and the infraspinatus muscles, leaving the subscapularis muscle intact. After 4 weeks, passive shoulder external rotation was measured and a 7.2-T magnetic resonance imaging scan of the shoulders was used to determine changes in the infraspinatus and subscapularis muscles. The subscapularis muscle was weighed to determine the degree of mass loss. An additional group of 10 newborn rats was evaluated to determine the sectional muscle fiber size and muscle area of fibrosis by use of images from type I collagen immunostaining. There was a significant decrease in passive shoulder external rotation, with a mean loss of 66°; in the thickness of the denervated infraspinatus, with a mean loss of 40%; and in the thickness and weight of the non-denervated subscapularis, with mean losses of 28% and 25%, respectively. No differences were found in subscapularis muscle fiber size and area of fibrosis between shoulders after suprascapular nerve injury. Our study supports the theory that shoulder muscle imbalance is a cause of shoulder contracture in patients with neonatal brachial plexus palsy. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  5. The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.; Timchalk, Chuck; Bartels, M. J.; Mattsson, Joel L.

    2007-12-01

    There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactational exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.

  6. Rehabilitation training using complex motor learning rescues deficits in eyeblink classical conditioning in female rats induced by binge-like neonatal alcohol exposure.

    Science.gov (United States)

    Wagner, Jennifer L; Klintsova, Anna Y; Greenough, William T; Goodlett, Charles R

    2013-09-01

    Effective treatments for the behavioral and cognitive deficits in children with fetal alcohol spectrum disorders (FASD) are lacking, and translational approaches using animal models can help develop rational interventions. One such model, binge-like alcohol exposure in neonatal rats during the period of brain development comparable with that of the human third trimester, causes structural and functional damage to the cerebellum and disrupts cerebellar-dependent eyeblink classical conditioning. The eyeblink conditioning deficits first demonstrated in this rat model predicted the similar deficits subsequently demonstrated in children with FASD. The current study extends this translational approach by testing the hypothesis that rehabilitation training involving 20 days of training on traversal of an obstacle course (complex motor learning) would ameliorate the deficits on classical conditioning of eyeblink responses produced by the neonatal alcohol exposure. We have previously shown that this training stimulates cerebellar synaptic plasticity and improves alcohol-induced deficits on motor coordination tasks. The current studies found that rehabilitation training significantly attenuated alcohol-induced deficits in acquisition of eyeblink conditioning in females but not in males. These results are consistent with normalization of cerebellar-dependent learning, at least in alcohol-exposed females. These findings extend previous studies in this model suggesting that rehabilitation of adolescents with FASD using training with complex motor learning tasks could be effective in ameliorating functional impairments associated with cerebellar damage. Eyeblink classical conditioning deficits are now well documented in children with FASD and could serve as an evaluation measure to continue to develop therapeutic interventions such as complex motor learning. Copyright © 2013 by the Research Society on Alcoholism.

  7. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

    Science.gov (United States)

    Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

    2016-01-01

    Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

  8. Endothelin-1–Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups

    Science.gov (United States)

    Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H.

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1–ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1–ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. PMID:27760762

  9. Efeito da vagotomia troncular em ratos injetados na fase neonatal com glutamato monossódico: estudo biométrico Effect of vagotomy in rats neonatally injected with monosodium glutamate: biometry study

    Directory of Open Access Journals (Sweden)

    Fernando de Souza

    2001-03-01

    lesion could cause neuroendocrine obesity. Hypothalamic obesity could be reproduced through ventromedial hypothalamic lesion in animals and attenuated that by subdiafragmatic vagotomy (VT. VT decreased food intake and insulinemia. Injection of monosodium glutamate (MSG neonatally in rats produces adiposity, hyperphagia, without weight gain because it injures arcuate nucleus of the hypothalamus, site of growth hormone releasing hormone production. The purpose of this paper is to evaluate the MSG effect on weight, stature, Lee index (3 square root body weight/nasoanal length, gonadal fat (GF and food intake in rats and the VT effect on these parameters. Fifty-two male Wistar rats were used, divided into two groups of twenty-six animals each. SALINA group was subcutaneously injected with saline solution 12.5% (1.25 mg/g body weight/dayly/5days and MSG group was injected with MSG solution 24% (4 mg/g body weight/dayly/5 days, after the rats were born, in the posterior cervical region without adverse reaction. On the 30th day of life, the animals were divided into four groups and submitted to operation, sham operated groups (LAPSAL and LAPMSG and vagotomized groups (VTSAL and VTMSG. On operation day, weight, nasoanal length (NAL and Lee index were obtained. Food intake were obtained from the 30th day until 90th day. On 90th day, the animals were sacrificed and weight, NAL, Lee index and GF were obtained. Statistic analysis was performed by the Student’s t test. NAL was smaller and Lee index was greater in MSG group than in SALINA group on the 30th day. Weight gain and NAL were smaller and Lee index and GF were greater on the 90th day, and food intake from the 30th to 90th day period was greater in LAPMSG group than in LAPSAL group. Weight gain, Lee index and GF were smaller and NAL trended smaller in VTMSG group than in LAPMSG group on the 90th day. Food intake from the 30th to 60th day period was smaller and trended greater from the 60th to 90th day period in VTMSG group

  10. Mandibular appliance modulates condylar growth through integrins.

    Science.gov (United States)

    Marques, M Rubia; Hajjar, D; Franchini, K Gomes; Moriscot, A Sigari; Santos, M Fagundes

    2008-02-01

    Functional orthopedic therapy corrects growth discrepancies between the maxilla and mandible, possibly through postural changes in the musculature and modulation of the mandibular condylar cartilage growth. Using Wistar rats, we tested the hypothesis that chondrocytes respond to forces generated by a mandibular propulsor appliance by changes in gene expression, and that integrins are important mediators in this response. Immunohistochemical analyses demonstrated that the use of the appliance for different periods of time modulated the expression of fibronectin, alpha5 and alphav integrin subunits, as well as cell proliferation in the cartilage. In vitro, cyclic distension of condylar cartilage-derived cells increased fibronectin mRNA, as well as Insulin-like Growth Factor-I and II mRNA and cell proliferation. A peptide containing the Arginine-Glycine-Asparagine sequence (RGD), the main cell-binding sequence in fibronectin, blocked almost all these effects, confirming that force itself modulates the growth of the rat condylar cartilage, and that RGD-binding integrins participate in mechanotransduction.

  11. [Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction].

    Science.gov (United States)

    Li, Xiang-Wen; Li, Fang; Liu, Jing; Wang, Yan; Fu, Wei

    2016-11-01

    To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (Ptaurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (Ptaurine group had significantly higher mRNA expression of Rac than the FGR and control groups (Ptaurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (Ptaurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

  12. Effect of dopamine D3 antagonists on PPI in DBA/2J mice or PPI deficit induced by neonatal ventral hippocampal lesions in rats.

    Science.gov (United States)

    Zhang, Min; Ballard, Michael E; Kohlhaas, Kathy L; Browman, Kaitlin E; Jongen-Rêlo, Ana-Lucia; Unger, Liliane V; Fox, Gerard B; Gross, Gerhard; Decker, Michael W; Drescher, Karla U; Rueter, Lynne E

    2006-07-01

    Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animal models such as the test of prepulse inhibition of startle response (PPI) in rodents. It has been found that antipsychotics enhanced PPI in DBA mice and reversed the PPI deficit induced by neonatal ventral hippocampal (NVH) lesions in rats. However, the relative involvement of D(3) and D(2) receptors in these effects is unknown since all antipsychotics are D(2)/D(3) antagonists with limited binding preference at D(2) receptors. Therefore, in the current study, we investigated the influence of several dopamine antagonists with higher selectivity at D(3) vs D(2) receptors on PPI in DBA/2J mice and in NVH-lesioned rats. The PPI in DBA/2J mice was enhanced by the nonselective D(2)/D(3) antagonists, haloperidol at 0.3-3 mg/kg, or risperidone at 0.3-1 mg/kg, while PPI-enhancing effects were observed after the administration of higher doses of the preferential D(3)/D(2) antagonist, BP 897 at 8 mg/kg, and the selective D(3) antagonists, SB 277011 at 30 mg/kg and A-437203 at 30 mg/kg. No effect was observed following the treatment with the selective D(3) antagonist, AVE 5997 up to 30 mg/kg. The PPI deficits induced by NVH lesions were reversed by haloperidol but not by the more selective D(3) antagonists, A-437203 and AVE 5997. BP 897 enhanced PPI nonselectivity, that is, in both lesioned and nonlesioned rats. In summary, the present study indicates that PPI-enhancing effects induced by antipsychotics in DBA/2J mice and in NVH-lesioned rats are unlikely to be mediated by D(3) receptors.

  13. c-Fos induction in the brainstem following electrical stimulation of the trigeminal ganglion of chronically mandibular nerve-transected rats.

    Science.gov (United States)

    Abe, T; Shimoda, T; Urade, M; Hasegawa, M; Sugiyo, S; Takemura, M

    2013-12-01

    Neuronal excitability in the trigeminal sensory nuclei (TSN) changes after nerve transection. We examined the effects of chronic transection of the trigeminal nerve on the c-Fos-immunoreactivity in the TSN induced 2 h after 10 min of electrical stimulation of the trigeminal ganglion (TG) at C-fiber activating condition (1.0 mA, 5 ms, 5 Hz) in urethane-anesthetized rats. In the non-transected control rats, stimulation of the TG induced c-Fos-immunoreactive cells (c-Fos-IR cells) mostly in superficial layers (VcI/II) of the nucleus caudalis (Vc) in its full extent along the dorsomedial-ventrolateral axis, but modestly in the rostral TSN above the obex, the principal, oral, and interpolar nuclei. Three days, 1, 2, or 3 weeks after transection of the inferior alveolar (IAN), infraorbital, or masseteric nerves, the stimulation of the TG induced c-Fos-IR cells in the central terminal fields of the transected nerve in the rostral TSN and magnocellular zone of the Vc. However, the number of c-Fos-IR cells in the VcI/II decreased inside the central terminal fields of the transected nerve and increased outside the fields. These results indicate that transection of the trigeminal nerve increases the excitability of TSN neurons that receive inputs from injured mechanoreceptors and uninjured nociceptors, but decreases it from injured nociceptors. The altered c-Fos responses may imply mechanisms of neuropathic pain seen after nerve injury.

  14. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

    Science.gov (United States)

    2013-01-01

    Background Hypoxia induces microglial activation which causes damage to the developing brain. Microglia derived inflammatory mediators may contribute to this process. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation and cytokines production in brain injuries; however, its role in hypoxic injury remains uncertain. We investigate here TLR4 expression and its roles in neuroinflammation in neonatal rats following hypoxic injury. Methods One day old Wistar rats were subjected to hypoxia for 2 h. Primary cultured microglia and BV-2 cells were subjected to hypoxia for different durations. TLR4 expression in microglia was determined by RT-PCR, western blot and immunofluorescence staining. Small interfering RNA (siRNA) transfection and antibody neutralization were employed to downregulate TLR4 in BV-2 and primary culture. mRNA and protein expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) was assessed. Reactive oxygen species (ROS), nitric oxide (NO) and NF-κB levels were determined by flow cytometry, colorimetric and ELISA assays respectively. Hypoxia-inducible factor-1 alpha (HIF-1α) mRNA and protein expression was quantified and where necessary, the protein expression was depleted by antibody neutralization. In vivo inhibition of TLR4 with CLI-095 injection was carried out followed by investigation of inflammatory mediators expression via double immunofluorescence staining. Results TLR4 immunofluorescence and protein expression in the corpus callosum and cerebellum in neonatal microglia were markedly enhanced post-hypoxia. In vitro, TLR4 protein expression was significantly increased in both primary microglia and BV-2 cells post-hypoxia. TLR4 neutralization in primary cultured microglia attenuated the hypoxia-induced expression of TNF-α, IL-1β and iNOS. siRNA knockdown of TLR4 reduced hypoxia-induced upregulation of TNF-α, IL-1β, iNOS, ROS and NO in BV-2 cells. TLR4

  15. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

    Directory of Open Access Journals (Sweden)

    Yao Linli

    2013-02-01

    Full Text Available Abstract Background Hypoxia induces microglial activation which causes damage to the developing brain. Microglia derived inflammatory mediators may contribute to this process. Toll-like receptor 4 (TLR4 has been reported to induce microglial activation and cytokines production in brain injuries; however, its role in hypoxic injury remains uncertain. We investigate here TLR4 expression and its roles in neuroinflammation in neonatal rats following hypoxic injury. Methods One day old Wistar rats were subjected to hypoxia for 2 h. Primary cultured microglia and BV-2 cells were subjected to hypoxia for different durations. TLR4 expression in microglia was determined by RT-PCR, western blot and immunofluorescence staining. Small interfering RNA (siRNA transfection and antibody neutralization were employed to downregulate TLR4 in BV-2 and primary culture. mRNA and protein expression of tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β and inducible nitric oxide synthase (iNOS was assessed. Reactive oxygen species (ROS, nitric oxide (NO and NF-κB levels were determined by flow cytometry, colorimetric and ELISA assays respectively. Hypoxia-inducible factor-1 alpha (HIF-1α mRNA and protein expression was quantified and where necessary, the protein expression was depleted by antibody neutralization. In vivo inhibition of TLR4 with CLI-095 injection was carried out followed by investigation of inflammatory mediators expression via double immunofluorescence staining. Results TLR4 immunofluorescence and protein expression in the corpus callosum and cerebellum in neonatal microglia were markedly enhanced post-hypoxia. In vitro, TLR4 protein expression was significantly increased in both primary microglia and BV-2 cells post-hypoxia. TLR4 neutralization in primary cultured microglia attenuated the hypoxia-induced expression of TNF-α, IL-1β and iNOS. siRNA knockdown of TLR4 reduced hypoxia-induced upregulation of TNF-α, IL-1β, iNOS, ROS and

  16. [Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension].

    Science.gov (United States)

    Wang, Jian-Rong; Zhou, Ying; Sang, Kui; Li, Ming-Xia

    2013-02-01

    To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH). A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS. The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05). Pulmonary vascular

  17. T-cell seeding: neonatal transfer of anti-myelin basic protein T-cell lines renders Fischer rats susceptible later in life to the active induction of experimental autoimmune encephalitis.

    Science.gov (United States)

    Volovitz, Ilan; Mor, Felix; Machlenkin, Arthur; Machlenkin, Athur; Goldberger, Ofir; Marmor, Yotvat; Eisenbach, Lea; Cohen, Irun R; Cohen, Irun

    2009-09-01

    Fischer strain rats resist active induction of experimental autoimmune encephalomyelitis (EAE) following immunization with guinea-pig myelin basic protein (MBP) in complete Freund's adjuvant (CFA). Nevertheless, we now report that an encephalitogenic CD4(+) anti-MBP T-cell line could be developed from actively immunized Fischer rats. Adoptive transfer of the activated line mediated acute EAE in adult Fischer rats, but not in 1-day-old rats. Moreover, we found that both resting and activated anti-MBP T cells injected 1 day post-natally rendered these rats susceptible later in life to the active induction of EAE by immunization with MBP/CFA. The actively induced EAE manifested the accelerated onset of a secondary, memory-type response. Resting anti-MBP T cells injected even up to 2 weeks post-natally produced no clinical signs but seeded 50-100% of the recipients for an active encephalitogenic immune response to MBP. An earlier T-cell injection (1-2 days) produced a higher incidence and stronger response. The transferred resting T cells entered the neonatal spleen and thymus and proliferated there but did not change the total anti-MBP precursor number in adults. Splenocytes harvested from rats that were injected neonatally but not exposed to MBP in vivo proliferated strongly and produced significant amounts of interferon-gamma to MBP in vitro. Similar results were observed in rats injected with resting T-cell lines reactive to ovalbumin, suggesting that the neonatal injection of resting T cells specific for a self or for a foreign antigen can seed the immune system with the potential for an enhanced effector response to that antigen later in life.

  18. Neonatal sepsis

    Science.gov (United States)

    ... 1 week and before 3 months of age. Causes Neonatal sepsis can be caused by bacteria such as Escherichia ... and Tests Lab tests can help diagnose neonatal sepsis and identify the cause of the infection. Blood tests may include: Blood ...

  19. Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups

    OpenAIRE

    Moyer-Mileur, Laurie J.; Haley, Shannon; Gulliver, Kristina; Thomson, Anne; Slater, Hillarie; Barrett, Brett; Joss-Moore, Lisa A.; Callaway, Christopher; McKnight, Robert A.; Moore, Barry; Lane, Robert H.

    2011-01-01

    Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent a...

  20. Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic-Ischemic Injury in the Neonatal Rat.

    Science.gov (United States)

    Chu, Hannah X; Jones, Nicole M

    2016-03-01

    Hypoxia leads to activation of many cellular adaptive processes which are regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 consists of HIF-1α and HIF-1ß subunits and levels of HIF-1α protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1α and PHDs at various time points after hypoxia-ischemia (HI), using a neonatal rat model of HI brain injury. Sprague-Dawley rat pups (postnatal day 7) were anaesthetized and underwent right carotid artery occlusion and were then exposed to 6 % oxygen for 2.5 h at 37 °C. HI injured animals demonstrated a significant reduction in the size of the ipsilateral hemisphere, compared to sham controls. Protein analysis using western blotting and enzyme-linked immunosorbent assay showed that 24 h after HI, there was a significant increase in PHD3 protein and an increase of HIF-1α compared to controls. At the 72 h time point, there was a reduction in PHD3 protein, which appeared to relate to cellular loss. There were no changes in PHD1 or PHD2 protein levels after HI when compared to age-matched controls. Further studies are necessary to establish roles for the HIF-1 regulatory enzyme PHD3 in brain injury processes.

  1. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report.

    Science.gov (United States)

    Tran, Nhat-Thang; Alexandre-Gouabau, Marie-Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair-Yves; Winer, Norbert; Darmaun, Dominique

    2017-04-11

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulline or l-alanine by gavage from the sixth day of life until weaning, and were subsequently exposed to 10%-fructose in drinking water from weaning to 90 days of age. The oral glucose tolerance was tested (OGTT) at 70 days of age, and rats were sacrificed at 90 days of age. Pre-weaning citrulline supplementation failed to alter the growth trajectory, OGTT, plasma triglycerides, or fat mass accretion in adulthood; yet, it was associated with increased liver triglycerides, decreased liver total cholesterol, and a distinct liver lipidomic profile that may result in a predisposition to liver disease. We conclude that pre-weaning supplementation with citrulline does not impact early growth, but might impact liver fat metabolism in adulthood upon exposure to a high fructose diet.

  2. Maternal essential fatty acid supplementation increases zinc absorption in neonatal rats: relevance to the defect in zinc absorption in acrodermatitis enteropathica

    Energy Technology Data Exchange (ETDEWEB)

    Cunnane, S.C.

    1982-08-01

    Pregnant zinc deficient and zinc adequate rats were injection subcutaneously with evening primrose oil throughout gestation and for 3 days post partum. The nursing pups were injected intragastrically with /sup 65/Zn on day 3 of live and sacrifices 4 hr later. The % of the total injected zinc recovered in the carcass (minus the gut and gut contents) was significantly increased in those pups nursed by mothers injected with evening primrose oil, regardless of their dietary zinc intake. The fatty acid composition of the total lipid extract of the gut and gut contents of the neonates with increased /sup 65/Zn absorption indicated that these pups had higher proportions of arachidonic acid and other metabolites of linoleic than did those with lower /sup 65/Zn absorption. In other 3-day-old rat pups, intragastric injection of linoleic, gamma-linolenic or dihomo-gamma-linolenic acids along with the dose /sup 65/Zn very significantly increased /sup 65/Zn absorption in a dose-related manner. Arachindonic acid however had no significant effect on /sup 65/Zn absorption. Prostaglandin E1 caused a significant increase in /sup 65/Zn absorption but prostaglandin E2 had no consistant effect. Indomethacin caused a dosa-related inhibition of /sup 65/Zn absorption.

  3. The Effects of Acoustic White Noise on the Rat Central Auditory System During the Fetal and Critical Neonatal Periods: A Stereological Study.

    Science.gov (United States)

    Salehi, Mohammad Saied; Namavar, Mohammad Reza; Tamadon, Amin; Bahmani, Raziyeh; Jafarzadeh Shirazi, Mohammad Reza; Khazali, Homayoun; Dargahi, Leila; Pandamooz, Sareh; Mohammad-Rezazadeh, Farzad; Rashidi, Fatemeh Sadat

    2017-01-01

    To evaluate the effects of long-term, moderate level noise exposure during crucial periods of rat infants on stereological parameters of medial geniculate body (MGB) and auditory cortex. Twenty-four male offspring of 12 pregnant rats were divided into four groups: fetal-to-critical period group, which were exposed to noise from the last 10 days of fetal life till postnatal day (PND) 29; fetal period group that exposed to noise during the last 10 days of fetal life; critical period group, exposed to noise from PND 15 till PND 29, and control group. White noise at 90 dB for 2 h per day was used. Variance for variables was performed using Proc GLM followed by mean comparison by Duncan's multiple range test. Numerical density of neurons in MGB of fetal-to-critical period group was lower than control group. Similar results were seen in numerical density of neurons in layers IV and VI of auditory cortex. Furthermore, no significant difference was observed in the volume of auditory cortex among groups, and only MGB volume in fetal-to-critical period group was higher than other groups. Estimated total number of neurons in MGB was not significantly different among groups. It seems necessary to prevent long-term moderate level noise exposure during fetal-to-critical neonatal period.

  4. Melatonin protects against blood-brain barrier damage by inhibiting the TLR4/ NF-κB signaling pathway after LPS treatment in neonatal rats.

    Science.gov (United States)

    Hu, Yingying; Wang, Zhouguang; Pan, Shulin; Zhang, Hongyu; Fang, Mingchu; Jiang, Huai; Zhang, Hao; Gao, Zhengzheng; Xu, Kebin; Li, Zhenmao; Xiao, Jian; Lin, Zhenlang

    2017-05-09

    Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms. HII animal model was conducted by receiving lipopolysaccharide followed by 90 min hypoxia-ischaemia in postnatal day 2 Sprague-Dawley rat pups. Melatonin was injected intraperitoneally 1 h before lipopolysaccharide injection and then once a day for 1 week to evaluate the long-term effects. In this study, we demonstrated that melatonin administration inhibited the disruption of BBB permeability and improved the white matter recovery in HII model rats. Melatonin significantly attenuated the degradation of junction proteins and the neuroprotective role was related to the inhibition of microglial toll-like receptor 4/ nuclear factor-kappa B signaling pathway both in vivo and in vitro. Taken together, our data demonstrated that therapeutic strategies targeting inflammation might be suitable for the therapy of preserving BBB integrity after HII.

  5. The Effects of Acoustic White Noise on the Rat Central Auditory System During the Fetal and Critical Neonatal Periods: A Stereological Study

    Directory of Open Access Journals (Sweden)

    Mohammad Saied Salehi

    2017-01-01

    Full Text Available Aim: To evaluate the effects of long-term, moderate level noise exposure during crucial periods of rat infants on stereological parameters of medial geniculate body (MGB and auditory cortex. Materials and Methods: Twenty-four male offspring of 12 pregnant rats were divided into four groups: fetal-to-critical period group, which were exposed to noise from the last 10 days of fetal life till postnatal day (PND 29; fetal period group that exposed to noise during the last 10 days of fetal life; critical period group, exposed to noise from PND 15 till PND 29, and control group. White noise at 90 dB for 2 h per day was used. Statistical Analysis Used: Variance for variables was performed using Proc GLM followed by mean comparison by Duncan’s multiple range test. Results: Numerical density of neurons in MGB of fetal-to-critical period group was lower than control group. Similar results were seen in numerical density of neurons in layers IV and VI of auditory cortex. Furthermore, no significant difference was observed in the volume of auditory cortex among groups, and only MGB volume in fetal-to-critical period group was higher than other groups. Estimated total number of neurons in MGB was not significantly different among groups. Conclusion: It seems necessary to prevent long-term moderate level noise exposure during fetal-to-critical neonatal period.

  6. Chronic lung injury in the neonatal rat: up-regulation of TGFβ1 and nitration of IGF-R1 by peroxynitrite as likely contributors to impaired alveologenesis.

    Science.gov (United States)

    Belcastro, Rosetta; Lopez, Lianet; Li, Jun; Masood, Azhar; Tanswell, A Keith

    2015-03-01

    Postnatal alveolarization is regulated by a number of growth factors, including insulin-like growth factor-I (IGF-I) acting through the insulin-like growth factor receptor-1 (IGF-R1). Exposure of the neonatal rat lung to 60% O2 for 14 days results in impairments of lung cell proliferation, secondary crest formation, and alveologenesis. This lung injury is mediated by peroxynitrite and is prevented by treatment with a peroxynitrite decomposition catalyst. We hypothesized that one of the mechanisms by which peroxynitrite induces lung injury in 60% O2 is through nitration and inactivation of critical growth factors or their receptors. Increased nitration of both IGF-I and IGF-R1 was evident in 60% O2-exposed lungs, which was reversible by concurrent treatment with a peroxynitrite decomposition catalyst. Increased nitration of the IGF-R1 was associated with its reduced activation, as assessed by IGF-R1 phosphotyrosine content. IGF-I displacement binding plots were conducted in vitro using rat fetal lung distal epithelial cells which respond to IGF-I by an increase in DNA synthesis. When IGF-I was nitrated to a degree similar to that observed in vivo there was minimal, if any, effect on IGF-I displacement binding. In contrast, nitrating cell IGF-R1 to a similar degree to that observed in vivo completely prevented specific binding of IGF-I to the IGF-R1, and attenuated an IGF-I-mediated increase in DNA synthesis. Additionally, we hypothesized that peroxynitrite also impairs alveologenesis by being an upstream regulator of the growth inhibitor, TGFβ1. That 60% O2-induced impairment of alveologenesis was mediated in part by TGFβ1 was confirmed by demonstrating an improvement in secondary crest formation when 60% O2-exposed pups received concurrent treatment with the TGFß1 activin receptor-like kinase, SB 431542. That the increased TGFβ1 content in lungs of pups exposed to 60% O2 was regulated by peroxynitrite was confirmed by its attenuation by concurrent treatment

  7. Action of selective serotonin reuptake inhibitor on aggressive behavior in adult rat submitted to the neonatal malnutrition.

    Science.gov (United States)

    Medeiros, J M; Silva, C M; Sougey, E B; Costa, J A; Castro, C M; Castro, R M

    2001-09-01

    The effect of the malnutrition during suckling on the aggressiveness was investigated in adult rats treated or not with citalopram, a selective serotonin reuptake inhibitor (SSRI). The animals were divided into two groups according to the diet used: nourished group - the rats received the control diet with 23% protein during the life; and malnourished group - the rats had its mothers submitted to diet with 7.8% protein during suckling. At 120 days of age, each group was sub-divided according to the treatment: acute - consisting a single i.p. injection of saline solution or 20-mg/Kg citalopram; chronic - consisting the single injections (1 per day during 14 days) of saline or 20 mg/Kg citalopram. The acute or chronic treatment with SSRI reduces aggressive response in nourished rats, but not in malnourished ones. Thus, the malnutrition during the critical period of brain development seems to induce durable alterations in the function of the serotoninergic neurotransmission

  8. Radiological classification of mandibular fractures

    International Nuclear Information System (INIS)

    Mihailova, H.

    2009-01-01

    Mandibular fractures present the biggest part (up to 97%) of the facial bone fractures. Method of choice for diagnosing of mandibular fractures is conventional radiography. The aim of the issue is to present an unified radiological classification of mandibular fractures for the clinical practice. This classification includes only those clinical symptoms of mandibular fracture which could be radiologically objectified: exact anatomical localization (F1-F6), teeth in fracture line (Ta,Tb), grade of dislocation (D I, D II), occlusal disturbances (O(+), O(-)). Radiological symptoms expressed by letter and number symbols are systematized in a formula - FTDO of mandibular fractures similar to TNM formula for tumours. FTDO formula expresses radiological diagnose of each mandibular fracture but it doesn't include neither the site (left or right) of the fracture, nor the kind and number of fractures. In order to express topography and number of fractures the radiological formula is transformed into a decimal fraction. The symbols (FTD) of right mandible fracture are written in the numerator and those of the left site - in the denominator. For double and multiple fractures between the symbols for each fracture we put '+'. Symbols for occlusal disturbances are put down opposite, the fractional line. So topographo-anatomical formula (FTD/FTD)xO is formed. In this way the whole radiological information for unilateral, bilateral, single or multiple fractures of the mandible is expressed. The information in the radiological topography anatomic formula, resp. from the unified topography-anatomic classification ensures a quick and exact X-ray diagnose of mandibular fracture. In this way contributes to get better, make easier and faster X-ray diagnostic process concerning mandibular fractures. And all these is a precondition for prevention of retardation of the diagnosis mandibular fracture. (author)

  9. Effects of systemic administration of ciliary neurotrophic factor on Bax and Bcl-2 proteins in the lumbar spinal cord of neonatal rats after sciatic nerve transection

    Directory of Open Access Journals (Sweden)

    A.C.S. Rezende

    2008-11-01

    Full Text Available Ciliary neurotrophic factor (CNTF is a cytokine that plays a neuroprotective role in relation to axotomized motoneurons. We determined the effect of daily subcutaneous doses of CNTF (1.2 µg/g for 5 days; N = 13 or PBS (N = 13 on the levels of mRNA for Bcl-2 and Bax, as well as the expression and inter-association of Bcl-2 and Bax proteins, and the survival of motoneurons in the spinal cord lumbar enlargement of 2-day-old Wistar rats after sciatic nerve transection. Five days after transection, the effects were evaluated on histological and molecular levels using Nissl staining, immunoprecipitation, Western blot analysis, and reverse transcriptase-polymerase chain reaction. The motoneuron survival ratio, defined as the ratio between the number of motoneurons counted on the lesioned side vs those on the unlesioned side, was calculated. This ratio was 0.77 ± 0.02 for CNTF-treated rats vs 0.53 ± 0.02 for the PBS-treated controls (P < 0.001. Treatment with CNTF modified the level of mRNA, with the expression of Bax RNA decreasing 18% (with a consequent decrease in the level of Bax protein, while the expression of Bcl-2 RNA was increased 87%, although the level of Bcl-2 protein was unchanged. The amount of Bcl-2/Bax heterodimer increased 91% over that found in the PBS-treated controls. These data show, for the first time, that the neuroprotective effect of CNTF on neonatal rat axotomized motoneurons is associated with a reduction in free Bax, due to the inhibition of Bax expression, as well as increased Bcl-2/Bax heterodimerization. Thus, the neuroprotective action of the CNTF on axotomized motoneurons can be related to the inhibition of this apoptotic pathway.

  10. [The profile surgery. Mandibular osteotomies].

    Science.gov (United States)

    Sancho, M A; Grande, C; Parri, F J; Rivera, A; Sarget, R; Morales, L

    1996-04-01

    During the years 1987-1994, 31 mandibular osteotomies have been performed in 25 patients, 15 had mandibular alteration alone, 10 of them with prognatism, 2 with microretrognatia and 3 with chin hipoplasia. The other 10 had a combined maxillary-mandibular alteration with hipoplasia and maxillary retrussion. The preoperative work-up included cephalometric and dental study, and a cast model was done to asses the theoretical benefic of the osteotomy. All these patients underwent orthodontic treatment before and after surgery. The results have been good or very good in 96% of the cases. The ortognatic surgery offers significant aesthetic and functional improvement to these patients.

  11. Malignant mandibular tumors: two case reports of rare mandibular ...

    African Journals Online (AJOL)

    Mandibular lesions can be benign or malignant, malignant being less common. The most common malignant tumor of mandible is squamous cell carcinoma. Others are ameloblastic carcinoma, osteosarcoma, chondrosarcoma, fibrosarcoma, malignant fibrous histiocytoma and metastasis. Osteosarcoma is a bone tumor.

  12. Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a neonatal rat model of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Aurelie Le Mandat Schultz

    Full Text Available BACKGROUND: The etiology of necrotizing enterocolitis (NEC results from a combination of several risk factors that act synergistically and occurs in the same circumstances as those which lead to innate immunity activation. Pattern recognition molecules could be an important player in the initiation of an exaggerated inflammatory response leading to intestinal injury in NEC. METHODOLOGY/PRINCIPAL FINDINGS: We specifically evaluated intestinal epithelial cell (IEC expression of Toll-like receptor 2 (TLR-2, TLR-4, NOD2 and phosphorylated NF-kappaB (pNF-kappaB after mucosal injury in a rat model of NEC induced by prematurity, systemic hypoxia, and a rich protein formula. In the control group (group 1, neonatal rats were full-term and breast-fed; in the experimental groups, rat pups were preterm at day 21 of gestation and rat-milk fed (group 2 or hand-gavaged with a protein rich formula after a hypoxia-reoxygenation procedure (group 3. Morphological mucosal changes in the small bowel were scored on hematoxylin- and eosin-stained sections. Immunohistochemistry was performed on frozen tissue sections using anti TLR-2 and active pNF-kappaB p65 antibodies. Real-time RT-PCR was performed to assess mRNA expression of NOD2, TLR-2 and TLR-4. Proliferation and apoptosis were studied in paraffin sections using anti Ki-67 and caspase-3 antibodies, respectively. The combination of immaturity, protein rich formula and a hypoxia-reoxygenation procedure induces pathological mucosal damage consistent with NEC. There was an overexpression of TLR-2, and pNF-kappaB in IECs that was correlated with the severity of mucosal damage, together with an increase of apoptotic IECs and markedly impaired proliferation. In addition, these immunological alterations appeared before severe mucosal damage. TLR-2 mRNA were also increased in NEC together with TLR-4 mRNA using real-time RT-PCR whereas NOD2 expression was unchanged. CONCLUSIONS/SIGNIFICANCE: These results show that this

  13. A study of mandibular foramen and mandibular canal using orthopantomograms

    International Nuclear Information System (INIS)

    Kim, Hee Sang; Kim, Jhai Dhuck

    1983-01-01

    The mandibular canal must be considered carefully during surgical treatment, especially surgical extraction of the impacted tooth and intraosseous implant because it contains the important inferior alveolar nerve and vessel. Th e author investigated the curvature of the mandibular canal, the positional frequency of mandibular foramen to the occlusal plane and gonial angle and the positional frequency of the mental foramen to the tooth site using orthopantomorgrams. The materials considered of 295 orthopantomograms divided into seven groups ranging from the first decade to 6th decade. The results were as follows: 1. The position of mandibular foramen was most frequently below occlusal plane in Group I (78.6%) and Group II (71.2%) , above occlusal plane in Group III (63.0%), Group IV (71.1%), Group V (57.6%), Group VI (76.7%) and Group VII (70.0%). 2. The curvature of mandibular canal was 142.82 .deg. in Group I, 142.09 .deg. in Group II, 139.34 .deg. in Group III, 141.48 .deg. in Group IV, 138.45 .deg. in Group V, 140.77 .deg. in Group VI and 143.89 .deg. in Group VII. 3. The gonial angle was 125.82 .deg. in Group I, 123.18 .deg. in Group II, 124.06 .deg. in Group III, 120.45 .deg. in Group IV, 121.12 .deg. in Group V, 121.63 .deg. in Group VI and 121.24 .deg. in Group VII. 4. The position of the mental foramen was most frequently below the apex of mandibular first premolar in Group I ( 57.2%), between the apex of mandibular first and second premolar in Group II (59.6%) and Group III (48.9%), and below the apex of mandibular second premolar in Group IV (39.2%), Group V (48.5%) Group VI (46.7%) and Group VII (56.4%).

  14. A study of mandibular foramen and mandibular canal using orthopantomograms

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Sang; Kim, Jhai Dhuck [Department of Dentistry, Graduate School, Chosun University, Kwangju (Korea, Republic of)

    1983-11-15

    The mandibular canal must be considered carefully during surgical treatment, especially surgical extraction of the impacted tooth and intraosseous implant because it contains the important inferior alveolar nerve and vessel. Th e author investigated the curvature of the mandibular canal, the positional frequency of mandibular foramen to the occlusal plane and gonial angle and the positional frequency of the mental foramen to the tooth site using orthopantomorgrams. The materials considered of 295 orthopantomograms divided into seven groups ranging from the first decade to 6th decade. The results were as follows: 1. The position of mandibular foramen was most frequently below occlusal plane in Group I (78.6%) and Group II (71.2%) , above occlusal plane in Group III (63.0%), Group IV (71.1%), Group V (57.6%), Group VI (76.7%) and Group VII (70.0%). 2. The curvature of mandibular canal was 142.82 .deg. in Group I, 142.09 .deg. in Group II, 139.34 .deg. in Group III, 141.48 .deg. in Group IV, 138.45 .deg. in Group V, 140.77 .deg. in Group VI and 143.89 .deg. in Group VII. 3. The gonial angle was 125.82 .deg. in Group I, 123.18 .deg. in Group II, 124.06 .deg. in Group III, 120.45 .deg. in Group IV, 121.12 .deg. in Group V, 121.63 .deg. in Group VI and 121.24 .deg. in Group VII. 4. The position of the mental foramen was most frequently below the apex of mandibular first premolar in Group I (57.2%), between the apex of mandibular first and second premolar in Group II (59.6%) and Group III (48.9%), and below the apex of mandibular second premolar in Group IV (39.2%), Group V (48.5%) Group VI (46.7%) and Group VII (56.4%).

  15. Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

    -quantitative analysis. MicroPET images were analyzed using PMOD software and registered to an average Sprague-Dawley rat MRI brain atlas to acquire data in limbic and cortical regions of interest. Results: In behavioural testing DOM60, and to a lesser extent DOM20 rats, spent more time in the periphery during the open......-Dawley rats (n=6-7 per group) were injected (s.c.) daily from postnatal day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test...... and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner, to measure α2 adrenoceptor binding. The volume of distribution (VT...

  16. Deferoxamine expedites consolidation during mandibular distraction osteogenesis.

    Science.gov (United States)

    Donneys, Alexis; Deshpande, Sagar S; Tchanque-Fossuo, Catherine N; Johnson, Kelsey L; Blough, Jordan T; Perosky, Joseph E; Kozloff, Kenneth M; Felice, Peter A; Nelson, Noah S; Farberg, Aaron S; Levi, Benjamin; Buchman, Steven R

    2013-08-01

    A limitation of mandibular distraction osteogenesis (DO) is the length of time required for consolidation. This drawback subjects patients to possible pin-site infections, as well as a prolonged return to activities of normal daily living. Developing innovative techniques to abridge consolidation periods could be immensely effective in preventing these problematic morbidities. Deferoxamine (DFO) is an angiogenic activator that triggers the HIF-1α pathway through localized iron depletion. We previously established the effectiveness of DFO in enhancing regenerate vascularity at a full consolidation period (28 days) in a murine mandibular DO model. To investigate whether this augmentation in vascularity would function to accelerate consolidation, we progressively shortened consolidation periods prior to μCT imaging and biomechanical testing (BMT). Three time points (14d, 21d and 28d) were selected and six groups of Sprague-Dawley rats (n = 60) were equally divided into control (C) and experimental (E) groups for each time period. Each group underwent external fixator placement, mandibular osteotomy, and a 5.1 mm distraction. During distraction, the experimental groups were treated with DFO injections into the regenerate gap. After consolidation, mandibles were imaged and tension tested to failure. ANOVA was conducted between groups, and p consolidation the experimental group demonstrated significant increases in bone volume fraction (BVF), bone mineral density (BMD) and ultimate load (UL) in comparison to non-treated controls. The benefit of treatment was further substantiated by a striking 100% increase in the number of bony unions at this early time-period (C:4/10 vs. E:8/10). Furthermore, metrics of BVF, BMD, Yield and UL at 14 days with treatment demonstrated comparable metrics to those of the fully consolidated 28d control group. Based on these findings, we contend that augmentation of vascular density through localized DFO injection delivers an efficient means

  17. IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2017-12-01

    Full Text Available Interleukin-33 (IL-33 is a novel identified chromatin-associated cytokine of IL-1 famil