Sample records for rats treated neonatally

  1. Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy. (United States)

    Reis, Amanda Maria Sena; Ribeiro, Lorena Gabriela Rocha; Ocarino, Natália de Melo; Goes, Alfredo Miranda; Serakides, Rogéria


    Caffeine is an active alkaloid that can cause damage to bones in formation during prenatal life into adulthood. This compound can pass across the placenta and into the mother's milk, causing a reduction in bone formation, growth and mass. The objective of this study was to examine the osteogenic potential of osteoblasts extracted from neonatal rats born to mothers treated with caffeine throughout pregnancy. Twenty-four adult Wistar rats were randomly divided into four groups, consisting of one control group and three groups that were treated with 25, 50, or 100 mg/kg of caffeine by an oral-gastric probe throughout the duration of the experimental period (pregnancy). At birth, three puppies from each dam in each group were euthanized, and osteoblasts were extracted from the calvaria of these pups for in vitro testing. The osteoblasts extracted from the pups of rats that received 50 mg/kg caffeine during pregnancy exhibited increased expression of osteocalcin, osteopontin, sialoprotein, runx-2, alkaline phosphatase and type I collagen transcripts, resulting in increased synthesis of mineralization nodules. Neonates from rats treated with 50 mg/kg caffeine during pregnancy contained osteoblasts with a higher osteogenic potential characterized by increased expression of osteocalcin, osteopontin, sialoprotein, runx-2, alkaline phosphatase and type I collagen and increased synthesis of mineralization nodules.

  2. Differential expression of parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats. (United States)

    Kaalund, Sanne S; Riise, Jesper; Broberg, Brian V; Fabricius, Katrine; Karlsen, Anna S; Secher, Thomas; Plath, Niels; Pakkenberg, Bente


    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV(+) interneurons). In this study, we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical 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, but not in SI 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 phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations. © 2012 International Society for Neurochemistry.

  3. 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


    of parvalbumin-positive interneurons (PV(+) interneurons). In this study we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia, the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical......Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration...

  4. KCC2 expression changes in Diazepam-treated neonatal rats with hypoxia-ischaemia brain damage. (United States)

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


    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.

  5. Daily inhibition of postprandial hyperglycaemia with JTT-608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin-treated rats. (United States)

    Ohta, T; Sasase, T; Miyajima, K; Matsui, K; Matsushita, M; Furukawa, N; Yonemori, F


    Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.

  6. Proteomic identification of non-erythrocytic alpha-spectrin-1 down-regulation in the pre-optic area of neonatally estradiol-17β treated female adult rats. (United States)

    Govindaraj, Vijayakumar; Rao, Addicam Jagannadha


    It is well established that sexually dimorphic brain regions, which are critical for reproductive physiology and behavior, are organized by steroid hormones during the first 2 weeks after birth in the rodents. In our recent observation, neonatal exposure to estradiol-17β (E2) in the female rat revealed increase in cyclooxygenase 2 (COX-2) level, sexually dimorphic nucleus (SDN)-pre-optic area (POA) size and down-regulation of synaptogenesis related genes in POA in the adult stage. In the present study, using the same animal model, the protein profile of control and neonatally E2-treated POA was compared by 1D-SDS-PAGE, and the protein that shows a change in abundance was identified by LC-MS/MS analysis. Results indicated that there was a single protein band, which was down-regulation in E2-treated POA and it was identified as spectrin alpha chain, non-erythrocytic 1 (SPTAN1). Consistently, the down-regulation of SPTAN1 expression was also confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The SPTAN1 was identified as a cytoskeletal protein that is involved in stabilization of the plasma membrane and organizes intracellular organelles, and it has been implicated in cellular functions including DNA repair and cell cycle regulation. The evidence shows that any mutation in spectrins causes impairment of synaptogenesis and other neurological disorders. Also, protein-protein interaction analysis of SPTAN1 revealed a strong association with proteins such as kirrel, actinin, alpha 4 (ACTN4) and vinculin (VCL) which are implicated in sexual behavior, masculinization and defeminization. Our results indicate that SPTAN1 expression in the developing rat brain is sexually dimorphic, and we suggest that this gene may mediate E2-17β-induced masculinization and defeminization, and disrupted reproductive function in the adult stage.

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

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    Huang Yen


    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.

  8. Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water

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    Reyna Cristina Collí-Dulá


    Full Text Available Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others; animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3 and thyroxine (T4, were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.

  9. Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol (United States)

    Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.


    The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

  10. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)



    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2.

  11. 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


    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.

  12. Serum luteinizing hormone follicle-stimulating hormone and prolactin in neonatal-androgenized rats. (United States)

    Moguilevsky, J A; Scacchi, P; Dosoretz, D; Rubinstein, L


    Serum levels of LH, FSH, Prolactin and Testosterone of 90 days old male rats androgenized soon after birth were determined by specific radioimmunoassay and were compared to untreated rats. LH and FSH levels were also determined in 90 days old female rats neo-natally treated with testosterone and compared with normal diestrus rats. Androgenization of male rats significantly increased serum FSH and Prolactin levels without producing changes in plasma LH and testosterone concentrations. Similar increase in the FSH levels were found in androgenized female rats although plasma FSH concentrations were lower than in the male groups. These results obtained in male rats give an additional evidence that androgens acting in the first days of life are responsible of the higher levels of FSH and Prolactin that characterize the male or tonic pattern of gonadotrophin secretion.

  13. Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism

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    Dimitrios Angelis


    Full Text Available Maternal Graves’ disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves’ disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves’ disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves’ disease.

  14. Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion. (United States)

    Ogata, M; Noda, K; Akita, H; Ishibashi, H


    Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6-15min post formalin injection) and phase 2 (16-75min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I-II and V-VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of

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

    DEFF Research Database (Denmark)

    Martens, G A; Motté, E; Kramer, G


    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...

  16. Perinatal supplementation with omega-3 polyunsaturated fatty acids improves sevoflurane-induced neurodegeneration and memory impairment in neonatal rats.

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    Xi Lei

    Full Text Available OBJECTIVES: To investigate if perinatal Omega-3 polyunsaturated fatty acids (n-3 PUFAs supplementation can improve sevoflurane-induced neurotoxicity and cognitive impairment in neonatal rats. METHODS: Female Sprague-Dawley rats (n = 3 each group were treated with or without an n-3 PUFAs (fish oil enriched diet from the second day of pregnancy to 14 days after parturition. The offspring rats (P7 were treated with six hours sevoflurane administration (one group without sevoflurane/prenatal n-3 PUFAs supplement as control. The 5-bromodeoxyuridine (Brdu was injected intraperitoneally during and after sevoflurane anesthesia to assess dentate gyrus (DG progenitor proliferation. Brain tissues were harvested and subjected to Western blot and immunohistochemistry respectively. Morris water maze spatial reference memory, fear conditioning, and Morris water maze memory consolidation were tested at P35, P63 and P70 (n = 9, respectively. RESULTS: Six hours 3% sevoflurane administration increased the cleaved caspase-3 in the thalamus, parietal cortex but not hippocampus of neonatal rat brain. Sevoflurane anesthesia also decreased the neuronal precursor proliferation of DG in rat hippocampus. However, perinatal n-3 PUFAs supplement could decrease the cleaved caspase-3 in the cerebral cortex of neonatal rats, and mitigate the decrease in neuronal proliferation in their hippocampus. In neurobehavioral studies, compared with control and n-3 PUFAs supplement groups, we did not find significant spatial cognitive deficit and early long-term memory impairment in sevoflurane anesthetized neonatal rats at their adulthood. However, sevoflurane could impair the immediate fear response and working memory and short-term memory. And n-3 PUFAs could improve neurocognitive function in later life after neonatal sevoflurane exposure. CONCLUSION: Our study demonstrated that neonatal exposure to prolonged sevoflurane could impair the immediate fear response, working

  17. Effect of Costus igneus: The insulin plant, on prediabetes and diabetes in neonatal streptozotocin rats

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    Murthy EGK Talasila


    Full Text Available Introduction: Pre-diabetes is a condition that persists for a considerable duration before progressing into type 2 diabetes mellitus (T2DM. Development of resistance to insulin is the underlying cause of pre-diabetes, preventive measures such as diagnosis, treatment and exercise will preclude its development into T2DM. The present study aims at studying the effect of pre-treatment and post-treatment with isolated fraction of Costus igneus on pre-diabetes and diabetes in neonatal streptozotocin (STZ induced T2DM.Methods: Neonatal rats were treated with STZ and differentiated for pre-treatment and post-treatment. Rats of pre-treated group were treated with isolated fraction of Costus igneus (CIF from 4th week after STZ administration and after 12th week in non-treated rats of post-treatment group. The antihyperglycemic was studied on 7th and 12th week after STZ treatment using oral glucose tolerance test and the hypoglycemic effect was studied on day 1, 7, 14 and 21 of treatment after 12th week of STZ treatment in both pre and post treated groups.Results: Oral glucose tolerance test on 7th and 12th week had shown a protective effect against increase in blood glucose levels in pre-treated groups whereas, no such significant decrease was observed in non-treated groups. In the effect on hypoglycemia, a reduction in blood glucose levels was observed on treatment with CIF in both pre and post treated rats on 14th and 21st day.Conclusions: Treatment with CIF in pre-diabetic stage could reduce the chances of progression into T2DM and is also beneficial in diabetic rats, which could be due to increase in the peripheral utilization of glucose and the insulin mimetic effect of Costus igneus.

  18. Neonatal administration of citalopram delays somatic maturation in rats

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    T.C.B.J. Deiró


    Full Text Available We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5, 10 mg (Cit10 or 20 mg/kg (Cit20 citalopram sc, or saline (0.9% NaCl, w/v, sc. Compared to saline, body weight was lower (24.04%, P < 0.01 for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19%, P < 0.01. Tail length was reduced in the Cit20 group (15.48%, P < 0.001 from the 8th to the 21st day. A reduction in mediolateral head axis (10.53%, P < 0.05 was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16%, P < 0.001. A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28%, P < 0.05 from the 13th to the 21stday. Conversely, this axis showed accelerated growth from the 12th to the 21stday in the Cit5 group (13.05%, P < 0.05. Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

  19. Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin. (United States)

    Turk, Neslihan; Dağistanli, Fatma Kaya; Sacan, Ozlem; Yanardag, Refiye; Bolkent, Sema


    The aim of the study was to evaluate the effect of ghrelin treatment on obestatin, insulin gene expression and biochemical parameters in the pancreas of newborn-streptozocin (STZ) diabetic rats. Rats were divided into 4 groups. Group I: control rats treated with physiological saline; group II: control rats treated with 100 μg/kg/day ghrelin; group III: two days after birth rats that received 100mg/kg STZ injected as a single dose to induce neonatal diabetes; group IV: neonatal-STZ-diabetic rats treated with ghrelin for four weeks. Sections of the pancreas were examined with immunohistochemistry for the expression of obestatin and insulin and in situ hybridization for the expression of insulin mRNA. The blood glucose levels were measured. Tissue homogenates were used for protein, glutathione, lipid peroxidation and non-enzymatic glycosylation levels and antioxidant enzyme analysis. There was a significant difference in blood glucose levels in newborn-STZ-diabetic rats compared to ghrelin treated diabetic rats at weeks 1, 2 and 4. In group IV, pancreatic non-enzymatic glycosylation and lipid peroxidation levels were decreased, however, glutathione levels and enzymatic activities were increased. Insulin peptide and mRNA (+) signals in islets of Langerhans and obestatin immunopositive cell numbers showed an increase in group IV compared to group III. These results suggest that administration of ghrelin to newborn rats may prevent effects of diabetes. Copyright © 2011. Published by Elsevier GmbH.

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

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    Secher, Thomas; Berezin, Vladimir; Bock, Elisabeth


    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......The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities......, 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...

  1. Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

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    Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

    treated rats. microPET data revealed that DOM60 rats had a 40-47 % reduction in [11C]yohimbine binding in limbic and cortical brain regions relative to saline treated rats. We conclude that neonatal administration of DOM combined with the potential stress associated with behavioural testing results...... in a significant decrease in [11C]yohimbine binding in limbic and cortical brain regions. We suggest that the observed downregulation of α2 adrenoceptors is a result of elevated extracellular noradrenaline which may represent a form of preconditioning to decrease seizure susceptibility of the brain....

  2. The Physiologic Effects of Isoflurane, Sevoflurane, and Hypothermia Used for Anesthesia in Neonatal Rats (Rattus norvegicus). (United States)

    Huss, Monika K; Chum, Helen H; Chang, Angela G; Jampachairsi, Katechan; Pacharinsak, Cholawat


    Information regarding effective anesthetic regimens for neonatal rat pups is limited. Here we investigated whether isoflurane or sevoflurane anesthesia maintains physiologic parameters more consistently than does hypothermia anesthesia in neonatal rat pups. Rat pups (age, 4 d) were randomly assigned to receive isoflurane, sevoflurane, or hypothermia. Physiologic parameters monitored at 1, 5, 10, and 15 min included heart rate (HR), respiratory rate (RR), and oxygen saturation (%SpO2). Other parameters evaluated were loss and return of righting reflex, paw withdrawal reflex, and maternal acceptance. Corticosterone and glucose were sampled at 20 min and 24 h after anesthesia induction. Once a surgical plane of anesthesia was achieved, a skin incision was made on the right lateral thigh. After the procedure, all pups were accepted and cared for by their dam. Isoflurane- and sevoflurane-treated pups maintained higher HR, RR, %SpO2, and glucose levels than did hypothermia-treated pups. For both the isoflurane and sevoflurane groups, HR and RR were significantly lower at 10 and 15 min after anesthesia than at 1 min. Compared with hypothermia, isoflurane and sevoflurane anesthesia provided shorter times to loss of and return of the righting reflex. Although corticosterone did not differ among the groups, glucose levels were higher at 20 min after anesthesia induction than at 24 h in all anesthetic groups. We conclude that both isoflurane and sevoflurane anesthesia maintain physiologic parameters (HR, RR, %SpO2) more consistently than does hypothermia anesthesia in 4-d-old rat pups.

  3. Protective effect of polydatin on learning and memory impairments in neonatal rats with hypoxic‑ischemic brain injury by up‑regulating brain‑derived neurotrophic factor. (United States)

    Sun, Jin; Qu, Yunxia; He, Huiming; Fan, Xiaolei; Qin, Yuanhua; Mao, Weifeng; Xu, Lixin


    Polydatin is a key component of Polygonum cuspidatum, a herb with medical and nutritional value. The present study investigated the protective effect of polydatin against learning and memory impairment in neonatal rats with hypoxic‑ischemic brain injury (HIBI). The unilateral common carotid artery ligation method was used to generate neonatal HIBI rats. Y‑maze testing revealed that rats with HIBI exhibited memory impairment, while rats with HIBI treated with polydatin displayed enhanced long‑term learning and memory. Of note, polydatin was found to upregulate the expression of hippocampal brain‑derived neurotrophic factor (BDNF) in rats with HIBI. BDNF has a role in protecting HIBI‑induced brain tissue injury and alleviating memory impairment. These findings showed that polydatin had a protective effect against learning and memory impairment in neonatal rats with HIBI and that the protective effect may be mediated through the upregulation of BDNF.

  4. Neonatal handling induces anovulatory estrous cycles in rats

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    Gomes C.M.


    Full Text Available Since previous work has shown that stimulation early in life decreases sexual receptiveness as measured by the female lordosis quotient, we suggested that neonatal handling could affect the function of the hypothalamus-pituitary-gonadal axis. The effects of neonatal handling on the estrous cycle and ovulation were analyzed in adult rats. Two groups of animals were studied: intact (no manipulation, N = 10 and handled (N = 11. Pups were either handled daily for 1 min during the first 10 days of life or left undisturbed. At the age of 90 days, a vaginal smear was collected daily at 9:00 a.m. and analyzed for 29 days; at 9:00 a.m. on the day of estrus, animals were anesthetized with thiopental (40 mg/kg, ip, the ovaries were removed and the oviduct was dissected and squashed between 2 glass slides. The number of oocytes of both oviductal ampullae was counted under the microscope. The average numbers for each phase of the cycle (diestrus I, diestrus II, proestrus and estrus during the period analyzed were compared between the two groups. There were no significant differences between intact and handled females during any of the phases. However, the number of handled females that showed anovulatory cycles (8 out of 11 was significantly higher than in the intact group (none out of 10. Neonatal stimulation may affect not only the hypothalamus-pituitary-adrenal axis, as previously demonstrated, but also the hypothalamus-pituitary-gonadal axis in female rats.

  5. A new rat model of neonatal bilirubin encephalopathy (kernicterus). (United States)

    Amini, Naser; Vousooghi, Nasim; Soleimani, Mansoureh; Samadikuchaksaraei, Ali; Akbari, Mehdi; Safakheil, Hosein; Atafimanesh, Pezhman; Shahbazi, Ali; Brouki Milan, Peiman; Ramezani, Sara; Mozafari, Masoud; Joghataei, Mohammad Taghi

    Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively. The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs. This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Neonatal inhalatory anesthetic exposure: reproductive changes in male rats. (United States)

    Arena, A C; Pereira, O C M


    We investigated the effects of an inhalatory anesthetic (ethyl ether) during the neonatal period of brain sexual differentiation on the later fertility and sexual behavior of male rats. Animals were exposed to ethyl ether immediately after birth. At adulthood, body weight, testes wet weight, and plasma testosterone levels were not affected; however, neonatal exposure to ether showed alterations on male fertility: a decrease in the number of spermatids and spermatozoa, an increase in the transit time of cauda epididymal spermatozoa and a decrease in daily sperm production. An alteration of sexual behavior was also observed: decreased male sexual behavior and appearance of homosexual behavior when the male rats were castrated and pretreated with exogenous estrogen. Probably, the ether delayed or reduced the testosterone peak of the sexual differentiation period, altering the processes of masculinization and defeminization of the hypothalamus. Our results indicate that perinatal exposure to ethyl ether during the critical period of male brain sexual differentiation, acting as endocrine disruptors, has a long-term effect on the fertility and sexual behavior of male rats, suggesting endocrine disruption through incomplete masculinization and defeminization of the central nervous system.

  7. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

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


    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)

  8. Effects of hindlimb unloading on neuromuscular development of neonatal rats (United States)

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


    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.

  9. Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats


    Wang, Zhi; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi


    Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated by intranasal PDTC. Neurological outcome were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain...

  10. Significance of neonatal testicular sex steroids to defeminize anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats. (United States)

    Homma, Tamami; Sakakibara, Mototsugu; Yamada, Shunji; Kinoshita, Mika; Iwata, Kinuyo; Tomikawa, Junko; Kanazawa, Tetsuhiro; Matsui, Hisanori; Takatsu, Yoshihiro; Ohtaki, Tetsuya; Matsumoto, Hirokazu; Uenoyama, Yoshihisa; Maeda, Kei-Ichiro; Tsukamura, Hiroko


    The brain mechanism regulating gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release is sexually differentiated in rodents. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) have been suggested to be sexually dimorphic and involved in the GnRH/LH surge generation. The present study aimed to determine the significance of neonatal testicular androgen to defeminize AVPV kisspeptin expression and the GnRH/LH surge-generating system. To this end, we tested whether neonatal castration feminizes AVPV kisspeptin neurons and the LH surge-generating system in male rats and whether neonatal estradiol benzoate (EB) treatment suppresses the kisspeptin expression and the LH surge in female rats. Immunohistochemistry, in situ hybridization, and quantitative real-time RT-PCR were performed to investigate kisspeptin and Kiss1 mRNA expressions. Male rats were castrated immediately after birth, and females were treated with EB on postnatal Day 5. Neonatal castration caused an increase in AVPV kisspeptin expression at peptide and mRNA levels in the genetically male rats, and the animals showed surge-like LH release in the presence of the preovulatory level of estradiol (E2) at adulthood. On the other hand, neonatal EB treatment decreased the number of AVPV kisspeptin neurons and caused an absence of E2-induced LH surge in female rats. Semiquantitative RT-PCR analysis showed that neonatal steroidal manipulation affects Kiss1 expression but does not significantly affect gene expressions of neuropeptides (neurotensin and galanin) and enzymes or transporter for neurotransmitters (gamma-aminobutyric acid, glutamate, and dopamine) in the AVPV, suggesting that the manipulation specifically affects Kiss1 expressions. Taken together, our present results provide physiological evidence that neonatal testicular androgen causes the reduction of AVPV kisspeptin expression and failure of LH surge in genetically male rats. Thus, it is plausible that perinatal

  11. Glycolytic and Mitochondrial Metabolism in Pancreatic Islets from MSG-Treated Obese Rats Subjected to Swimming Training

    Directory of Open Access Journals (Sweden)

    Nayara de Carvalho Leite


    Full Text Available Backgrounds/Aims: Obese rats obtained by neonatal monosodium glutamate (MSG administration present insulin hypersecretion. The metabolic mechanism by which glucose catabolism is coupled to insulin secretion in the pancreatic β-cells from MSG-treated rats is understood. The purpose of this study was to evaluate glucose metabolism in pancreatic islets from MSG-treated rats subjected to swimming training. Methods: MSG-treated and control (CON rats swam for 30 minutes (3 times/week over a period of 10 weeks. Pancreatic islets were isolated and incubated with glucose in the presence of glycolytic or mitochondrial inhibitors. Results: Swimming training attenuated fat pad accumulation, avoiding changes in the plasma levels of lipids, glucose and insulin in MSG-treated rats. Adipocyte and islet hypertrophy observed in MSG-treated rats were attenuated by exercise. Pancreatic islets from MSG-treated obese rats also showed insulin hypersecretion, greater glucose transporter 2 (GLUT2 expression, increased glycolytic flux and reduced mitochondrial complex III activity. Conclusion: Swimming training attenuated islet hypertrophy and normalised GLUT2 expression, contributing to a reduction in the glucose responsiveness of pancreatic islets from MSG-treated rats without altering glycolytic flux. However, physical training increased the activity of mitochondrial complex III in pancreatic islets from MSG-treated rats without a subsequent increase in glucose-induced insulin secretion.

  12. [Protective effects of IGF-1 on cortical nerve cells of neonatal rats under oxidative stress]. (United States)

    Liu, Wei; Li, Wen-Bin; Chen, Zhi-Jun; Rong, Zhi-Hui; Chang, Li-Wen


    To investigate the protective effects of insulin-like growth factor-1 (IGF-1) on the nerve cells of neonatal rats under oxidative stress. Primary cortical neurons, oligodendrocytes, and astrocytes from newborn rats were cultured. An oxidative stress model was established with different concentrations of H2O2 (0-60 μmol/L); the degree of damage of nerve cells was evaluated by lactate dehydrogenase assay, and the viability of nerve cells was tested by MTT assay. An oxidative stress model was established with different concentration of H2O2 (0-80 μmol/L). Expression of Akt/p-Akt (Ser473) in neurons was measured by Western blot before and after IGF-1 (25 ng/mL) administration. Compared with those not treated with H2O2, the cortical neurons, oligodendrocytes, and astrocytes treated with different concentrations of H2O2 for 24 hours showed increased damage and decreased cell viability; compared with oligodendrocytes and astrocytes, neurons showed significantly more changes (P0.05); however, it had no significant effect on the inhibition of Akt phosphorylation by high-concentration H2O2, and the treated neurons still had a lower p-Akt level than untreated neurons (P0.05). Cortical neurons are more sensitive to oxidative stress induced by H2O2 than other nerve cells. IGF-1 has protective effects on cortical nerve cells under oxidative stress.

  13. Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats

    National Research Council Canada - National Science Library

    McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj; Phillips, Brian; Shen, Danny D; Juul, Sandra E


    The α2-adrenergic agonist dexmedetomidine (DEX) is increasingly used for prolonged sedation of critically ill neonates, but there are currently no data evaluating possible consequences of prolonged neonatal DEX exposure...

  14. The effect of HMGB1 on sub-toxic chlorpyrifos exposure-induced neuroinflammation in amygdala of neonatal rats. (United States)

    Tian, Jing; Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Li, Ying; Zhou, Jun; Zhao, Mingyi; Zhao, Mengwen; Zhang, Chen; Zhang, Yuxi; Wang, Peipei; Bing, Guoying; Zhao, Lingling


    Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5mg/kg CPF for 4 consecutive days (postnatal day 11-14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain. (United States)

    Boksa, Patricia; Zhang, Ying; Nouel, Dominique


    Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

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

    Directory of Open Access Journals (Sweden)

    Z Khaksar


    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.

  17. Imbalance in redox system of rat liver following permethrin treatment in adolescence and neonatal age. (United States)

    Gabbianelli, Rosita; Palan, Matyas; Flis, Damian Jozef; Fedeli, Donatella; Nasuti, Cinzia; Skarydova, Lucie; Ziolkowski, Wieslaw


    The effect of different permethrin treatments on the redox system of rat liver, is presented. Two types of oral administration were chosen: (i) sub-chronic treatment (1/10 of LD50 for 60 days) during adolescence (5 weeks old) and (ii) sub-acute treatment (1/44 of LD50 for 15 days) during early life (from postnatal days 6-21). The results show that adolescent permethrin treatment induces damage to the liver redox system, increasing lipid and protein peroxidation and reducing membrane fluidity in the hydrophilic--hydrophobic region of the bilayer. In addition, glutathione peroxidase (GPx) and GSH levels resulted decreased, while glutathione transferase (GST) and catalase (CAT) levels increased. The rats treated in early life with permethrin and sacrificed in adult age, showed less signs of damage compared to those exposed during adolescence in which lipid peroxidation was increased by 32%, whereas for the first group the raise was only 11%. Moreover, fluidity improved in the deeper hydrophobic membrane region of the treated group, while the level of CAT was significantly lower compared to the control one. Although sub-chronic treatment increased CAT and GST and decreased GPx and GSH levels, the present data suggest that a shorter exposure to permethrin during neonatal age decreased CAT level and it could represent an important risk factor for the onset of long-term liver damage.

  18. Long-term Follow-up of Children Treated with Neonatal Extracorporeal Membrane Oxygenation: neuropsychological outcome

    NARCIS (Netherlands)

    M.J. Madderom (Marlous)


    textabstractThis thesis aims to describe the long-term neuropsychological outcome of children and adolescents treated with neonatal extracorporeal membrane oxygenation (ECMO). ECMO is a pulmonary bypass technique providing temporary life support in potentially acute reversible (cardio)respiratory

  19. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat. (United States)

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


    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.

  20. Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation


    Vorst, Maria; Wildschut, Enno; Houmes, Robert Jan; Gischler, Saskia; Kist-Van Holthe, Joana; Burggraaf, Jacobus; Heijden, Bert; Tibboel, Dick


    textabstractIntroduction: Loop diuretics are the most frequently used diuretics in patients treated with extracorporeal membrane oxygenation (ECMO). In patients after cardiopulmonary bypass (CPB) surgery, the use of continuous furosemide infusion is increasingly documented. Because ECMO and CPB are 'comparable' procedures, continuous furosemide infusion is used in newborns on ECMO. We report on the use of continuous intravenous furosemide in neonates treated with ECMO. Methods: This was a ret...

  1. Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes (United States)

    Metzele, Roxana; Alt, Christopher; Bai, Xiaowen; Yan, Yasheng; Zhang, Zhi; Pan, Zhizhong; Coleman, Michael; Vykoukal, Jody; Song, Yao-Hua; Alt, Eckhard


    Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immunofluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory

  2. Effects of neonatal treatment with phytoestrogens, genistein and daidzein, on sex difference in female rat brain function: estrous cycle and lordosis. (United States)

    Kouki, Tom; Kishitake, Miki; Okamoto, Miho; Oosuka, Izumi; Takebe, Minoru; Yamanouchi, Korehito


    It is well known that neonatal exposure to estrogen induces masculinization or defeminization of the brain. In this study, the effects of neonatal treatment with two kinds of soybean isoflavone aglycone, genistein (GS) and daidzein (DZ), on the estrous cycle and lordosis behavior were investigated. Female rats were injected subcutaneously with 1 mg GS, 1 mg DZ, 100 microg estradiol (E2), or oil daily for 5 days from birth. As a result, vaginal opening was advanced in GS- or E2-treated females. A vaginal smear check indicated that oil- or DZ-treated females showed a constant 4- or 5-day estrous cycle, whereas GS- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovaries in the GS- or E2-treated groups were smaller than those in the oil- and DZ-treated groups and contained no corpora lutea. In the DZ group, although corpora lutea were seen, ovaries were smaller than that of control females. Behavioral tests were carried out after implantation of E2-tubes. All of the oil- or DZ-treated females showed lordosis with a high lordosis quotient (LQ). On the other hand, as male rats, LQs were extremely low in the E2-treated group, when compared to the oil-treated group. In the GS-treated group, the mean LQ was lower than that in the oil-treated group, but higher than those in the E2-treated female or male groups. These results suggest that genistein acts as an estrogen in the sexual differentiation of the brain and causes defeminization of the brain in regulating lordosis and the estrous cycle in rats. In addition, neonatal daidzein also has some influence on ovarian function.

  3. Early life triclocarban exposure during lactation affects neonate rat survival. (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; Chen, Jiangang


    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. © The Author(s) 2014.

  4. Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival (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


    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

  5. Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach. (United States)

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


    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

  6. Systemic compensatory response to neonatal estradiol exposure does not prevent depletion of the oocyte pool in the rat.

    Directory of Open Access Journals (Sweden)

    Clémentine Chalmey

    Full Text Available The formation of ovarian follicles is a finely tuned process that takes place within a narrow time-window in rodents. Multiple factors and pathways have been proposed to contribute to the mechanisms triggering this process but the role of endocrine factors, especially estrogens, remains elusive. It is currently hypothesized that removal from the maternal hormonal environment permits follicle formation at birth. However, experimentally-induced maintenance of high 17β-estradiol (E2 levels leads to subtle, distinct, immediate effects on follicle formation and oocyte survival depending on the species and dose. In this study, we examined the immediate effects of neonatal E2 exposure from post-natal day (PND 0 to PND2 on the whole organism and on ovarian follicle formation in rats. Measurements of plasma E2, estrone and their sulfate conjugates after E2 exposure showed that neonatal female rats rapidly acquire the capability to metabolize and clear excessive E2 levels. Concomitant modifications to the mRNA content of genes encoding selected E2 metabolism enzymes in the liver and the ovary in response to E2 exposure indicate that E2 may modify the neonatal maturation of these organs. In the liver, E2 treatment was associated with lower acquisition of the capability to metabolize E2. In the ovary, E2 depleted the oocyte pool in a dose dependent manner by PND3. In 10 µg/day E2-treated ovaries, apoptotic oocytes were observed in newly formed follicles in addition to areas of ovarian cord remodeling. At PND6, follicles without any visible oocyte were present and multi-oocyte follicles were not observed. Our study reveals a major species-difference. Indeed, neonatal exposure to E2 depletes the oocyte pool in the rat ovary, whereas in the mouse it is well known to increase oocyte survival.

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

    Directory of Open Access Journals (Sweden)

    J. Beltrand


    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.

  8. Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure. (United States)

    Hodyl, Nicolette A; Krivanek, Klara M; Clifton, Vicki L; Hodgson, Deborah M


    The efficacy of the neonatal innate immune system to respond to bacterial exposure following maternal infection is of great interest, as the neonatal period is one of relative immune immaturity, and is associated with high rates of morbidity and mortality. This study aimed to determine the response to an in-vivo endotoxin challenge in the neonatal period following prenatal exposure to bacterial endotoxin. Pregnant Fischer 344 dams received either endotoxin or the vehicle on gestational days 16, 18 and 20 (term=23 days). The neonatal (5 day) offspring were then exposed to an endotoxin challenge; blood was collected at baseline or at 4 h for analysis of blood cell counts, corticosterone, TNF alpha and IL-1 beta, levels. The neonatal rat pups responded to the challenge with significantly reduced corticosterone, TNF alpha and IL-1 beta levels compared to controls (p<0.003). Monocyte, neutrophil and eosinophil counts were also significantly reduced in the prenatal endotoxin offspring compared to controls (p<0.02). While the immune system is functionally immature in the neonatal period, these results suggest that prenatal infection may further reduce the capacity of the innate neonatal immune system to respond to endotoxin, leaving offspring more vulnerable to pathogenic invasion in neonatal life.

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

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    Ilvana Ziko


    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.

  10. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats. (United States)

    Koyuturk, Meral; Sacan, Ozlem; Karabulut, Sezin; Turk, Neslihan; Bolkent, Sehnaz; Yanardag, Refiye; Bolkent, Sema


    Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100 mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100 µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent. © 2015 International Federation for Cell Biology.

  11. An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation

    NARCIS (Netherlands)

    M.M.J. van der Vorst (Maria); J. den Hartigh (Jan); E.D. Wildschut (Enno); D. Tibboel (Dick); J. Burggraaf (Jacobus)


    textabstractIntroduction: The objective of the present study was to explore a continuous intravenous furosemide regimen that adapts to urine output in neonates treated with extracorporeal membrane oxygenation (ECMO). Methods: Seven neonates admitted to a paediatric surgical intensive care unit for

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

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    Soomaayeh Heysieat-talab


    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.

  13. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    Because cardiovascular disease remains a serious problem in modern human society, the aim of this study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD and LE rats when treated with myocardial ischemia and reperfusion operation. A 20-minute thoracotomy was performed ...

  14. Effects of neonatal 17α-ethinyloestradiol exposure on female-paced mating behaviour in the rat. (United States)

    Komine, Chiaki; Nakajima, Shingo; Kondo, Yasuhiko; Horii, Yasuyuki; Yoshida, Midori; Kawaguchi, Maiko


    Correct perinatal oestrogen levels are critical for sexual differentiation. For example, perinatal exposure to oestrogen causes masculinization and defeminization of the brain in female rats and also induces delayed effects after maturation characterized by early onset of abnormal oestrus cycling. However, the mechanisms underlying the above effects of oestrogen remain to be fully determined. 17α-ethinyloestradiol (EE), a common synthetic oestrogen widely used in oral contraceptives, binds specifically to oestrogen receptors. In this study, we demonstrated the effects of a single neonatal injection of high- or low-dose EE on reproductive behaviours. Female rats within 24 h after birth were subcutaneously injected with sesame oil, EE (0.02, 2 mg kg-1 ) and 17β-oestradiol (E2 ) (20 mg kg-1 ). Between 11 and 15 weeks of age, sexual behaviour was tested twice in a paced mating situation. Latency to enter, lordosis and soliciting behaviour were recorded. Both high-dose EE- and E2 -treated females showed a significantly lower lordosis quotient, decreased soliciting behaviours, increased rejection and fighting numbers. Accessibility to males was also delayed by neonatal E2 exposure, although it was shortened by high-dose EE exposure. In contrast, low-dose EE-treated females did not exhibit impaired sexual behaviour. These results suggest that single neonatal exposure to a high dose of EE or E2 disturbs the normal development of the female brain, resulting in impaired sexual behaviours in a female-paced mating situation. Besides, the differences noted between high-dose EE- and E2 -treated females might be caused by different affinities of the oestrogen receptors, metabolic rates or mechanisms of action. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. The Investigation of Garlic (Allium Sativum) Extract on Lead Detoxification of Neonatal Rats Kidney


    Habibollah Johari; Zahra Zamani; Mokhtar Mokhtari; Vahid Hemayatkhah Jahromi; Houshang Jamali; Mohammad Yazdani


     Background & Objectives: Lead as a naturally-occurring element has different effects on hematopoitic system, nervous system, kidney, reproductive system and bone. In this investigation, was determined the effect of garlic alcoholic-water extract in kidney poisoning treatment induced by lead in neonatal rat.Materials & Methods: Rats were divided into 7 groups of 8. The First group was the control group, which had received no materials. The second group had received 0/1...

  16. Hyperlipoproteinemia in streptozotocin-treated rats. (United States)

    Bar-On, H; Roheim, P S; Eder, H A


    In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal dose of streptozotocin was 45 mg/kg body weight for the sucrose-fed rats. With this dose, plasma glucose reached a maximum of over 600 mg/100 ml., and plasma insulin was reduced by 60 per cent. Plasma triglycerides rose in the sucrose-fed rats to over 1,000 mg/100 ml. two days after the streptozotocin was given and then decreased to over 770 mg./100 ml. 12 days after treatment and then to 585 mg./100 ml. 10 weeks after induction of diabetes. With this dose, ketonuria did not occur nor did any of the animals die, as occurred with higher doses. In the chow-fed rats, plasma triglyceride levels were elevated with the induction of diabetes to levels of approximately 300 mg./100 ml. The concentration of all the plasma lipoproteins increased with the induction of diabetes. The concentration of very-low density lipoprotein (VLDL) protein in the sucrose-fed diabetic increased fivefold, the low-density lipoprotein (LDL) protein increased, and especially striking was the increase in high-density lipoprotein (HDL) protein concentration, which became more pronounced with the duration of the diabetes. The diabetes produced by streptozotocin administration to sucrose-fed rats, thus, provides a useful model for the study of the hyperlipoproteinemia of diabetes.

  17. Neonatal Lipopolysaccharide Exposure Gender-Dependently Increases Heart Susceptibility to Ischemia/Reperfusion Injury in Male Rats. (United States)

    Zhang, Peng; Lv, Juanxiu; Li, Yong; Zhang, Lubo; Xiao, Daliao


    Background: Adverse stress exposure during the early neonatal period has been shown to cause aberrant development, resulting in an increased risk of adult disease. We tested the hypothesis that neonatal exposure to lipopolysaccharide (LPS) does not alter heart function at rest condition but causes heart dysfunction under stress stimulation later in life. Methods: Saline control or LPS were administered to neonatal rats via intraperitoneal injection. Experiments were conducted in 6 week-old male and female rats. Isolated hearts were perfused in a Langendorff preparation. Results: Neonatal LPS exposure exhibited no effects on the body weight of the developing rats, but induced decreases in the left ventricle (LV) to the body weight ratio in male rats. Neonatal LPS exposure showed no effects on the baseline heart function determined by in vivo and ex vivo experiments, but caused decreases in the post-ischemic recovery of the LV function in male but not female rats. Neonatal LPS-mediated LV dysfunction was associated with an increase in myocardial infarct size and the LDH release in the male rats. Conclusion: The present study provides novel evidence that neonatal immune challenges could induce gender-dependent long-term effects on cardiac development and heart function, which reinforces the notion that adverse stress exposure during the early neonatal period can aggravate heart functions and the development of a heart ischemia-sensitive phenotype later in life.

  18. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males (United States)

    Arendash, Gary W.; Gorski, Roger A.


    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.

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

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    Marco Sifringer


    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.

  20. 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


    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...

  1. Differential cytokine activity and morphology during wound healing in the neonatal and adult rat skin

    National Research Council Canada - National Science Library

    Wagner, W; Wehrmann, M


    .... Cytokines are known to play a key role in this process. The current study investigated the differential cytokine activity and healing morphology during healing of incisional skin wounds in rats of the ages neonatal (p0), 3 days old (p3...

  2. Distribution Dynamics of Recombinant Lactobacillus in the Gastrointestinal Tract of Neonatal Rats (United States)

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


    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

  3. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus (United States)

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


    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

  4. Antenatal betamethasone attenuates intrauterine infection-aggravated hyperoxia-induced lung injury in neonatal rats. (United States)

    Yoo, Hye Soo; Chang, Yun Sil; Kim, Jin Kyu; Ahn, So Yoon; Kim, Eun Sun; Sung, Dong Kyung; Jeon, Ga Won; Hwang, Jong Hee; Shim, Jae Won; Park, Won Soon


    Intrauterine infection can exacerbate postnatal hyperoxic lung injury. We hypothesized that antenatal betamethasone treatment attenuates hyperoxic lung injury aggravated by intrauterine infection in neonatal rats. Newborn Sprague-Dawley rats were divided into eight experimental groups according to (i) whether rats were exposed to normoxia (N) or hyperoxia (H, 85% oxygen) from postnatal day (P)1 to P14, (ii) whether antenatal betamethasone (0.2 mg/dose) or vehicle was administered to pregnant rats at gestation days (E)19 and E20, and (iii) whether intrauterine infection was induced or not antenatally. Intrauterine infection was induced by intracervical inoculation of Escherichia coli into pregnant rats on E19. We measured cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in P1 rat lungs and performed morphometric analyses and assessed inflammatory responses in lung tissue and bronchoalveolar lavage (BAL) at P14 by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and measurement of myeloperoxidase activity, collagen, and cytokine levels. Cytokine levels in P1 rat lungs were increased by intrauterine infection, and these increases were attenuated by antenatal betamethasone. Hyperoxic lung injuries, indicated by morphometric changes and an inflammatory response in the lung and BAL fluid, were aggravated by intrauterine infection at P14. This aggravation was significantly attenuated by antenatal betamethasone. Antenatal betamethasone attenuated aggravated hyperoxic lung injuries induced by intrauterine infection in neonatal rats via its anti-inflammatory actions.

  5. Pulmonary vascular responsiveness in rats following neonatal exposure to high altitude or carbon monoxide

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    Tucker, A.; Penney, D.G. (Colorado State Univ., Fort Collins, CO (United States) Wayne State Univ., Detroit, MI (United States))


    Exposure of adult and neonatal rats to high altitude increases pulmonary vascular responsiveness during the exposure. A study was undertaken to determine if a short exposure of neonatal rats to either high-altitude or carbon monoxide (CO) hypoxia would cause persistent alterations in pulmonary vascular responsiveness postexposure. One-day-old male Sprague-Dawley rats were obtained as 16 litters of 10-12 pups each. At 2 days of age, 4 litters were exposed to CO (500 ppm) for 32 days, and 4 litters were exposed to ambient air (AIR) in Detroit (200 m). Another 4 litters were exposed to 3500 m altitude (ALT) in a chamber for 32 days, and 3 litters were exposed to ambient conditions in Fort Collins (CON, 1524 m). After the exposures, all rats were maintained at 1524 m. At 2, 40, 76 and 112 days postexposure, lungs were isolated and perfused with Earle's salt solution (+Ficoll, 4 g%). Pulmonary vascular responsiveness was assessed by dose responses to angiotensin II (AII, 0.025-0.40 [mu]g) and acute hypoxia (3% O[sub 2] for 3 min). AII responses were higher in ALT vs CON rats at 2 and 40 days postexposure, but no differences were noted between CO and AIR rats. Baseline pulmonary vascular resistance and pulmonary arterial pressure (in isolated lungs) were higher in ALT rats at all four ages compared to the other three groups. Both the ALT and CO rats displayed hypertrophy of the right ventricle (RV) and the left ventricle (LV) at the termination of treatment and elevated hematocrit. LV hypertrophy and polycythemia regressed with time, but RV hypertrophy remained significant in the ALT rats through 112 days postexposure. The results indicate that neonatal exposure to ALT, but no CO, causes a persistent increase in pulmonary vascular responsiveness and RV hypertrophy for at least 112 days after termination of the exposure. 40 refs., 3 figs., 2 tabs.

  6. Effects of fetal brain grafting on adult behavioral masculinization and defeminization in neonatally androgenized female rats. (United States)

    Tsai, Y F; Chen, T J; Pi, W P; Tai, M Y; Huang, R L; Chiueh, C C; Peng, M T


    Treatment of neonatal female rats with androgen results not only in decreased female sexual behavior but also in enhanced male sexual behavior examined in adulthood. The effects of grafting fetal preoptic area (POA) neurons into the POA, and fetal hypothalamic (HPT) neurons into the ventromedial hypothalamus (VMH), were tested in neonatally androgen-sterilized rats (ASR). The rats were injected subcutaneously with 80 micrograms testosterone propionate within the 24 hours after birth to see if sexual behavior could be normalized by fetal brain grafts. In repeated tests on ASR grafted with fetal HPT into the VMH, the lordotic response was seen to increase to the level seen in non-ASR controls, while the increase in mounting behavior in ASR was suppressed following grafting of fetal POA or cerebral cortex into the POA. These results suggest that there are dysfunctions of POA and VMH in ASR, and that the dysfunctions revealed by sexual behavior can be overcome by fetal POA or HPT grafting.

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

    Directory of Open Access Journals (Sweden)

    Torres P.M.M.


    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.

  8. The Nature of the Sensory Input to the Neonatal Rat Barrel Cortex. (United States)

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


    Sensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. This early sensory input may involve: (1) stimulation arising from passive interactions with the mother and littermates and (2) sensory feedback arising from spontaneous infant movements. The relative contributions of these mechanisms under natural conditions remain largely unknown, however. Here, we show that, in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate, with comparable efficiency, in driving cortical activity. Both tactile signals arising from the littermate's movements under conditions simulating the littermates' position in the litter, and spontaneous whisker movements efficiently triggered bursts of activity in barrel cortex. Yet, whisker movements with touch were more efficient than free movements. Comparison of the various experimental conditions mimicking the natural environment showed that tactile signals arising from the whisker movements with touch and stimulation by the littermates, support: (1) a twofold higher level of cortical activity than in the isolated animal, and (2) a threefold higher level of activity than in the deafferented animal after the infraorbital nerve cut. Together, these results indicate that endogenous (self-generated movements) and exogenous (stimulation by the littermates) mechanisms cooperate in driving cortical activity in newborn rats and point to the importance of the environment in shaping cortical activity during the neonatal period. Sensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. However, the origins of sensory input to the neonatal somatosensory cortex in the natural environment remain largely unknown. Here, we show that in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate

  9. Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy.

    Directory of Open Access Journals (Sweden)

    Fang Lei

    Full Text Available It has been postulated that prenatal cigarette smoke exposure (CSE increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8 and CSE (n = 8. Experiments were performed on neonatal (0-3days rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF and integrated amplitude (IA of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4, no significant difference was detected between the two groups in either BF or IA (P>0.05. Under condition of perfusing with acidified aCSF (pH 7.0, BF was increased and IA was decreased in both groups (P<0.01. However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and -22.38 ± 2.51% vs. -44.90 ± 3.92% for IA (P<0.01. In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates.

  10. Neonatal Intracranial Aneurysm Rupture Treated by Endovascular Management: A Case Report

    Directory of Open Access Journals (Sweden)

    Yi-Pei Tai


    Full Text Available Pediatric intracranial aneurysm rupture is rare, and is traditionally managed by surgical clipping. To the best of our knowledge, endovascular embolization of aneurysms in neonates has not previously been reported in Taiwan. We report a 9-day-old boy with intracranial aneurysms who underwent endovascular embolization, representing the youngest reported case in Taiwan. The 9-day-old boy presented with non-specific symptoms of irritable crying, seizure and respiratory distress. Computed tomography disclosed intraventricular hemorrhage, subarachnoid hemorrhage and focal intracranial hemorrhage around the right cerebellum. Subsequent computed tomographic angiography showed two sequential fusiform aneurysms, measuring 3 mm, located in the right side posterior inferior cerebellar artery (PICA. The patient underwent endovascular embolization because of the high risk of aneurysm re-rupture and the impossibility of surgical clipping due to the fusiform nature of the aneurysms. A postembolization angiogram revealed complete obliteration of the right distal PICA and proximal aneurysm. The distal PICA aneurysm was revascularized from the collateral circulation, but demonstrated a slow and delayed filling pattern. The patient's condition remained stable over the following week, and he was discharged without anticonvulsant therapy. No significant developmental delay was noted at follow-up at when he was 3 months old. This case emphasizes the need for clinical practitioners to consider a diagnosis of intracranial hemorrhage in neonates with seizure and increased intracranial pressure. Neonatal intracranial aneurysms can be treated safely by endovascular treatment.

  11. Reproductive activities of female albino rats treated with quassin, a ...

    African Journals Online (AJOL)

    Groups V, VI and VII rats were also treated orally with 0.1 mg/kg, 1.0mg/kg and 2.0 mg/kg body weight of quassin for 60 days but were left untreated for another 30 days, to serve as the recovery groups. At the end of each experimental period, blood samples were collected from each rat. Fertility study was done by cohabiting ...

  12. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation


    Chaloner, A.; Rao, A; Al-Chaer, E.D.; MEERVELD, B. GREENWOOD-VAN


    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liqui...

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

    Directory of Open Access Journals (Sweden)

    Dubner Ronald


    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

  14. Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect. (United States)

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


    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.

  15. Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

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    Villarim Neto, Arthur; Acucena, Maria Kadja Meneses Torres; Pereira, Kercia Regina Santos Gomes; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Postgraduate Program in Health Sciences; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. of Surgery; Bernardo-Filho, Mario [State University of Rio de Janeiro, RJ (Brazil). Dept. of Biophysics and Biometry


    Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1 ml of samarium-153-EDTMP via orbital plexus (25 {mu} Ci. After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI / g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the ninth day after the administration of the second chemotherapy cycle, the rats had a significant weight loss (314.50 +- 22.09 g) compared (p<0.5) to pre-treatment weight (353.66 {+-} 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study. (author)

  16. Hesperidin pretreatment protects hypoxia-ischemic brain injury in neonatal rat. (United States)

    Rong, Z; Pan, R; Xu, Y; Zhang, C; Cao, Y; Liu, D


    Neonatal hypoxia-ischemic encephalopathy (HIE) remains a major cause of brain damage, leading to high disability and mortality rates in neonates. In vitro studies have shown that hesperidin, a flavanone glycoside found abundantly in citrus fruits, acts as an antioxidant. Although hesperidin has been considered as a potential treatment for HIE, its effects have not been fully evaluated. In this study, the protective effect of hesperidin pretreatment against hypoxia-ischemic (HI) brain injury and possible signal pathways were investigated using in vivo and in vitro models. In vivo HI model employed unilateral carotid ligation in postnatal day 7 rat with exposure to 8% hypoxia for 2.5h, whereas in vitro model employed primary cortical neurons of neonatal rats subjected to oxygen and glucose deprivation for 2.5h. Hesperidin pretreatment significantly reduced HI-induced brain tissue loss and improved neurological outcomes as shown in 2,3,5-triphenyltetrazolium chloride monohydrate staining and foot-fault results. The neuroprotective effects of hesperidin are likely the results of preventing an increase in intracellular reactive oxygen species and lipid peroxide levels. Hesperidin treatment also activated a key survival signaling kinase, Akt, and suppressed the P-FoxO3 level. Hesperidin pretreatment protected neonatal HIE by reducing free radicals and activating phosphorylated Akt. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Hass, M.A.; Massaro, D.


    The failure of adult rats to survive prolonged exposure to > 95% O/sub 2/ is generally ascribed to the inability of their lungs to increase antioxidant enzyme synthesis in response to the oxidant challenge. The authors studied the synthesis rate of the antioxidant enzyme CuZn superoxide dismutase (CuZn SOD) in lungs of adult and neonatal rats exposed to conditions that alter the lung's oxidant-to-oxidant balance. Lung CuZn SOD synthesis in the adult was significantly increased after 24 h of hyperoxia but fell to control levels after further exposure, whereas in neonatal lungs an increased rate of synthesis of CuZn SOD was found only after 72 h or hyperoxia. The adult lung responded to two in vitro oxidant stresses, (diethyldithiocarbamate exposure and heat (42/degrees/C)) with increases in CuZn SOD synthesis twice the magnitude of those in the neonatal lung. These data indicate that the adult lung is at least as capable as the neonatal lung of increasing its synthesis of CuZn SOD in response to an oxidative stress. However, the inability of the adult lung to maintain an increased rate of CuZn SOD synthesis during in vivo hyperoxia may contribute to the poor tolerance of the adult lung to > 95% O/sub 2/.

  18. Neonatal monosodium glutamate treatment modifies glutamic acid decarboxylase activity during rat brain postnatal development. (United States)

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


    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.

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


    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.

  20. Antidiabetic activity of Pseudarthria viscida aqueous root extract in neonatal streptozotocin-induced NIDDM rats

    Directory of Open Access Journals (Sweden)

    Rajendran Kuppusamy


    Full Text Available The antidiabetic activity of the aqueous root extract of Pseudarthria viscida (L. Wight & Arn., Fabaceae, was investigated in normal and neonatal streptozotocin (n2-STZ-induced non insulin-dependent diabetes mellitus (NIDDM rats and compared with glibenclamide as a reference standard. Two different doses (250 and 500 mg/kg of the extract were administered to normal and experimental diabetic rats for 21 days. Fasting blood glucose levels, serum lipid profiles and changes in body weight were evaluated in normal and diabetic rats while serum insulin, glycated hemoglobin, urea, creatinine, magnesium, protein, albumin and glycogen, glutamate oxaloacetate transaminase (GOT, glutamate pyruvate transaminase (GPT, lactate dehydrogenase (LDH levels in kidney and liver were evaluated additionally in diabetic rats. Treatment with extract at both dose levels was found to exhibit antidiabetic activity, with the higher dose showing more significant activity.

  1. Antidiabetic activity of Pseudarthria viscida aqueous root extract in neonatal streptozotocin-induced NIDDM rats

    Directory of Open Access Journals (Sweden)

    Rajendran Kuppusamy


    Full Text Available The antidiabetic activity of the aqueous root extract of Pseudarthria viscida (L. Wight & Arn., Fabaceae, was investigated in normal and neonatal streptozotocin (n2-STZ-induced non insulin-dependent diabetes mellitus (NIDDM rats and compared with glibenclamide as a reference standard. Two different doses (250 and 500 mg/kg of the extract were administered to normal and experimental diabetic rats for 21 days. Fasting blood glucose levels, serum lipid profiles and changes in body weight were evaluated in normal and diabetic rats while serum insulin, glycated hemoglobin, urea, creatinine, magnesium, protein, albumin and glycogen, glutamate oxaloacetate transaminase (GOT, glutamate pyruvate transaminase (GPT, lactate dehydrogenase (LDH levels in kidney and liver were evaluated additionally in diabetic rats. Treatment with extract at both dose levels was found to exhibit antidiabetic activity, with the higher dose showing more significant activity.

  2. Administration of a leptin antagonist during the neonatal leptin surge induces alterations in the redox and inflammatory state in peripubertal /adolescent rats. (United States)

    Mela, Virginia; Hernandez, Oskarina; Hunsche, Caroline; Diaz, Francisca; Chowen, Julie A; De la Fuente, Mónica


    The importance of the neonatal leptin surge in rodents in neurodevelopmental processes has aroused curiosity in its implication in other physiological systems. Given the role of leptin in neuro-immune interactions, we hypothesized that the neonatal leptin surge could have an effect on the oxidative and inflammatory stress situations of both systems. We blocked the neonatal leptin surge by a leptin antagonist and measured several parameters of oxidative and inflammatory stress in the spleen, hypothalamus and adipose tissue of peripubertal/adolescent rats. The treated rats showed lower activity of several antioxidant enzymes in the spleen and their leukocytes released lower levels of mitogen-stimulated IL-10 and IL-13 and higher levels of TNF-alpha. In conclusion, the neonatal leptin surge may have a key role in the establishment of adequate redox and inflammatory states in the immune system, which is important for the generation of adequate immune responses and to obtain and maintain good health. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

    Directory of Open Access Journals (Sweden)

    Lominiki Slawo


    Full Text Available Abstract Background Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM. The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs, in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. Methods Neonatal rats (7-days of age were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP, non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. Results Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. Conclusions Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.

  4. The role of oxidative stress in high glucose-induced apoptosis in neonatal rat cardiomyocytes. (United States)

    Zhou, Xiang; Lu, Xiang


    Accumulating evidence has demonstrated that apoptosis plays a critical role in the pathogenesis of diabetic cardiomyopathy. However, the exact molecular mechanisms by which hyperglycaemia induces cardiomyocyte apoptosis are not fully understood. The present study was designed to investigate the role of oxidative stress in high glucose-induced apoptosis in cultured neonatal rat cardiomyocytes. The MTT assay was used to detect the viability of cardiomyocytes exposed to different concentrations of glucose. Oxidative stress was evaluated by measuring intracellular reactive oxygen species with 2',7'-dichlorofluoresce diacetate staining and by detecting malondialdehyde and superoxide dismutase in the supernatant of culture media. Cardiomyocyte apoptosis was determined by flow cytometry and confocal laser scanning microscopy with Annexin V/PI staining. Our results showed that high glucose can induce oxidative stress and promote apoptosis in neonatal rat cardiomyocytes and the antioxidant can protect against high glucose-induced apoptosis, which suggests that oxidative stress is involved in high glucose-induced cardiomyocyte apoptosis. Furthermore, caspase-3 was found to be activated in the process of high glucose-induced oxidative stress, which subsequently contributes to increased apoptosis in neonatal rat cardiomyocytes. In conclusion, our study demonstrates that oxidative stress is involved in high glucose-induced cardiomyocyte apoptosis via activation of caspase-3.

  5. Prevention of red cell lysis in artesunate-treated rats: A role for ...

    African Journals Online (AJOL)

    -phosphate dehydrogenase activity in male rats. Twelve (12) male rats were divided into two groups of six (6) rats each. Group 1 rats were control rats which received normal saline while group 2 rats were treated with artesunate orally for five ...

  6. Effect of G-CSF and TPO on HIBD in neonatal rats. (United States)

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


    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.

  7. Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats? (United States)

    Ommati, M M; Tanideh, N; Rezakhaniha, B; Wang, J; Sabouri, S; Vahedi, M; Dormanesh, B; Koohi Hosseinabadi, O; Rahmanifar, F; Moosapour, S; Akhlaghi, A; Heidari, R; Zamiri, M J


    With increasing knowledge that the immune system has a major impact on reproductive ‎health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress ‎has been revealed. This study addresses the impact of neonatal thymectomy on male ‎reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80 days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices ‎‎in blood and spermatozoa were highest in fully thymectomized, intermediate ‎in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and ‎testosterone, and mitochondrial adenosine triphosphate and ‎dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, ‎intermediate in partially thymectomized, and highest in both pubertal and mature control rats.‎ The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role

  8. Effect of pregnancy on cadmium-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Takizama, Y. (Akita Univ. School of Medicine, Japan); Nakamura, I.; Kurayama, R.; Hirasawa, F.; Kawai, K.


    It is well known that itai-itai disease with the osteopathy is broken out among multiparas, 40 years of age and up Japanese residents. In this paper we described an experimental study of effect of pregnancy on cadmium treated rats. Female mature rats were administered drinking water containing 50 and 200 ppm cadmium as CdCl/sub 2/. During 180 days of the experiment, three times of pregnancy were succesful, though slight depression of body weight gain was noticed in the 200 ppm group. The cadmium was accumulated in the kidneys, liver and bone proportionally to the amount of cadmium administered. No significant change was recognized in serum calcium, phosphorus and alkaline phosphatase levels after 180 days. Though cadmium 200 ppm treated rats showed slight histological lesions in the proximal convoluted tubules of the kidney, there appeared to be no osteomalacia including excess formation of osteoid tissue.

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

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


    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. The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

    Directory of Open Access Journals (Sweden)

    Menshanov Petr N.


    Full Text Available In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking.

  11. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    Directory of Open Access Journals (Sweden)

    Yong-Hong Yi


    Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

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

    NARCIS (Netherlands)

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


    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

  13. Asthma-like airway inflammation and responses in a rat model of atopic dermatitis induced by neonatal capsaicin treatment

    Directory of Open Access Journals (Sweden)

    Han RT


    . Airway responsiveness was measured in terms of airway resistance and compliance using the flexiVent system. In the capsaicin-treated rats, persistent dermatitis developed, and scratching behaviors increased over several weeks. The levels of IgE in the serum and BAL fluid as well as the mRNA expression of Th2 cytokines, including IL-4, IL-5, and IL-13, in both the skin and the lungs were elevated, and the number of eosinophils in the BAL fluid was also increased in the capsaicin-treated rats compared to control rats. Morphological analysis of the airway revealed smooth muscle hypertrophy and extensive mucus plug in the capsaicin-treated rats. Functional studies demonstrated an increment of the airway resistance and a decrement of lung compliance in the capsaicin-treated rats compared to control rats. Taken together, our findings suggested that neonatal capsaicin treatment induced asthma-like airway inflammation and responses in juvenile rats. Keywords: atopic march, scratching, cytokines, eosinophils, BAL fluid, pruritus, flexiVent, airway hypertrophy and remodelling 

  14. 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


    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.

  15. Equipotent subanesthetic concentrations of sevoflurane and xenon preventing cold-stimulated vocalization of neonatal rats. (United States)

    Gill, Hannah; Thoresen, Marianne; Bishop, Sarah; Smit, Elisa; Liu, Xun; Walloe, Lars; Dingley, John


    The effects of inhaled anesthetics on the developing brain are studied using neonatal rodents exposed to fractions of minimum alveolar concentration (to avoid cardiorespiratory compromise). However, these fractions cannot be assumed to be equipotent. Xenon's anesthetic and neuroprotective properties warrant investigation in these models. Therefore, equipotent, subanesthetic concentrations of inhaled anesthetics are needed. Forty-eight Wistar rats (Charles River Laboratories, Kent, United Kingdom) on postnatal day 9 were randomized to eight concentrations of inhaled anesthetics: isoflurane, sevoflurane, or xenon. Exposure was closely monitored in individual metal-based chambers resting on a 35°C mat to maintain normothermia. A 25°C mat was used to stimulate vocalization and a sound recording made (1 min, 1 to 100 kHz). Rectal temperature or partial pressure of carbon dioxide and pH of mixed arteriovenous blood were measured immediately after the exposure. Concentration-response models were constructed using logistic regression (dependent variable: vocalization and explanatory variable: concentration). The effects of all other explanatory variables were assessed by inserting them individually into the model. The effective inhaled concentrations preventing cold-stimulated vocalization in 50 and 95% of neonatal rats (EiC50 and EiC95) on postnatal day 9 were 0.46 and 0.89% sevoflurane and 20.15 and 34.81% xenon, respectively. The effect on the EiC50 of all other explanatory variables, including duration, was minimal. Stability of EiC50 isoflurane was not achieved over three durations (40, 80, and 120 min exposure). Partial pressure of carbon dioxide and pH in mixed arteriovenous blood appeared normal. The authors report equipotent subanesthetic concentrations of sevoflurane and xenon in neonatal rats with preserved cardiopulmonary function. This may be useful in designing neonatal rodent models of anesthesia.

  16. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. (United States)

    Liu, Xun; Jary, Sally; Cowan, Frances; Thoresen, Marianne


    To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age. From 2006-2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs. Brain magnetic resonance imaging (MRI) was assessed using a 0-11 severity score. Postneonatal seizures, epilepsy rates, and AED treatments were documented. One hundred thirty-four survivors were assessed at 18-24 months; adverse outcome was defined as death or Bayley III composite Cognition/Language or Motor scores <85 and/or severe cerebral palsy or severely reduced vision/hearing. Epilepsy rates in 103 children age 4-8 years were also documented. aEEG confirmed seizures occurred precooling in 77 (57%) 151 of neonates; 48% had seizures during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18-24 months, one third of infants had an adverse outcome including 11% mortality. At 2 years, 8 (6%) infants had an epilepsy diagnosis (ILAE definition), of whom 3 (2%) received AEDs. Of the 103 4- to 8-year-olds, 14 (13%) had developed epilepsy, with 7 (7%) receiving AEDs. Infants/children on AEDs had higher MRI scores than those not on AEDs (median [interquartile range] 9 [8-11] vs. 2 [0-4]) and poorer outcomes. Nine (64%) of 14 children with epilepsy had cerebral palsy compared to 13 (11%) of 120 without epilepsy, and 10 (71%) of 14 children with epilepsy had adverse outcomes versus 23 (19%) of 120 survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity precooling, and MRI scores predicted childhood epilepsy. We report, in a regional cohort of infants cooled for perinatal asphyxia, 6% with epilepsy at 2 years (2% on AEDs

  17. Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of 'schizophrenia-like' behaviour in the rat. (United States)

    Gaskin, Philip L R; Alexander, Stephen P H; Fone, Kevin C F


    Schizophrenia is a debilitating disorder comprising positive, negative and cognitive deficits with a poorly defined neurobiological aetiology; therefore, animal models with greater translational reliability are essential to develop improved therapies. This study combines two developmental challenges in rats, neonatal phencyclidine (PCP) injection and subsequent rearing in social isolation from weaning, to attempt to produce more robust behavioural deficits with greater translational relevance to schizophrenia than either challenge alone. Forty-two male Lister-hooded rat pups received the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP, 10 mg/kg, s.c.), or vehicle on post-natal day (PND) 7, 9 and 11 and were weaned on PND 23 into group housing (saline-treated n = 11 or PCP-treated n = 10) or isolation (saline n = 10 or PCP n = 11). Six weeks post-weaning, novelty- and PCP-induced (3.2 mg/kg) locomotor activity, novel object discrimination, prepulse inhibition of acoustic startle and contextual memory in a conditioned emotion response (CER) were recorded. Isolation rearing alone significantly elevated baseline locomotor activity and induced visual recognition memory impairment in novel object discrimination. Neonatal PCP treatment did not induce locomotor sensitisation to a subsequent acute PCP injection, but it impaired prepulse inhibition when combined with isolation rearing. CER freezing behaviour was significantly reduced by isolation rearing but an even greater effect occurred when combined with neonatal PCP treatment. Neonatal PCP and isolation rearing both produce behavioural deficits in adult rats, but combined treatment caused a wider range of more severe cognitive impairments, providing a more comprehensive preclinical model to determine the neurobiological aetiology of schizophrenia than either treatment alone.

  18. Effect of growth hormone on growth and myelination in the neonatal hypothyroid rat. (United States)

    King, R A; Smith, R M; Meller, D J; Dahlenburg, G W; Lineham, J D


    The possible involvement of a deficit of GH and insulin-like growth factor-I (somatomedin C) (IGF-I/SMC) in mediating the effects of propylthiouracil (PTU)-induced hypothyroidism on body and skeletal growth and myelination was studied in the neonatal rat. Myelination (as assessed by 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity), skeletal growth (as assessed by tail length) and body weight of pups from PTU-treated mothers were significantly retarded compared with normal animals or euthyroid controls. At 20 days after birth, plasma GH in hypothyroid animals was undetectable (less than 10 micrograms/l), pituitary GH content was 1.2% of control, and plasma, liver and kidney IGF-I/SMC concentrations were 63, 68 and 50% of control values respectively. CNP activity in hypothyroid brain was 52% of normal controls but the concentration of IGF-I/SMC was 113-154% of control. Treatment of hypothyroid animals from day 1 with GH (10 mg/kg body weight per day) restored liver and plasma IGF-I/SMC concentrations at 20 days to values above those of normal animals and euthyroid controls. The concentration of IGF-I/SMC was also significantly (P less than 0.001) restored in hypothyroid kidney (79% of normal), but the concentration in brain was unaffected. These observations provide evidence that the GH treatment employed in the present experiments was adequate to restore the deficit. GH treatment had no significant effect on tail length or CNP activity, and only a small (4-24%) effect on body weight at 20 days. Only thyroxine was able fully to restore body weight and substantially restore tail length and CNP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 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


    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......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...... only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO...

  20. Diffusion tensor imaging correlates with cytopathology in a rat model of neonatal hydrocephalus

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    Hertzler Dean A


    Full Text Available Abstract Background Diffusion tensor imaging (DTI is a non-invasive MRI technique that has been used to quantify CNS abnormalities in various pathologic conditions. This study was designed to quantify the anisotropic diffusion properties in the brain of neonatal rats with hydrocephalus (HCP and to investigate association between DTI measurements and cytopathology. Methods DTI data were acquired between postnatal day 7 (P7 and P12 in 12 rats with HCP induced at P2 and in 15 age-matched controls. Animals were euthanized at P11 or P22/P23 and brains were processed with immunohistochemistry for glial fibrillary acidic protein (GFAP, ionized calcium-binding adaptor molecule (Iba-1, and luxol fast blue (LFB to assess astrocytosis, microglial reactivity and degree of myelination, respectively. Results Hydrocephalic rats were consistently found to have an abnormally low (at corrected p-level of Conclusions This study demonstrates the feasibility of employing DTI on the brain in experimental hydrocephalus in neonatal rats and reveals impairments in multiple regions of interest in both grey and white matter. A strong correlation was found between the immunohistochemical results and the changes in anisotropic diffusion properties.

  1. Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

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    Peter Kiss


    Full Text Available 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.

  2. Effects of neonatal overfeeding on juvenile and adult feeding and energy expenditure in the rat.

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    Aneta Stefanidis

    Full Text Available Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanism(s underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL compared with those from control litters (CL. There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males had reduced brown adipose tissue (BAT temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages.

  3. Effects of neonatal overfeeding on juvenile and adult feeding and energy expenditure in the rat. (United States)

    Stefanidis, Aneta; Spencer, Sarah J


    Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanism(s) underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL) compared with those from control litters (CL). There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active) phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males) had reduced brown adipose tissue (BAT) temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages.

  4. Increased concentrations of 3-hydroxykynurenine in vitamin B6 deficient neonatal rat brain. (United States)

    Guilarte, T R; Wagner, H N


    Increased concentrations of the endogenous tryptophan metabolite 3-hydroxykynurenine (3-HK) were measured in the brains of vitamin B6 deficient neonatal rats. Mean concentrations of 3-HK in B6 deficient cerebellum, corpus striatum, frontal cortex, and pons/medulla ranged from 9.7 to 18.6 and 102 to 142 nmol/g of wet tissue at 14 and 18 days of age, respectively. 3-HK was not significantly increased in control neonatal or adult rat brain, vitamin B6 deficient rat brain at 7 days of age, or in brains from adult rats deprived of vitamin B6 for 58 days. The administration of daily intraperitoneal injections of vitamin B6 from the 14th to the 18th day of age decreased the concentration of 3-HK to control levels. 3-HK has been shown by other investigators to produce seizures when injected into the cerebral ventricles of adult rodents. Thus, our studies show the accumulation in brain of a putative endogenous convulsant as the result of a nutritional deficiency.

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

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    Laura Louise Scott


    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.

  6. Early walking in the neonatal rat: a kinematic study. (United States)

    Jamon, M; Clarac, F


    The development of the early stage of locomotion (between Postnatal Days 3 and 10) was studied in newborn rats. At this age, rats are known to perform limited locomotor activities, consisting of an inefficient nonpostural gait termed crawling. By providing appropriate olfactory stimulation, it was possible to override the pups' reluctance to walk and to discover their actual locomotor abilities. The step period decreased from 1,200 ms to 900 ms from Postnatal Days 4 to 9, showing both a regular decrease in the swing and a discontinuous decrease in the stance phase. The fore- and hindlimb periods stabilized early on an alternate pattern of coupling. The ipsilateral coupling shifted progressively from 220 degrees to 260 degrees in relation with the change in the gait pattern. In parallel with the change in timing, the newborn rats showed gradual changes in the foot position and in the interlimb spatial coordination. These results show that quadruped locomotion develops before postural control is acquired, in a continuous process as the nervous system develops.

  7. Biomechanical properties of bones from rats treated with sevelamer. (United States)

    Draca, Natasa; Tikvica, Ana; Eljuga, Domagoj; Semenski, Damir; Brncić, Mladen; Vukicević, Slobodan


    Sevelamer hydrochloride is used for ten years in patients on dialysis as a phosphate binder. We have previously shown that oral application of sevelamer prevents the bone loss and increases the bone volume in ovariectomized rats. In this study we further analysed the biomechanical properties of bones from rats treated with sevelamer utilizing a threepoint bending test to determine the mechanical properties of the cortical bone of the mid-shaft femur, while the indentation test was used to determine the mechanical properties of cancellous bone in the marrow cavity of the distal femoral metaphysis. Parameters analyzed included: maximum load (F(u)), stiffness (S), energy absorbed (W), toughness (T) and ultimate strength (sigma). The intrinsic properties, stress, elastic modulus and toughness were determined from measured maximum load, strains, stiffness, energy absorbed, outer and inner diameters, and calculated bone cross-sectional moment of inertia. Sevelamer was given to rats for 25 weeks with a content of 3% of sevelamer in a standard diet, starting immediately following ovariectomy (OVX). Animals were divided to the following groups: (1) Sham; (2) Sham + sevelamer 3%; (3) OVX; (4) OVX + sevelamer 3%. Our results showed that sevelamer particularly influenced the rat trabecular bone by increasing the maximum load for 26.2%, energy absorbed for 24.2% and the ultimate strength for 26.2% in sham animals treated with sevelamer 3%, as compared to sham rats. Sevelamer 3% in OVX rats also increased the maximum load for 71.4%, stiffness for 70.7%, energy absorbed for 55.9% and the ultimate strength for 71.3% as compared to OVX controls. In the three bending test sevelamer had a very little effect on preventing loss of bone strenght in the cortical bone. These results collectively suggest that sevelamer improves bone biomechanical properties, mainly affecting trabecular bone quality in both normal and ovariectomized rats.

  8. The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development (United States)

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


    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

  9. Lower trunk of brachial plexus injury in the neonate rat: effects of timing repair. (United States)

    Lauretti, Liverana; Pallini, Roberto; Romani, Rossana; Di Rocco, Federico; Ciampini, Alessandro; Gangitano, Carlo; Del Fa, Aurora; Fernandez, Eduardo


    After lesion of a peripheral nerve in neonatal mammals, motoneurons undergo a cell death. We wanted to ascertain if early surgery could influence such post-axotomy motoneuronal death and improve the functional outcome. In this study, we investigated the functional and anatomical results after immediate and delayed repair of the lower trunk of brachial plexus (BP) sectioned at birth in rats. In neonate rats, the lower trunk of the left BP was cut. This nerve trunk was repaired either immediately [immediately-reconstructed group of rats (IR), or 30 days after, tardy reconstructed group of rats (TR)]; in the third group of animals, the nerve was not repaired (noreconstructed group of rats, NoR). In each group of animals, functional studies were performed at 90 days of age using the grooming test and the walking tracks analysis. Histologic studies of the C7-T1 spinal cord and lower trunk of BP were performed at 30 and 90 days of age; the numbers of motoneuron and axon were counted. Functional recovery was related to the difference in motoneuron number between the injured and the uninjured sides of the spinal cord of the operated animals. On the one side, only in the rats in which the inferior trunk was immediately repaired, the difference in motoneuron number between the two sides of the spinal cord was not statistically significant; these animals showed a good axonal regeneration and function recovery. On the other side, in the rats in which the inferior trunk was left unrepaired or tardy repaired, the decrease in motoneuron number in the injured side compared with the uninjured side of the spinal cord was statistically significant; these animals showed no axonal regeneration and no function recovery. The results cited above suggest that an important role in restoration of good neurological function after section of the lower trunk of BP in neonate rats is played by early nerve repair. Good neurological function was related more to a quite numerical balance of

  10. Effects of dehydroepiandrosterone in rats injected with streptozotocin during the neonatal period. (United States)

    Giroix, M H; Malaisse-Lagae, F; Portha, B; Sener, A; Malaisse, W J


    Control rats and diabetic animals injected with streptozotocin during the neonatal period were either maintained on a standard diet or given access to food supplemented with dehydroepiandrosterone (DHEA, 0.2%) for 11 days before sacrifice. In both control and diabetic rats, DHEA feeding augmented the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase and cytosolic NADP-linked malate dehydrogenase in liver, but not so in either the parotid gland or pancreatic islets. DHEA lowered, in both control and diabetic rats, the ratio between D-glucose oxidation and utilization and the rate of insulin release in pancreatic islets exposed to a high concentration of D-glucose, as well as the insulin concentration and insulin/glucose ratio in plasma. These findings support the view that, in diabetes, DHEA, by increasing sensitivity to insulin, may allow islet B-cells to avoid the otherwise unfavorable consequences of chronic hyperactivity.

  11. Dependence of normal development of skeletal muscle in neonatal rats on load bearing (United States)

    Ohira, Y.; Tanaka, T.; Yoshinaga, T.; Kawano, F.; Nomura, T.; Nonaka, I.; Allen, D. L.; Roy, R. R.; Edgerton, V. R.


    Antigravity function plays an important role in determining the morphological and physiological properties of the neuromuscular system. Inhibition of the normal development of the neuromuscular system is induced by hindlimb unloading during the neonatal period in rats. However, the role of gravitational loading on the development of skeletal muscle in rats is not well understood. It could be hypothesized that during the early postnatal period, i.e. when minimal weight-supporting activity occurs, the activity imposed by gravity would be of little consequence in directing the normal development of the skeletal musculature. We have addressed this issue by limiting the amount of postnatal weight-support activity of the hindlimbs of rats during the lactation period. We have focused on the development of three characteristics of the muscle fibers, i.e. size, myonuclear number and myosin heavy chain expression.

  12. Feminine dimension in the play fighting of rats (Rattus norvegicus) and its defeminization neonatally by androgens. (United States)

    Pellis, S M; Pellis, V C; McKenna, M M


    In rats (Rattus norvegicus), juvenile males engage in more play fighting (a male-typical behavior) than do juvenile females, and this difference is based on perinatal influences of androgens. We show that there are qualitative and quantitative differences between the sexes in the type of defensive responses and their manner of execution. In defensive responses rats try to avoid having their napes contacted by the partner's snout. The sex differences arise from females' greater response distance; that is, females responded to an approach when the partner's snout was further from the nape. This permits females to use different defensive responses and to use them more successfully. This greater response distance is defeminized by the neonatal administration of testosterone propionate. Our findings suggest that play fighting in rats has both male- and female-typical features and that these are, at least in part, influenced perinatally by androgens.




    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

  14. The effect of neonatal immune challenge on reproduction by altering intraovarian kisspeptin/GPR54 system in the rat. (United States)

    Wang, Bin-Qiao; Chen, Yuan-Yuan; Lan, Xiao-Xiao; Zhou, Zhi-Yang; Xu, Xin-Xin; Wu, Xue-Qing


    Immune challenge in early life has been observed to influence the long-term reproductive dysfunction. On PNDs 3 and 5, female offsprings were administered with LPS (50μg/kg, i.p.) or saline. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 56-70 days. At 10 weeks of age, the ovaries were removed for immunostaining and RNA analysis. Neonatal exposure to LPS resulted in a significant delay puberty onset as well as destroyed expression of ovulation related genes. At PND 42 and 70, a significant increase in Kiss1 mRNA and Kisspeptin expression was detected at proestrus and oestrus in neo-LPS treated rats compared with the counterparts. Therefore, neonatal LPS exposure had a long-term effect on reproductive function and the up-regulated expression of ovarian Kiss1 and kisspeptin during the ovulatory transition stage may contribute to ovulatory dysfunction induced by peripheral LPS administration in early life. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    Yuan Chia-Yi


    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.

  16. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.


    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

  17. Dietary choline during periadolescence attenuates cognitive damage caused by neonatal maternal separation in male rats. (United States)

    Moreno Gudiño, Hayarelis; Carías Picón, Diamela; de Brugada Sauras, Isabel


    Choline (Ch) is an essential nutrient that acts as a cognitive facilitator when administered during perinatal periods, and it has been recognised as a 'pharmacological' agent that can ease cognitive dysfunctions provoked by exposure to damaging stimuli during early developmental stages. The aim of the present work is to determine whether providing a diet rich in Ch would reduce the severity of the memory deficit provoked by a neonatal stress episode in male adult rats. The effect of Ch on memory was measured using memory tasks such as object and place recognition. Ontogenetic manipulations were conducted during two sensitive developmental periods. During the first post-natal (PN) 14 days, only the male rat pups were selected and half of them were separated from the mother, group maternal separation (MS). Subsequently, during periadolescence (PN 21-60), the rats were exposed to a deficient (DEF = 0 g/kg Ch chloride), sufficient (CON = 1.1 g/kg Ch chloride), or supplemented (SUP = 5 g/kg Ch chloride) diets for this nutrient. The results indicated that for group MS, only rats fed with the SUP diet were able to recognise the familiar object and place that had been experienced 24 hours before, unlike groups DEF and CON. In addition, whereas rats in the non-separated group (No-MS) recognised the object independently of the diet, only rats that received a DEF diet failed to recognise the place, showing that a Ch deficit affects spatial memory tasks. These results show that Ch supplementation during periadolescence can attenuate the memory deficit provoked by extended neonatal stress.

  18. Rooming-In to Treat Neonatal Abstinence Syndrome: Improved Family-Centered Care at Lower Cost. (United States)

    Holmes, Alison Volpe; Atwood, Emily C; Whalen, Bonny; Beliveau, Johanna; Jarvis, J Dean; Matulis, John C; Ralston, Shawn L


    The incidence and associated costs of neonatal abstinence syndrome (NAS) have recently risen sharply; newborns with NAS occupy 4% of NICU beds. We implemented a coordinated program for NAS including standardized protocols for scoring, medications and weaning, and a calm rooming-in environment, to improve family-centered care and to decrease both length of stay (LOS) and hospital costs. In early 2013, a multidisciplinary quality improvement team began consecutive plan-do-study-act (PDSA) cycles. We trained nurses in modified Finnegan scoring, ensured scoring only after on-demand feeds during skin-to-skin care, and standardized physician score interpretation. We provided prenatal family education, increased family involvement in symptom monitoring and nonpharmacologic treatment, and treated otherwise healthy infants on the inpatient pediatric unit instead of in the NICU. We measured outcomes using statistical process control methods. At baseline, 46% of inborn infants at-risk for NAS were treated with morphine; by 2015, this decreased to 27%. Adjunctive use of phenobarbital decreased from 13% to 2% in the same period. Average LOS for morphine-treated newborns decreased from 16.9 to 12.3 days, average hospital costs per treated infant decreased from $19 737 to $8755, and costs per at-risk infant dropped from $11 000 to $5300. Cumulative morphine dose decreased from 13.7 to 6.6 mg per treated newborn. There were no adverse events, and 30-day readmission rates remained stable. A coordinated, standardized NAS program safely reduced pharmacologic therapy, LOS, and hospital costs. Rooming-in with family and decreased use of NICU beds were central to achieved outcomes. Copyright © 2016 by the American Academy of Pediatrics.

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

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    Taghizadeh R


    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

  20. Precipitated and conditioned withdrawal in morphine-treated rats. (United States)

    Becker, Ginger L; Gerak, Lisa R; Li, Jun-Xu; Koek, Wouter; France, Charles P


    Stimuli that are paired with opioid withdrawal can themselves produce effects similar to withdrawal that might promote relapse. This study compared precipitated and conditioned withdrawal and tested whether withdrawal is modified by clonidine or morphine. Morphine-treated rats (10 mg/kg/12 h) received naloxone (3.2 mg/kg) in a novel environment (conditioned stimuli [CS]). Other rats received naloxone in the absence of the CS. Body weight and observable signs were used to measure withdrawal. Naloxone produced weight loss and withdrawal signs in morphine-treated rats. Following pairings of the CS and naloxone, the CS alone had effects similar to naloxone; conditioned withdrawal was greater after three naloxone/CS pairings, as compared to one, and with longer morphine treatment. Antagonist-precipitated withdrawal was greater in rats that previously were physically dependent on morphine, as compared to withdrawal in rats that were never dependent; however, conditioned withdrawal did not differ between groups. When administered concurrently with naloxone, clonidine (0.1 mg/kg) attenuated some precipitated withdrawal signs, although conditioned withdrawal was largely unchanged. Administration of 10 mg/kg of morphine before the CS alone attenuated all conditioned withdrawal signs, whereas 0.1 mg/kg of clonidine before the CS alone reduced some directly observable signs and not weight loss. Conditioned withdrawal occurs rapidly and is greater with longer periods of morphine treatment or more pairings of naloxone and the CS; however, a history of physical dependence does not increase conditioned withdrawal. Modification of conditioned withdrawal by drugs might be a useful approach for treating relapse.

  1. Frankincense improves memory retrieval in rats treated with Lipopolysaccharide

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    Beheshti Siamak


    Full Text Available Introduction: Frankincense has been shown to possess anti-inf lammatory activity. In this studythe effect of pretreatment with the hydro-alcoholic extract of frankincense on memory retrievalwas assessed in lipopolysaccharide (LPS treated rats.Methods: Forty-two adult male Wistar rats were distributed into 7 groups of 6 each. One groupreceived LPS (1 mg/kg; i.p pre-test. The control group received saline (1 ml/kg; i.p. 2 groups ofanimals received frankincense (50 mg/kg; P.O or DMSO 5% (1 ml/kg; P.O and 30 minutes laterLPS (1 mg/kg; i.p. Two other groups of animals received frankincense (50 mg/kg; P.O or DMSO5% (1 ml/kg; P.O and 30 minutes later saline (1 ml/kg; i.p. Another group of rats received LPS(1 mg/kg; i.p and 30 minutes later Ibuprofen (100 mg/kg; P.O. In all the experimental groups,memory retrieval was assessed 4 hours following the last injection, using a passive avoidancetask (PAT. Hippocampal TNF-α levels were measured by ELISA as an index of LPS-inducedneuroinf lammation.Results: LPS impaired memory retrieval by decreasing step-through latency (STL, significantly.LPS also increased levels of TNF-α in the hippocampus as compared to the control group.Administration of frankincense (50 mg/kg; P.O before LPS (1 mg/kg; i.p improved memoryretrieval as compared to the control group. Frankincense reduced hippocampal TNF-α level in theLPS treated rats, significantly, compared to the control group.Conclusion: The results indicate that the hydro-alcoholic extract of frankincense has the potentialto improve memory retrieval in LPS treated rats, possibly via an anti-neuroinf lammatory activity.

  2. Unusual localization and translocation of TRPV4 protein in cultured ventricular myocytes of the neonatal rat

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    Y. Zhao


    Full Text Available TRPV4 protein forms a Ca2+-permeable channel that is sensitive to osmotic and mechanical stimuli and responds to warm temperatures, and expresses widely in various kinds of tissues. As for cardiac myocytes, TRPV4 has been detected only at the mRNA level and there were few reports about subcellular localization of the protein. The purpose of the present study was to investigate the expression profile of TRPV4 protein in cultured neonatal rat ventricular myocytes. Using Western blots, immunofluorescence, confocal microscopy and immuno-electron microscopy, we have shown that TRPV4 protein was predominantly located in the nucleus of cultured neonatal myocytes. Furthermore, cardiac myocytes responded to hypotonic stimulation by translocating TRPV4 protein out of the nucleus. The significance and mechanism concerning the unusual distribution and translocation of TRPV4 protein in cardiac myocytes remain to be clarified.

  3. Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats. (United States)

    Lazzaretti, Camilla; Kincheski, Grasielle Clotildes; Pandolfo, Pablo; Krolow, Rachel; Toniazzo, Ana Paula; Arcego, Danusa Mar; Couto-Pereira, Natividade de Sá; Zeidán-Chuliá, Fares; Galvalisi, Martin; Costa, Gustavo; Scorza, Cecilia; Souza, Tadeu Mello E; Dalmaz, Carla


    Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.

  4. Serotonin 2A receptor mRNA levels in the neonatal dopamine-depleted rat striatum remain upregulated following suppression of serotonin hyperinnervation. (United States)

    Basura, G J; Walker, P D


    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.

  5. Inhaled nitric oxide improves lung structure and pulmonary hypertension in a model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats. (United States)

    Tourneux, Pierre; Markham, Neil; Seedorf, Gregory; Balasubramaniam, Vivek; Abman, Steven H


    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.

  6. Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat. (United States)

    Wolf, Rainer; Dobrowolny, Henrik; Nullmeier, Sven; Bogerts, Bernhard; Schwegler, Herbert


    The role of the thalamus in schizophrenia has increasingly been studied in recent years. Deficits in the ventral thalamus have been described in only few postmortem and neuroimaging studies. We utilised our previously introduced neurodevelopmental animal model, the neonatal excitotoxic lesion of the ventral thalamus of Sprague-Dawley rats (Wolf et al., Pharmacopsychiatry 43:99-109, 22). At postnatal day (PD7), male pubs received bilateral thalamic infusions with ibotenic acid (IBA) or artificial cerebrospinal fluid (control). In adulthood, social interaction of two animals not familiar to each other was studied by a computerised video tracking system. This study displays clear lesion effects on social interaction of adult male rats. The significant reduction of total contact time and the significant increase in distance between the animals in the IBA group compared to controls can be interpreted as social withdrawal modelling a negative symptom of schizophrenia. The significant increase of total distance travelled in the IBA group can be hypothesised as agitation modelling a positive symptom of schizophrenia. Using a triple concept of social interaction, the percentage of no social interaction (Non-SI%) was significantly larger, and inversely, the percentage of passive social interaction (SI-passive%) was significantly smaller in the IBA group when compared to controls. In conclusion, on the background of findings in schizophrenic patients, the effects of neonatal ventral thalamic IBA lesions in adult male rats support the hypothesis of face and construct validity as animal model of schizophrenia.

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

  8. The Effects of Hydro-Alcoholic Extract of Zingiber Officinale on Prevention from Plumbism in Kidney Tissue of Neonatal Rats

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    Habiballah Johari


    Full Text Available Background: In the present research, the effects of hydro-alcoholic extract of Zingiber officinale (ginger on treating lead-poisoned kidney of neonatal rats was studied.Materials and Methods: This research was conducted as a laboratory work. The neonatal rats were divided into 7 groups of 10 samples. The first control group received no treatment. The second control group received 0.1 mg of distilled water. As an experimental group, the one received an amount of 0.6 g/l lead. The fourth group received only 2 g/kg body weight of hydro-alcoholic extract of ginger. Groups 5 to 7 each initially received 0.6 g/l lead and then amounts of 0.5, 1 and 2 g/kg hydro-alcoholic extract of ginger. The injections were administered via oral gavage during 10 consecutive days.Results: According to the obtained results, the body and kidney weights showed a significant reduction in experimental groups that had received amounts of 1 and 2 g/kg in comparison with the group that had received lead. The kidney weight of the group that had received only extract showed no significant difference in comparison with the control group. As for the body weights, however, it showed a significant increase. Moreover, the body and kidney weights of the lead-injected group showed a significant increase in comparison with the control group.Conclusion: Lead can cause damage to kidney tissues. Due to its antioxidant and protective effect, ginger can be a medication to nephrotoxicity of lead and prevent kidney tissues from destruction.

  9. Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups. (United States)

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


    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.

  10. Neonatal Exposure to Low-Dose (1.2%) Sevoflurane Increases Rats' Hippocampal Neurogenesis and Synaptic Plasticity in Later Life. (United States)

    Chen, Xi; Zhou, Xue; Yang, Lu; Miao, Xu; Lu, Di-Han; Yang, Xiao-Yu; Zhou, Zhi-Bin; Kang, Wen-Bin; Chen, Ke-Yu; Zhou, Li-Hua; Feng, Xia


    The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h. On P35-40, rats' hippocampus-dependent learning and memory was tested using the Morris water maze. Cognition-related and synapse-related proteins in the hippocampus were measured using Western blotting on P35. On the same day, neurogenesis and synapse ultrastructure were evaluated using immunofluorescence and transmission electron microscopy (TEM). On P35, the rats neonatally exposed to 1.2% sevoflurane showed better behavioral results than control rats, but not in the 2.4% sevo group. Exposure to 1.2% sevoflurane increased the number of 5'-bromo-2-deoxyuridine (BrdU)-positive cells in the dentate gyrus and improved both synaptic number and ultrastructure in the hippocampus. The expression levels of BDNF, TrkB, postsynaptic density (PSD)-95, and synaptophysin in the hippocampus were also increased in the 1.2% sevo group. In contrast, no significant changes in neurogenesis or synaptic plasticity were observed between the C group and the 2.4% sevo group on P35. These results showed that exposure of the developing brain to a low concentration of sevoflurane for 6 h could promote spatial learning and memory function, along with increased hippocampal neurogenesis and synaptic plasticity, in later life.

  11. Organ explant culture of neonatal rat ventricles: a new model to study gene and cell therapy.

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    A Dénise den Haan

    Full Text Available Testing cardiac gene and cell therapies in vitro requires a tissue substrate that survives for several days in culture while maintaining its physiological properties. The purpose of this study was to test whether culture of intact cardiac tissue of neonatal rat ventricles (organ explant culture may be used as a model to study gene and cell therapy. We compared (immuno histology and electrophysiology of organ explant cultures to both freshly isolated neonatal rat ventricular tissue and monolayers. (Immuno histologic studies showed that organ explant cultures retained their fiber orientation, and that expression patterns of α-actinin, connexin-43, and α-smooth muscle actin did not change during culture. Intracellular voltage recordings showed that spontaneous beating was rare in organ explant cultures (20% and freshly isolated tissue (17%, but common (82% in monolayers. Accordingly, resting membrane potential was -83.9±4.4 mV in organ explant cultures, -80.5±3.5 mV in freshly isolated tissue, and -60.9±4.3 mV in monolayers. Conduction velocity, measured by optical mapping, was 18.2±1.0 cm/s in organ explant cultures, 18.0±1.2 cm/s in freshly isolated tissue, and 24.3±0.7 cm/s in monolayers. We found no differences in action potential duration (APD between organ explant cultures and freshly isolated tissue, while APD of monolayers was prolonged (APD at 70% repolarization 88.8±7.8, 79.1±2.9, and 134.0±4.5 ms, respectively. Organ explant cultures and freshly isolated tissue could be paced up to frequencies within the normal range for neonatal rat (CL 150 ms, while monolayers could not. Successful lentiviral (LV transduction was shown via Egfp gene transfer. Co-culture of organ explant cultures with spontaneously beating cardiomyocytes increased the occurrence of spontaneous beating activity of organ explant cultures to 86%. We conclude that organ explant cultures of neonatal rat ventricle are structurally and electrophysiologically similar

  12. Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord

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    Kiehn, O; Sillar, K T; Kjaerulff, O


    We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5-50 microM) elicited either no measurable root...... activity, or activity of a highly variable nature. When present, the NA-induced activity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony between antagonistic motor pools. Finally, in a few cases, NA induced a slow...

  13. Whole cell voltage clamp recordings from cultured neurons of the supraoptic area of neonatal rat hypothalamus. (United States)

    Cobbett, P; Mason, W T


    Whole-cell voltage and current clamp recordings were made from cultured neurons from the hypothalamic supraoptic area of neonatal rats. These neurons fired spontaneous Na+-action potentials, appearing as mixed Na+/K+-currents in voltage clamp. Isolated Na+-currents (less than 3 nA) were rapidly activated and inactivated during positive potential pulses from -80 mV. Two voltage-activated Ba2+-currents (less than 1 nA) were also recorded. These techniques offer a promising new approach for studying the striking electrical behavior of cultured hypothalamic neurons.

  14. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation. (United States)

    Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B


    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

  15. Neonatal hyperthyroidism on rat heart: interrelation with nitric oxide and sex. (United States)

    Rodríguez, L; Detomaso, F; Braga, P; Prendes, M; Perosi, F; Cernadas, G; Balaszczuk, A; Fellet, A


    To clarify the mechanism mediating the effect of hyperthyroidism on cardiac function during the second month of life in rats. Male and female Sprague-Dawley rats were assigned to a control or to a triiodothyronine (T3)-treated group. Treatment of each group was started on the third day after birth. Control rats (Eut) received 0.9 NaCl [0.1 ml/100 g body weight (BW)] every second day during 60 days and T3-treated rats (Hyper) received subcutaneous (SC) T3 injections every second day during 60 days. Hyperthyroidism decreased left ventricle volume only in male rats. Female euthyroid rats presented higher atrial nitric oxide synthase (NOS) activity than male rats and hormonal treatment decreased this enzyme's activity in both sexes. Euthyroid male and female rats had similar atrial NOS protein levels, but females had higher caveolin (cav) 3 protein levels. T3 treatment increased this protein only in males. Female rats had lower ventricular NOS activity than male rats; hyperthyroidism increased NOS activity in both sexes but this effect was associated with lower cav 3 protein levels. Hyperthyroidism did not change cav 1 protein levels in both male and female rats. The results of this study demonstrating clinically relevant sex-related differences in the pathophysiology of the hyperthyroid heart have raised new questions regarding the mechanisms responsible for the observed differences. This study suggests that sex-related intrinsic factors such as nitric oxide may modulate the response to hyperthyroidism that leads to cardiovascular dysfunction.

  16. Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study. (United States)

    Koning, Sarah H; Hoogenberg, Klaas; Scheuneman, Kirsten A; Baas, Mick G; Korteweg, Fleurisca J; Sollie, Krystyna M; Schering, Bertine J; van Loon, Aren J; Wolffenbuttel, Bruce H R; van den Berg, Paul P; Lutgers, Helen L


    To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment - diet-only versus additional insulin therapy - were based on the 2010 national Dutch guidelines. Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens -diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population. A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p = obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

  17. Enhanced nicotinic acetylcholine receptor-mediated [3H]norepinephrine release from neonatal rat hypothalamus. (United States)

    O'Leary, K T; Leslie, F M


    Nicotinic acetylcholine receptor (nAChR)-evoked release of norepinephrine (NE) has been demonstrated in a number of brain regions that receive sole noradrenergic innervation from the locus coeruleus (LC). Many of these structures display enhanced nicotine-stimulated NE release in the neonate. We have examined the hypothalamus in order to determine if this region, which receives NE projections from both the LC and medullary catecholaminergic nuclei, also demonstrates maturational changes in nAChR-mediated NE release. Quantification of radiolabeled-NE release from rat hypothalamus slices by a maximally effective dose of nicotine revealed a peak response during the first postnatal week. This was followed by a decrease at postnatal day (P) 14, and a second peak at P21. Thereafter, release was equivalent to that observed at P14. Comparison of the pharmacological properties of nAChRs mediating NE release in neonatal (P7) and mature hypothalamus suggested involvement of different nAChR subtypes at the two ages. Using the selective toxin, DSP-4, nAChR-mediated NE release in the neonatal hypothalamus was shown to be from LC terminals. Our findings demonstrate an early sensitivity of hypothalamic LC terminals to nAChR regulation that may be associated with development of systems controlling critical homeostatic functions such as stress, feeding and cardiovascular regulation.

  18. Retrospective cohort study comparing neonatal outcomes of women treated with glyburide or insulin in gestational diabetes: a 5-year experience in a South Indian teaching hospital. (United States)

    Mathews, Jiji Elizabeth; Biswas, Biwas; Samuel, Prasanna; Jana, Atanu Kumar; Muliyil, Jaya Prakash; Mathai, Matthews


    To assess the effectiveness of glyburide in preventing complications of gestational diabetes in neonates as compared to insulin. Information from birth register, maternal and neonatal records were obtained. Five hundred and seventy-seven gestational diabetics with moderate hyperglycemia i.e., with highest fasting plasma glucose value of ≤130 mg/dl and/or highest post-prandial value of ≤250 mg/dl treated with insulin or glyburide were included from a cohort of 769 women needing additional therapy to initial diet therapy during a 5-year period. Thus neonatal outcomes of 303 women treated with insulin and 274 women treated with glyburide were compared. Baseline plasma glucose levels in the group treated with insulin were higher. The mean birth weight (SD) of the neonates in women treated with insulin was 3021.3 g (604.19) as compared to 3104.6 g (499.35, P = 0.07) in the group treated with glyburide. Neonatal outcomes such as hypoglycemia (4.9%, 3.6%, P = 0.44), hypocalcemia (1.3%, 0.7%, P = 0.48), polycythemia (1.7%, 0.7%, P = 0.31), macrosomia (11.6%, 8.7%, P = 0.26), congenital anomalies (2.1%, 2.3%, P = 0.87), birth trauma (1.4%, 1.2%, P = 0.79) were similar in both groups. Neonates of women treated with insulin were more likely to have hyperbilirubinemia (11.5%, 6.5%, P = 0.03). Neonatal outcomes of women treated with glyburide were comparable to those in women treated with insulin. More number of neonates of mothers treated with insulin had hyperbilirubinemia compared to neonates of mothers treated with glyburide (11.5%, 6.5% P = 0.03).

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

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    Guy eSandner


    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.

  20. Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats.

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    Hemmen Sabir

    Full Text Available Therapeutic hypothermia (TH is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI in seven-day-old (P7 rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI.120 P7 rat pups underwent a severe HI insult; unilateral carotid artery ligation followed by hypoxia (8% O2 for 150min at experimental normothermia (NT-37: Trectal 37°C. Surviving pups were randomised to immediate NT-37 for 5h (n = 36, immediate TH-32: Trectal 32°C for 5h (n = 25 or immediate TH-32 plus 50% inhaled Xe for 5h (n = 24. Pups were sacrificed after one week of survival. Relative area loss of the ligated hemisphere was measured, and neurons in the subventricular zone of this injured hemisphere were counted, to quantify brain damage.Following the HI insult, median (interquartile range, IQR hemispheric brain area loss was similar in all groups: 63.5% (55.5-75.0 for NT-37 group, 65.0% (57.0-65.0 for TH-32 group, and 66.5% (59.0-72.0 for TH-32+Xe50% group (not significant. Correspondingly, there was no difference in neuronal cell count (NeuN marker in the subventricular zone across the three treatment groups.Immediate therapeutic hypothermia with or without additional 50% inhaled Xe, does not provide neuroprotection one week after severe HI brain injury in the P7 neonatal rat. This model aims to mimic the clinical situation in severely asphyxiated neonates and treatment these newborns remains an ongoing challenge.

  1. Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats (United States)

    Breese, G.R.; Hulebak, K.L.; Napier, T.C.; Baumeister, A.; Frye, G.; Mueller, R.A.


    Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR. PMID:3104958

  2. Method for Estimating Bilirubin Isomerization Efficiency in Phototherapy to Treat Neonatal Jaundice (United States)

    Lisenko, S. A.; Kugeiko, M. M.


    We propose a method for quantitative assessment of the efficacy of phototherapy to treat neonatal jaundice using the diffuse reflectance spectrum for the newborn's skin, based on the analytical dependence of the measured spectrum on the structural and morphological parameters of the skin, affecting the optical conditions in the medium, and an algorithm for rapid calculation of the bilirubin photoisomerization rate in the skin tissues as a function of the structural and morphological parameters of the skin and the wavelength of the exciting radiation. From the results of a numerical simulation of the process of radiation transport in the skin, we assess the stability of our method to variations in the scattering properties of the skin and the concentrations of its optically active chromophores (melanin, oxyhemoglobin, deoxyhemoglobin). We show that in order to achieve the maximum efficacy of phototherapy, we should use light from the range 484-496 nm. In this case, the intensity of the exciting radiation should be selected individually for each newborn according to the bilirubin photoisomerization rate characteristic for it.

  3. Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats. (United States)

    Hagiwara, Hiroko; Funabashi, Toshiya; Mitsushima, Dai; Kimura, Fukuko


    There are sex differences in nociceptive behavior induced by formalin in rats. To determine whether these sex differences are the result of the sexual differentiation of the brain, that is masculinization and defeminization [A.P. Arnold, R.A. Gorski, Gonadal steroid induction of structural sex differences in the central nervous system, Annu. Rev. Neurosci. 7 (1984) 413-442; M.M. McCarthy, A.T.M. Konkle, When is a sex difference not a sex difference? Front Neuroendocrinol. 26 (2005) 85-102], some female rats were injected with testosterone propionate (TP, 100 microg/25 microl/rat) on the day of birth and on the following day. As controls, other female rats and all male rats were injected with the same volume of sesame oil. They were castrated at the age of 8 weeks, and implanted with a silicon tube containing 20% of 17beta-estradiol or cholesterol. Two weeks after the implantation, rats were injected with 50 microl of 2% formalin in the right hind paw and their behavioral changes were observed for 1h. In cholesterol-implanted rats, all rats exhibited three typical phases of pain response and there were no significant differences in the scores of nociceptive behavior. In 17beta-estradiol implanted rats, female and TP-treated female rats had a significantly higher score of nociceptive behavior than male rats. These results indicate that estrogen produces sex differences in nociceptive behavior induced by formalin, and suggest that these differences are not due to the sexual differentiation of the brain, since the dose and the timing of the TP treatment effectively defeminize and masculinize female rats. Alternatively, sexual differentiation of the brain response to formalin-induced nociceptive behavior may be different from ordinary sexual differentiation.

  4. Fluoxetine impairs GABAergic signaling in hippocampal slices from neonatal rats

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    Enrico eCherubini


    Full Text Available Fluoxetine (Prozac, an antidepressant known to selectively inhibit serotonin reuptake, is widely used to treat mood disorders in women suffering from depression during pregnancy and postpartum period. Several lines of evidence suggest that this drug, which crosses the human placenta and is secreted into milk during lactation, exerts its action not only by interfering with serotoninergic but also with GABAergic transmission. GABA is known to play a crucial role in the construction of neuronal circuits early in postnatal development. The immature hippocampus is characterized by an early type of network activity, the so-called Giant Depolarizing Potentials (GDPs, generated by the synergistic action of glutamate and GABA, both depolarizing and excitatory. Here we tested the hypothesis that fluoxetine may interfere with GABAergic signaling during the first postnatal week, thus producing harmful effects on brain development. At micromolar concentrations fluoxetine severely depressed GDPs frequency (IC50 22 M in a reversible manner and independently of its action on serotonin reuptake. This effect was dependent on a reduced GABAergic (but not glutamatergic drive to principal cells most probably from parvalbumin-positive fast spiking neurons. Cholecystokinin-positive GABAergic interneurons were not involved since the effects of the drug persisted when cannabinoid receptors were occluded with WIN55,212-2, a CB1/CB2 receptor agonist. Fluoxetine effects on GABAergic transmission were associated with a reduced firing rate of both principal cells and interneurons further suggesting that changes in network excitability account for GDPs disruption. This may have critical consequences on the functional organization and stabilization of neuronal circuits early in postnatal development.

  5. Adult Rats Treated with Risperidone during Development Are Hyperactive (United States)

    Bardgett, Mark E.; Franks-Henry, Julie M.; Colemire, Kristin R.; Juneau, Kathleen R.; Stevens, Rachel M.; Marczinski, Cecile A.; Griffith, Molly S.


    Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or one of two doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal days 14 – 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first two experiments, early-life risperidone administration was associated with increased locomotor activity at one week post-administration through approximately nine months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set-points for specific behaviors during adulthood. PMID:23750695

  6. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

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    Liang Shu


    Full Text Available Renshaw recurrent inhibition (RI plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S and medial gastrocnemius (MG motor pools was assessed by conditioning monosynaptic reflexes (MSR elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.

  7. Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea. (United States)

    Trefz, Florian M; Lorch, Annette; Feist, Melanie; Sauter-Louis, Carola; Lorenz, Ingrid


    The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a

  8. Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea (United States)


    Background The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. Results After being lifted, many calves were able to stand despite base excess levels below −20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below −5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. Conclusions Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of

  9. Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea

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    Trefz Florian M


    Full Text Available Abstract Background The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration. Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. Results After being lifted, many calves were able to stand despite base excess levels below −20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below −5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l. However, the clinical status was not affected significantly by the metabolic alkalosis. Conclusions Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed

  10. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses


    Yi, Yong-Hong; Guo, Wen-Chao; Sun, Wei-Wen; Su, Tao; Lin, Han; Chen, Sheng-Qiang; Deng, Wen-Yi; Zhou, Wei; Liao, Wei-Ping


    Lamotrigine (LTG), an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen). LTG was administered intra...

  11. 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


    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.

  12. Neonatal domoic acid increases receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions of adult rats

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Wegener, Gregers

    Background: The presymptomatic events involved in neurological disorders such as epilepsy remain elusive but represent an opportunity to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies using Western blot and immunohistochemistry have...... found increased levels of α2 adrenoceptors in the hippocampal membrane of adult rats treated neonatally with low-dose domoic acid (DOM) along with decreased levels of both isoforms of glutamic acid decarboxylase (GAD), a catalyst of the decarboxylation of glutamate to GABA, indicating a reduction......-14 with saline or low sub-convulsive doses of the glutamate agonist DOM (20µg/kg), weaned on day 22 and left undisturbed except for routine husbandry. At ~120 days of age the rats were euthanized by decapitation. The brains were removed, frozen in isopentane/dry ice and cut into 20 µM thick slices. Receptor...

  13. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

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    Saleh A. Bakheet


    Full Text Available We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients.

  14. 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.


    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:

  15. Effects of cyclosporin A and cyclophosphamide on Peyer's patches in rat, exposed in utero and neonatally or during adult age

    NARCIS (Netherlands)

    Kuper, C.F.; Zijverden, M. van; Klaassen, C.; Tegelenbosch-Schouten, M.; Wolterbeek, A.P.M.


    The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies,

  16. 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

  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. 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


    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 d...

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


    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

  20. Neonatal exposure to 17β-estradiol down-regulates the expression of synaptogenesis related genes in selected brain regions of adult female rats. (United States)

    Radhika, N S; Govindaraj, Vijayakumar; Sarangi, S K; Rao, A J


    Administration of estradiol or compounds with estrogenic activity to newborn female rats results in irreversible masculinization as well as defeminization in the brain and the animals exhibit altered reproductive behavior as adults. The cellular and molecular mechanism involved in inducing the irreversible changes is largely unknown. In the present study, we have monitored the changes in the expression of selected synaptogenesis related genes in the sexually dimorphic brain regions such as POA, hypothalamus and pituitary following 17β-estradiol administration to neonatal female rats. Female Wistar rats which were administered 17β-estradiol on day 2 and 3 after birth were sacrificed 120days later and the expression levels of genes implicated in synaptogenesis were monitored by semi-quantitative reverse transcription PCR. Since estradiol induced up-regulation of COX-2 in POA is a marker for estradiol induced masculinization as well as defeminization, in the present study only animals in which the increase in expression of COX-2 gene was observed in POA were included in the study. Down-regulation of genes such as NMDA-2B, NETRIN-1, BDNF, MT-5 MMP and TNF-α was observed in the pre-optic area of neonatally E2 treated female rat brain but not in hypothalamus and pituitary compared to the vehicle- treated controls as assessed by RT-PCR and Western blot analysis. Our results suggest a possibility that down-regulation of genes associated with synaptogenesis in POA, may be resulting in disruption of the cyclical regulation of hormone secretion by pituitary the consequence of which could be infertility and altered reproductive behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus. (United States)

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


    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

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

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    Mahmoud Hosseini


    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.

  3. Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in neonatal rats. (United States)

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


    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

  4. The Investigation of Garlic (Allium Sativum Extract on Lead Detoxification of Neonatal Rats Kidney

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    Habibollah Johari


    in kidney poisoning treatment induced by lead in neonatal rat.Materials & Methods: Rats were divided into 7 groups of 8. The First group was the control group, which had received no materials. The second group had received 0/1 ml distilled water, the third group had received the lead with a dose of 0/6 gram per liter. The forth group had just received 0/4 g/kg garlic alcoholic – water extract. The fifth, sixth, and seventh group had first received 0/6 g lead perliter and then received doses of 0/1, 0/2, 0/4 g/kg garlic. Then, injections was performed orally in 10 consecutive days. The data were analysed then using T. Results: Based on the obtained results, there is a significant increase in the body weight and the kidney of the third, fifth, sixth and seventh groups compared with the control group. However, the body weight and kidney of rats in the fourth group showed a meaningful decrease comparing with the lead group. Regarding the third group, there was a meaningful increase in Urea, uric acid, creatinine and potassium compared with the control group but a significant decrease in the sodium. Conclusion: Protective effects of garlic on kidney are related to antioxidant properties, since different types of oxidation reactions have negative effects on glomerular filtration rate. Garlic is eliminating the poisoning effect of lead on the kidney because of having properties such as antioxidant and protective effect.

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

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    Maylis Tartas


    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.

  6. Assessment of serum magnesium levels and its outcome in neonates of eclamptic mothers treated with low-dose magnesium sulfate regimen (United States)

    Das, Monalisa; Chaudhuri, Patralekha Ray; Mondal, Badal C.; Mitra, Sukumar; Bandyopadhyay, Debasmita; Pramanik, Sushobhan


    Objectives: Magnesium historically has been used for treatment and/or prevention of eclampsia. Considering the low body mass index of Indian women, a low-dose magnesium sulfate regime has been introduced by some authors. Increased blood levels of magnesium in neonates is associated with increased still birth, early neonatal death, birth asphyxia, bradycardia, hypotonia, gastrointestinal hypomotility. The objective of this study was to assess safety of low-dose magnesium sulfate regimen in neonates of eclamptic mothers treated with this regimen. Materials and Methods: This was a cross-sectional observational study of 100 eclampsia patients and their neonates. Loading dose and maintenance doses of magnesium sulfate were administered to patients by combination of intravenous and intramuscular routes. Maternal serum and cord blood magnesium levels were estimated. Neonatal outcome was assessed. Results: Bradycardia was observed in 18 (19.15%) of the neonates, 16 (17.02%) of the neonates were diagnosed with hypotonia. Pearson Correlation Coefficient showed Apgar scores decreased with increase in cord blood magnesium levels. Unpaired t-test showed lower Apgar scores with increasing dose of magnesium sulfate. The Chi-square/Fisher's exact test showed significant increase in hypotonia, birth asphyxia, intubation in delivery room, Neonatal Intensive Care Unit (NICU) care requirement, with increasing dose of magnesium sulfate. (P ≤ 0.05). Conclusion: Several neonatal complications are significantly related to increasing serum magnesium levels. Overall, the low-dose magnesium sulfate regimen was safe in the management of eclamptic mothers, without toxicity to their neonates. PMID:26600638

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

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    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

  8. Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome (United States)

    Hartley, Stephen W.; Coon, Steven L.; Savastano, Luis E.; Mullikin, James C.; Fu, Cong; Klein, David C.


    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 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 biology. PMID:26367423

  9. Effects of neonatal fluoxetine exposure on behavior across development in rats selectively bred for an infantile affective trait. (United States)

    Zimmerberg, Betty; Germeyan, Sierra C


    Infants born to women with depressive symptoms are at higher risk for insecure attachment and behavioral problems. Thus current medical practice is to continue psychotropic medication of pregnant women with depression despite concerns about its behavioral teratology. There are few animal studies focused on long-term behavioral effects of prenatal antidepressant exposure; in addition, studies have not looked at individual differences in baseline affective state as a source of response variability. In this study, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was administered to male and female rat pups from postnatal days 2-7 to model exposure to antidepressants in the human third trimester. Four behavioral measures were conducted from the neonatal to adult age periods in Low and High lines selectively bred for their rate of ultrasonic vocalizations after brief maternal separation. Neonatal fluoxetine administration decreased distress calls in both lines, but to a greater extent in High line rats than Low line. Neonatal fluoxetine also impaired motor coordination in neonates. Neonatal fluoxetine administration decreased social behavior in both juvenile and adult subjects. Fluoxetine-related reductions in anxiety behavior were not observed at the two older ages. As expected, High line subjects displayed more anxiety behavior than Low line subjects at all three test ages. These results suggest that there are may be significant behavioral consequences of antidepressant use during late pregnancy on offspring maternal attachment and social behavior, with implications for increased risk of autism spectrum disorders. © 2014 Wiley Periodicals, Inc.

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

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    E.E.S. Hermel


    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.

  11. Effects of neonatal decortication on the social play of juvenile rats. (United States)

    Panksepp, J; Normansell, L; Cox, J F; Siviy, S M


    The effects of radical neonatal decortication on the social play of juvenile rats, as well as the effects of neonatal ablation of frontal or parietal cortex, were examined in this series of experiments. When total decorticates were tested in like-lesioned pairs, the frequency of pinning was reduced by about 50% and their average pin durations were shorter. Nevertheless, the play of decorticates appeared essentially normal in general appearance, and did not differ from controls in a measure of overall play vigor using an electronic activity platform. Further, there were no differences in pin frequencies when controls and decorticates were paired together in cross-lesion testing. Separate tests of play solicitation behaviors did not detect any differences between controls and decorticates suggesting that play motivation was essentially intact after decortication. No deficits in pinning resulted from frontal ablations; however, pin durations were shorter in like-lesion testing. In cross-lesion testing, there was an increase in dorsal contacts and a trend toward shortening of pin durations. Parietal aspirations resulted in a 65% reduction in pin frequency, without substantially altering dorsal contacts. Anesthetization of the anterior surface of the animal's back with xylocaine reduced pinning in controls but eliminated pinning in parietals. Although the results generally indicate little participation of the neocortex in the instigation of rough-and-tumble play, the reliable numerical changes that were observed may be explained by apparent motor changes as well as reduced somatosensory sensitivity.

  12. Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia. (United States)

    Lee, Ben H; Wen, Tong-Chun; Rogido, Marta; Sola, Augusto


    Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI). GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group. Nissl staining was performed on FCI or S-O P7 cortical samples. Cortical GR expression was increased by 65.2% at P7, 110.1% at P15, and 87.0% at P30, compared to P1. On P7, GR expression decreased in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI (p cortex after 6 h and in the non-ischemic cortex after 24 h of FCI. Thus, cortical GR may play important roles in normal brain development and neonatal brain injury responses.

  13. Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats. (United States)

    Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc


    Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Role of gravity in the development of posture and locomotion in the neonatal rat. (United States)

    Clarac, F; Vinay, L; Cazalets, J R; Fady, J C; Jamon, M


    This report describes the early motor behaviour in the neonatal rat in relation with the maturation of sensory and motor elements of the central nervous system (CNS). The role of vestibular information during the week before (E14-21) and the 2 weeks after (P0-15) birth will be considered. There is a rostro-caudal gradient in the maturation of posture and locomotion with a control of the head and forelimbs during the first postnatal week and then a sudden acceleration in the functional maturation of the hindlimb. At birth, the neonatal rat is blinded and deaf; despite the immaturity of the other sensory systems, the animal uses its olfactory system to find the mother nipple. Vestibular development takes place between E8 and P15. Most descending pathways from the brainstem start to reach the lumbar enlargement of the spinal cord a few days before birth (reticulo-, vestibulospinal pathways as well as the serotonergic and noradrenergic projections); their development is not completed until the end of the second postnatal week. At birth, in an in vitro preparation, a locomotor activity can be evoked by perfusing excitatory amino acids and serotonin over the lumbar region. The descending pathways which trigger the activity of the CPG are also partly functional. At the same age both air stepping and swimming can be induced. Complex locomotion such as walking, trotting and galloping start later because it requires the maturation of the vestibular system, descending pathways and postural reflex regulation. The period around birth is critical to properly define how the vestibular information is essential for the structuring of the motor behaviour. Different types of experiments (hypergravity, microgravity) are planned to test this hypothesis. Copyright 1998 Elsevier Science B.V.

  15. Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia. (United States)

    Marcelino, Thiago Beltram; de Lemos Rodrigues, Patrícia Idalina; Miguel, Patrícia Maidana; Netto, Carlos Alexandre; Pereira Silva, Lenir Orlandi; Matté, Cristiane


    Pregnancy is a critical period for brain metabolic programming, being affected by individual environment, such as nutrition, stress, and physical exercise. In this context, we previously reported a cerebral antioxidant upregulation and mitochondrial biogenesis in the offspring delivered from exercised mothers, which could provide neuroprotection against neonatal insults. Hypoxia-ischemia (HI) encephalopathy is one of the most studied models of neonatal brain injury; disrupting motor, cognitive, and learning abilities. Physiopathology includes oxidative stress, allied to mitochondria energy production failure, glutamatergic excitotoxicity, and cell death. In this study we evaluated the effect of maternal swimming during pregnancy on offspring׳s brain oxidative status evaluated fourteen days after HI stablishment. Swimming exercise was performed by female adult rats one week before and during pregnancy, in controlled environment. Their offspring was submitted to HI on postnatal day 7, and the brain samples for biochemical assays were obtained in the weaning. Contrary to our expectations, maternal exercise did not prevent the oxidative alterations observed in brain from HI-rats. In a general way, we found a positive modulation in the activities of antioxidant enzymes, measured two weeks after HI, in hippocampus, striatum, and cerebellum of pups delivered from exercised mothers. Reactive species levels were modulated differently in each structure evaluated. Considering the scenery presented, we concluded that HI elicited a neurometabolic adaptation in both brain hemispheres, particularly in hippocampus, parietal cortex, and cerebellum; while striatum appears to be most damaged. The protocol of aerobic maternal exercise was not enough to fully prevent HI-induced brain damages. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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    Farimah Beheshti


    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

  17. Targeted intracellular catalase delivery protects neonatal rat myocytes from hypoxia-reoxygenation and ischemia-reperfusion injury (United States)

    Undyala, Vishnu; Terlecky, Stanley R.; Vander Heide, Richard S.


    Hypoxia followed by reoxygenation (HR) and ischemia-reperfusion (IR) cause cell death in neonatal rat ventricular myocytes (NRVM) primarily through the generation of oxidative stress. Extracellular catalase (CAT) has not been effective in reducing or eliminating IR or HR-induced cell death due both to extracellular degradation and poor cellular uptake. Aims 1) to determine if a cell penetrating catalase derivative with enhanced peroxisome targeting efficiency (catalase-SKL) increases intracellular levels of the antioxidant enzyme in NVRM; and 2) to determine if catalase-SKL protects against both HR and IR injury. Methods NRVM were subjected to 3 or 6 hr of HR or 1 hr of IR. CAT concentration, activity, and subcellular distribution were determined using standard techniques. Reactive oxygen species (ROS) and related oxidative stress were visualized using 2’,7’-dichlorofluorescin diacetate. Cell death was measured using trypan blue exclusion or lactate dehydrogenase (LDH) release assays. Results CAT activity was higher in (catalase-SKL) transduced myocytes, was concentrated in a membranous cellular fraction, and potently inhibited oxidative stress. In contrast to non-transducible (unmodified) CAT, catalase-SKL-treated myocytes were protected against both HR and IR. Conclusions 1) catalase-SKL increased myocyte CAT content and activity and dramatically increased resistance to hydrogen peroxide-induced oxidation; 2) catalase-SKL protects against both HR and IR; 3) catalase-SKL may represent a new therapeutic approach to protect hearts against myocardial HR or IR. PMID:20708413

  18. Ghrelin protected neonatal rat cardiomyocyte against hypoxia/reoxygenation injury by inhibiting apoptosis through Akt-mTOR signal. (United States)

    Wang, Lifeng; Lu, Yingjie; Liu, Xian; Wang, Xiaoyun


    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.

  19. Neonatal handling reduces angiotensin II receptor density in the medial preoptic area and paraventricular nucleus but not in arcuate nucleus and locus coeruleus of female rats. (United States)

    Gomes, Cármen Marilei; Donadio, Márcio Vinícius Fagundes; Franskoviaki, Inélia; Anselmo-Franci, Janete A; Franci, Celso Rodrigues; Lucion, Aldo Bolten; Sanvitto, Gilberto Luiz


    Neonatal handling alters the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonads axis (HPG) in adult animals, and angiotensin II (Ang II) modulates the functions in these axes. We tested whether neonatal handling could change the density of Ang II receptors in some central areas in female rats. Results showed decreased density of the Ang II receptors in the medial preoptic area (MPOA) and hypothalamic paraventricular nucleus (PVN) of the neonatal handled group.

  20. Insulin Sensitivity, Leptin, Adiponectin, Resistin, and Testosterone in Adult Male and Female Rats After Maternal-Neonatal Separation and Environmental Stress. (United States)

    Raff, Hershel; Hoeynck, Brian; Jablonski, Mack; Leonovicz, Cole; Phillips, Jonathan M; Gehrand, Ashley L


    Care of premature infants often requires parental and caregiver separation particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented with external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]), plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults with prior neonatal hypoxia allowing spontaneous hypothermia Exposure of neonates to daily hypoxia while preventing spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines, and that our rat model of prematurity with hypoxia with the prevention of hypothermia alters adult testosterone dynamics. Copyright © 2017, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

  1. Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats. (United States)

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


    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.

  2. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence. (United States)

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


    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

  3. 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.


    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.

  4. [Irradiation of 235 uranium on the growth, behavior and some biochemical changes of brain in neonatal rats]. (United States)

    Gu, G; Zhu, S; Wang, L; Yang, S


    The effects of enriched uranium on growth, behavior and biochemical changes of brain in neonatal Wistar rats was studied. Neonatal rats were irradiated with a single injection of 2 microliters enriched uranium (containing 0, 1, 5 and 10 micrograms of 235U) into left lateral ventricle of brain at the first day (< 24 h) after birth. The growth and neurobehavior development of the rats was delay and abnormal. The microautoradiographic tracing technique showed that the radionuclide was mainly accumulated in the nucleus, also appeared in the cytoplasm of cells and between cells. The activity of superoxide dismutase (SOD) and the level of endothelin (ET) of cerebellum, cerebral cortex, hippocampus and diencephalons of brain after exposure to alpha irradiation were examined with radioimmunoassay. The data indicated that SOD and ET was elevated by low dose irradiation and distinctly inhibited by high dose irradiation. It was concluded that alpha irradiation could have damages on the developing brain of neonatal rats characterized by changing the sensibility, fragility and compensation of nerve cells.

  5. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats. (United States)

    Ren, Xiaoyan; Ma, Hong; Zuo, Zhiyi


    Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues.

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

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    Amanda L. Smith


    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.

  7. Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates.

    NARCIS (Netherlands)

    Claahsen-van der Grinten, H.L.; Verbruggen, I.; Berg, P.P. van den; Sporken, J.M.J.; Kollee, L.A.A.


    OBJECTIVE: The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain.METHODS: Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving

  8. Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats. (United States)

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


    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

  9. Maternal and Neonatal Effects of Vasopressors Used for Treating Hypotension after Spinal Anesthesia for Caesarean Section: A Randomized Controlled Study. (United States)

    Soxhuku-Isufi, Alma; Shpata, Vjollca; Sula, Hektor


    The aim of the study was to examine whether ephedrine and phenylephrine were different in their efficacy for managing maternal hypotension and their effect of adverse maternal and neonatal outcome. A double-blind randomized controlled study in healthy pregnant women ASA physical status 2, which underwent elective caesarian delivery under spinal anesthesia. Patients were randomized to receive an intravenous bolus of either phenylephrine (Ph group) or ephedrine (E group) immediately after the episode of hypotension after spinal anesthesia. Maternal and neonatal outcomes were recorded. Two hundred and two (202) pregnant women at term were entered in this study. There were no differences between group E and group Ph regarding the incidence of hypotension after vasopressor therapy, and the incidence of nausea and vomiting. There was no significant difference between groups in the first-minute and the 5th minute Apgar score, none of the neonates had the true fetal acidosis. Ephedrine and phenylephrine have the same efficacy in treating hypotension after spinal anesthesia for caesarean section. The use of Phenylephrine was associated with better fetal acid-base status, and there were no differences on Apgar score values and on the incidence of maternal bradycardia and hypotension.

  10. Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. (United States)

    Granata, Riccarda; Volante, Marco; Settanni, Fabio; Gauna, Carlotta; Ghé, Corrado; Annunziata, Marta; Deidda, Barbara; Gesmundo, Iacopo; Abribat, Thierry; van der Lely, Aart-Jan; Muccioli, Giampiero; Ghigo, Ezio; Papotti, Mauro


    The ghrelin gene products, namely acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob), were shown to prevent pancreatic beta-cell death and to improve beta-cell function under treatment with cytokines, which are major cause of beta-cell destruction in diabetes. Moreover, AG had been described previously to prevent streptozotocin (STZ)-induced diabetes in rats; however, the effect of either UAG or Ob has never been examined in this context. In the present study, we investigated the potential of UAG and Ob to increase islet beta-cell mass and to reduce diabetes at adult age in STZ-treated neonatal rats. One-day-old rats were injected with STZ and subsequently administered with either AG, UAG or Ob for 7 days. On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. Similarly to AG, both UAG and Ob counteracted STZ-induced high glucose levels and improved plasma and pancreatic insulin levels, which were reduced by the diabetogenic compound. UAG and Ob increased islet area, islet number, and beta-cell mass with respect to STZ treatment alone. Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. Taken together, our results suggest that in STZ-treated newborn rats, UAG and Ob improve glucose metabolism and preserve islet cell mass, granting a therapeutic potential in medical conditions associated with impaired beta-cell function.

  11. Inhibition of miRNA-210 reverses nicotine-induced brain hypoxic-ischemic injury in neonatal rats. (United States)

    Wang, Lei; Ke, Jun; Li, Yong; Ma, Qinyi; Dasgupta, Chiranjib; Huang, Xiaohui; Zhang, Lubo; Xiao, DaLiao


    Maternal tobacco use in pregnancy increases the risk of neurodevelopmental disorders and neurobehavioral deficits in postnatal life. The present study tested the hypothesis that perinatal nicotine exposure exacerbated brain vulnerability to hypoxic-ischemic (HI) injury in neonatal rats through up-regulation of miR-210 expression in the developing brain. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. Experiments of HI brain injury were performed in 10-day-old pups. Perinatal nicotine treatment significantly decreased neonatal body and brain weights, but increased the brain to body weight ratio. Perinatal nicotine exposure caused a significant increase in HI brain infarct size in the neonates. In addition, nicotine enhanced miR-210 expression and significantly attenuated brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase isoform B (TrkB) protein abundance in the brain. Of importance, intracerebroventricular administration of a miR-210 inhibitor (miR-210-LNA) significantly decreased HI-induced brain infarct size and reversed the nicotine-increased vulnerability to brain HI injury in the neonate. Furthermore, miR-210-LNA treatment also reversed nicotine-mediated down-regulation of BDNF and TrkB protein expression in the neonatal brains. These findings provide novel evidence that the increased miR-210 plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the brain. It represents a potential novel therapeutic approach for treatment of brain hypoxic-ischemic encephalopathy in the neonate-induced by fetal stress.

  12. Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat. (United States)

    Hanlon, L A; Raghupathi, R; Huh, J W


    The role of microglia in the pathophysiology of injury to the developing brain has been extensively studied. In children under the age of 4 who have sustained a traumatic brain injury (TBI), markers of microglial/macrophage activation were increased in the cerebrospinal fluid and were associated with worse neurologic outcome. Minocycline is an antibiotic that decreases microglial/macrophage activation following hypoxic-ischemia in neonatal rodents and TBI in adult rodents thereby reducing neurodegeneration and behavioral deficits. In study 1, 11-day-old rats received an impact to the intact skull and were treated for 3days with minocycline. Immediately following termination of minocycline administration, microglial reactivity was reduced in the cortex and hippocampus (pminocycline treatment did not reduce axonal injury or degeneration. In the thalamus, minocycline treatment did not affect microglial reactivity, axonal injury and degeneration, and neurodegeneration. Injury-induced spatial learning and memory deficits were also not affected by minocycline. In study 2, to test whether extended dosing of minocycline may be necessary to reduce the ongoing pathologic alterations, a separate group of animals received minocycline for 9days. Immediately following termination of treatment, microglial reactivity and neurodegeneration in all regions examined were exacerbated in minocycline-treated brain-injured animals compared to brain-injured animals that received vehicle (pminocycline treatment, memory deficits appeared to be significantly worse (pminocycline treatment. Collectively, these data demonstrate the differential effects of minocycline in the immature brain following impact trauma and suggest that minocycline may not be an effective therapeutic strategy for TBI in the immature brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training. (United States)

    Ribeiro, Carla; Cambri, Lucieli T; Dalia, Rodrigo A; Araújo, Michel B; Ghezzi, Ana C; Moura, Leandro P; Araújo, Gustavo G; Botezelli, Jose D; Mello, Maria Ar


    This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. 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. 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. It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.

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

    Directory of Open Access Journals (Sweden)

    Ribeiro Carla


    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.

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

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    Mariangela Serra


    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

  16. Feasibility and efficacy of gentamicin for treating neonatal sepsis in community-based settings: a systematic review. (United States)

    Jaiswal, Nishant; Singh, Meenu; Kondel, Ritika; Kaur, Navjot; Thumburu, Kiran K; Kumar, Ajay; Kaur, Harpreet; Chadha, Neelima; Gupta, Neeraj; Agarwal, Amit; Malhotra, Samir; Shafiq, Nusrat


    Neonatal sepsis is a leading cause of neonatal deaths in developing countries. The current recommended in-hospital treatment is parenteral ampicillin (or penicillin) and gentamicin in young infants for 10- 14 days; however, very few could access and afford. The current review is to evaluate the feasibility of gentamicin in community based settings. Both observational and randomized controlled trials were included. Medline, Embase, Cochrane Central Register of Controlled Trials and Central Trial Register of India were searched until September 2013. We assessed the risk of bias by Cochrane Collaboration's "risk of bias" tool. Two observational studies indicated feasibility ensuring coverage of population, decrease in case fatality rate in the group treated by community health workers. In an RCT, no significant difference was observed in the treatment failure rates [odds ratio (OR)=0.88], and the mortality in the first and second week (OR=1.53; OR=2.24) between gentamicin and ceftriaxone groups. Within the gentamicin group, the combination of penicillin and gentamicin showed a lower rate of treatment failure (OR=0.44) and mortality at second week of life (OR=0.17) as compared to the combination of gentamicin and oral cotrimoxazole. Gentamicin for the treatment of neonatal sepsis is both feasible and effective in community-based settings and can be used as an alternative to the hospitalbased care in resource compromised settings. But there was less evidence in the management of neonatal sepsis in hospitals as was seen in this review in which we included only one RCT and three observational studies.

  17. Spatiotemporal characteristics of 5-HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat

    DEFF Research Database (Denmark)

    Kiehn, O; Kjaerulff, O


    1. Rhythmic activity was induced with either serotonin (5-HT; 10-100 microM) or dopamine (0.1-1.0 mM), in the in vitro spinal cord preparation of neonatal rats, with one intact hindlimb attached. Patterns of activity were investigated with multiple EMG recordings and the spatiotemporal characteri......1. Rhythmic activity was induced with either serotonin (5-HT; 10-100 microM) or dopamine (0.1-1.0 mM), in the in vitro spinal cord preparation of neonatal rats, with one intact hindlimb attached. Patterns of activity were investigated with multiple EMG recordings and the spatiotemporal...... flexor-extensor transition in older animals. 7. The complex timing of hindlimb muscle activity was relatively unchanged after transecting all dorsal roots. 8. Finally, the relationship between flexor and extensor activity and ventral root discharges was determined. It was found that the L2 ventral root...

  18. Neonatal ethanol produces cerebellar deep nuclear cell loss and correlated disruption of eyeblink conditioning in adult rats. (United States)

    Green, John T; Tran, Tuan; Steinmetz, Joseph E; Goodlett, Charles R


    Binge-like neonatal exposure to ethanol (EtOH) in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent Purkinje cell loss in the cerebellum and deficits in eyeblink classical conditioning. There are currently no published reports of whether neuronal loss in the cerebellar deep nuclei also results from binge-like neonatal exposure to EtOH and what the functional consequences of any cell loss might be. Since eyeblink conditioning requires cerebellar deep nuclear cells for normal learning to occur, we examined the effects of binge-like neonatal EtOH exposure on the total number of deep nuclear cells and eyeblink conditioning in adult rats. Group Ethanol (n=11) received EtOH doses of 5.25 g/kg/day on postnatal days 4-9, producing average peak blood alcohol concentrations of 363 mg/dl. Group Sham Intubated (n=11) underwent acute intragastric intubation on postnatal days 4-9 but did not receive any EtOH infusions. Group Unintubated Control (n=10) did not receive any intubations. When rats were at least 3 months old, they received either paired eyeblink conditioning or unpaired training. Following training, estimates of the total number of cerebellar deep nuclear cells were obtained using the optical fractionator, an unbiased stereological counting procedure. Rats in Group Ethanol had approximately 50% fewer deep nuclear cells compared to rats in Groups Sham Intubated and Unintubated Control, which did not differ. For 21 rats that received paired eyeblink conditioning, a highly significant correlation (+0.80) was found between the number of deep nuclear cells and learning rate in eyeblink conditioning. Copyright 2002 Elsevier Science B.V.

  19. Haematological and Serum Biochemical Variables in rats Treated ...

    African Journals Online (AJOL)

    The haematology and serum biochemical effects of oral administration of the ethanolic extract of the root of Moringa oleifera at 50, 100 and 150 mg/kg were investigated in 30 mated female Wistar rats. The rats were assigned into five groups of six rats each. Group A was given 50mg/kg of the extract; group B, 100mg/kg; ...

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


    Ortiz-Butron, Rocio


    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...

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


    Schwarz, Jaclyn M.; McCarthy, Margaret M.


    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 mech...

  2. A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats


    McClelland, David; Evans, Rhian M; Barkworth, Louise; Martin, Duncan J; Scott, Roderick H


    Background Gabapentin and pregabalin have wide-ranging therapeutic actions, and are structurally related to the inhibitory neurotransmitter GABA. Gabapentin, pregablin and GABA can all modulate voltage-activated Ca2+ channels. In this study we have used whole cell patch clamp recording and fura-2 Ca2+ imaging to characterise the actions of pregabalin on the electrophysiological properties of cultured dorsal root ganglion (DRG) neurones from neonatal rats. The aims of this study were to determ...

  3. Effects of neonatal and adolescent neuroactive steroid manipulation on locomotor activity induced by ethanol in male wistar rats. (United States)

    Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc


    Neonatal neuroactive steroids levels are crucial for brain development. Alterations of neonatal neuroactive steroids levels induce anxiolytic-like effects and improve exploration in novel environments in adulthood. These behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are associated with vulnerability to drug use and abuse. Adolescence is also recognized as a particularly critical developmental phase to contribute to vulnerable phenotype. However, the influence of neuroactive steroids during development in the vulnerability to drug addiction has been poorly studied. The aim of the present experiment is to study the effect of early neonatal and adolescent manipulations of neuroactive steroids on the sensitivity to the stimulant effects of ethanol in adult male rats. Therefore, allopregnanolone or finasteride, an allopregnanolone synthesis inhibitor, were injected from postnatal day 5-9. In early adolescence, half of the subjects were injected with progesterone, the main allopregnanolone precursor, and the elevated plus-maze anxiety test was performed. Results indicated that early adolescent progesterone induced anxiolytic-like effects (increase in the percentage of entries and time in open arms). Neonatal finasteride administration decreased locomotor activity induced by ethanol in adolescent vehicle subjects. Interestingly, differences induced by neonatal treatments were not present in the animals that received progesterone in the early adolescence. In conclusion, neuroactive steroid manipulations in crucial stages of development could be playing an important role in behavioural effects of alcohol such as the sensitivity to locomotor stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Neonatal injury rapidly alters markers of pain and stress in rat pups. (United States)

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


    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.

  5. Gastroesophageal reflux disease in neonates and infants : when and how to treat. (United States)

    Czinn, Steven J; Blanchard, Samra


    infants. In these infants, symptoms decrease significantly within 2-4 weeks after elimination of cow's milk protein from the diet. For non-complicated reflux, no intervention is required for most infants. Effective parental reassurance and education regarding regurgitation and lifestyle changes are usually sufficient to manage infant reflux. Sandifer syndrome, apnea and apparent life-threatening events are the extraesophageal manifestations of GERD in infants. Pharmacotherapeutic agents used to treat GERD encompass antisecretory agents, antacids, surface barrier agents and prokinetics. Currently, North American Society for Pediatric Gasroenterology, Hepatology and Nutrition (NASPGHAN) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) practice guidelines concluded that there is insufficient evidence to justify the routine use of prokinetic agents. Esomeprazole (Nexium) is now approved in the US for short-term treatment of GERD with erosive esophagitis in infants aged from 1 to 12 months. Although Nissen fundoplication is now well established as a treatment option in selected cases of GERD in children, its role in neonates and young infants is unclear and is only reserved for selective infants who did not respond to medical therapy and have life-threatening complications of GERD.

  6. Effects of sevoflurane on learning, memory, and expression of pERK1/2 in hippocampus in neonatal rats. (United States)

    Yu, X; Liu, Y; Bo, S; Qinghua, L


    Sevoflurane may be associated with neural toxicity in the developing brain, but the mechanism is still unclear. Phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) are important for developing neurons. The aim of our study was to investigate the effects of sevoflurane on spatial learning and memory and on expression of pERK1/2 in hippocampus of neonatal rats. Sixty-three neonatal rats were randomly divided into three groups: control group, sevoflurane (sevo) group, and sham group. Rats in the control group were placed in a plastic chamber flushed continuously for 4 h with air alone, rats in the sevo group were exposed in 5% sevoflurane and air for 4 h, and rats in the sham group were exposed in 5% carbon dioxide and air for 4 h, with identical flow rates for all groups. All three groups were subjected to Morris water maze test 1 day after sevoflurane exposure. Moreover, expression of pERK1/2 was determined by immunochemistry and Western blot at 1, 3, and 6 weeks after exposure. Compared with the control group, the escape latency was longer in sevo group and the expression of pERK1/2 was significantly inhibited in the sevo group (P learning and memory, and this may be attributed to decreased pERK1/2 in the hippocampus. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

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    Wadah Khriesat


    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  8. Severe neonatal CMV infection complicated with thrombotic microangiopathy successfully treated with ganciclovir. (United States)

    Mitsuiki, Noriko; Tamanuki, Keita; Sei, Kenshi; Ito, Jun; Kishi, Aiko; Kobayashi, Kenji; Hatai, Yoshiho; Nagasawa, Masayuki


    We report a neonate of severe cytomegalovirus (CMV) infection who presented vomiting, severe thrombocytopenia and thrombotic microangiopathy (TMA). He showed occasional vomiting at 3 weeks of age and visited us with systemic petechiae at 29 days old. Platelet was markedly decreased to 18,000/μL and fragmented red blood cells were increased in the peripheral blood. Intravenous ganciclovir (GCV) administration was started at 35 days old after detection of CMV in the peripheral blood. His normal values of T-cell receptor excision circles (TREC) and signal joint kappa-deleting recombination excision circles (sjKREC) excluded the possibility of severe immunodeficiency. Congenital CMV infection was denied later, when CMV of the dried blood spot obtained for neonatal mass-screening at 4 days old was proved negative. We provided 6-week treatment with no side effect such as myelosuppression. The left hearing abnormality found at first was improved along with other symptoms. GCV seems to be effective and safe for severe neonatal CMV infection. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Orosensory deprivation alters taste-elicited c-Fos expression in the parabrachial nucleus of neonatal rats (United States)

    Haino, Toshiyuki; Hironaka, Shouji; Ooka, Takafumi; Tokita, Kenichi; Kubota, Yu; Boughter, John D.; Inoue, Tomio; Mukai, Yoshiharu


    In the present study we examined the effects of neonatal orosensory deprivation on taste-elicited gustatory activity in the rat parabrachial nucleus (PBN) using the functional anatomical marker c-Fos. Animals in three groups (GG, GO and GM) received gastric cannula implantation surgery on postnatal day 9 (P9). Animals in the fourth group (MR) did not receive any surgery. GG rats were fed by infusion of artificial milk directly into the stomach. GO rats were fed by intraoral infusion of artificial milk. GM and MR rats were reared by their mother with free access to mother’s milk, water and rat chow. Rats from all groups were similar in body weight and length by P21. On P21 rats in all groups were intraorally presented with 0.5 M sucrose solution and the brains were extracted and processed for c-Fos immunohistchemistry. Taste-elicited c-Fos expression in both the gustatory waist area, and the external lateral subnucleus of the PBN in rats in the GG group was significantly more robust than in the other three groups. These findings suggest a substantial alteration in orosensory-evoked neuronal response in this nucleus, due to sensory or motor deprivation during a critical developmental stage. PMID:20302893

  10. Retrospective Cohort Study Comparing Neonatal Outcomes of Women Treated with Glyburide or Insulin in Gestational Diabetes: A 5-Year Experience in a South Indian Teaching Hospital


    Jiji Elizabeth Mathews; Biwas Biswas; Prasanna Samuel; Atanu Kumar Jana; Jaya Prakash Muliyil; Matthews Mathai


    Objective: To assess the effectiveness of glyburide in preventing complications of gestational diabetes in neonates as compared to insulin. Materials and Methods: Information from birth register, maternal and neonatal records were obtained. Five hundred and seventy-seven gestational diabetics with moderate hyperglycemia i.e., with highest fasting plasma glucose value of ≤130 mg/dl and/or highest post-prandial value of ≤250 mg/dl treated with insulin or glyburide were included from a cohort of...

  11. Extracellular receptor kinase and cAMP response element binding protein activation in the neonatal rat heart after perinatal cocaine exposure. (United States)

    Sun, Lena S; Quamina, Aaron


    Prenatal exposure to cocaine has been shown to induce an increase in the myocardial expression and activation of the cAMP response binding protein (CREB), a transcriptional factor that has been shown to regulate gene expression. Several different kinases, including protein kinase A, calcium calmodulin kinase II, and mitogen-activated protein kinase can induce phosphorylation of CREB at serine 133, a necessary step for CREB activation. We examined whether the mitogen-activated protein kinase-extracellular receptor kinase (ERK) pathway may be involved in mediating the serine 133 CREB phosphorylation in cardiac nuclei after perinatal cocaine exposure. Pregnant rats were treated daily with saline or cocaine at 60 mg/kg (C60) by intragastric administration during the entire gestational period, and treatment was continued in the nursing dams after delivery until the time of the study. Nuclear extracts were isolated from hearts of 1-d- and 7-d-old neonatal rats. We performed immunoblotting experiments using an antibody that recognized CREB with phosphorylation specifically at the serine 133 site and an antibody that recognized both the phosphorylated and the unphosphorylated forms of CREB, as well as antibodies for total ERK, phospho-ERK, total ribosomal S6 kinase 1 (RSK1), RSK2, and phospho-RSK. We assessed the interaction of RSK with CREB or CREB-binding protein by performing co-immunoprecipitation experiments. We found that perinatal cocaine exposure increased both phospho-ERK and phospho-RSK expression, indicative of an increased activity of these two enzymes. Furthermore, we demonstrated that phospho-RSK was immunoprecipitated with CREB in all neonatal cardiac nuclei and that the greatest interaction was found in day 7 hearts after perinatal cocaine exposure. Our results thus illustrate that the ERK-RSK pathway was active in the postnatal rat heart at 1 and 7 d of age and that this pathway may mediate the increase in myocardial CREB activation after perinatal cocaine

  12. Ontogeny of open field activity in rats after neonatal lesioning of the mesocortical dopaminergic projection

    NARCIS (Netherlands)

    Kalsbeek, A.; de Bruin, J. P.; Matthijssen, M. A.; Uylings, H. B.


    In order to examine the effect of neonatal depletion of the dopaminergic mesocortical projection on the development of a prefrontal cortex-mediated behaviour the ontogeny of open field behaviour was studied after neonatal depletion of cortical dopamine. Cortical dopamine was depleted by neonatal

  13. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals. (United States)

    Tian, Tian; Ni, Hong; Sun, Bao-liang


    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.

  14. Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats. (United States)

    Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi


    Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

  15. Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

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    Manhães de Castro R.


    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.

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


    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.

  17. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

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    Shin Minkyu


    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

  18. Differential maturation of motoneurons innervating ankle flexor and extensor muscles in the neonatal rat. (United States)

    Vinay, L; Brocard, F; Clarac, F


    The first postnatal week is a critical period for the development of posture in the rat. The use of ankle extensor muscles in postural reactions increases during this period. Changes in excitability of motoneurons are probably an important factor underlying this maturation. The aim of this study was to identify whether variations in the maturation exist between motor pools innervating antagonistic muscles. Intracellular recordings in the in vitro brain stem-spinal cord preparation of neonatal rats (from postnatal day 0-5) were used to examine the developmental changes in excitability of motoneurons innervating the ankle flexors (F-MNs) and the antigravity ankle extensors (E-MNs). No significant difference in resting potential, action potential threshold, input resistance or rheobase was observed at birth. The age-related increase in rheobase was more pronounced for F-MNs than for E-MNs. The development of discharge properties of E-MNs lagged behind that of F-MNs. More F-MNs than E-MNs were able to fire repetitively in response to current injection at birth. F-MNs discharged at a higher frequency than E-MNs at all ages. Differences in the duration of action potential afterhyperpolarization accounted, at least partly, for the differences in discharge frequency between E-MNs and F-MNs at birth, and for the age-related increase in firing rate. These results suggest that E-MNs are more immature at birth than F-MNs and that there is a differential development of motoneurons innervating antagonistic muscles. This may be a critical factor in the development of posture and locomotion.

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

    Schellong, Karen; Neumann, Uta; Rancourt, Rebecca C; Plagemann, Andreas


    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. 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 pSGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (pSGA-in-SL rats (pSGA-in-SL regarding Npy/Pomc expression (pSGA 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 appears to be a critical long-term risk factor in 'small-for-gestational-age babies'.

  20. Increase of Long-Term ‘Diabesity’ Risk, Hyperphagia, and Altered Hypothalamic Neuropeptide Expression in Neonatally Overnourished ‘Small-For-Gestational-Age’ (SGA) Rats (United States)

    Schellong, Karen; Neumann, Uta; Rancourt, Rebecca C.; Plagemann, Andreas


    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 pSGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (pSGA-in-SL rats (pSGA-in-SL regarding Npy/Pomc expression (pSGA 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 appears to be a critical long-term risk factor in ‘small-for-gestational-age babies’. PMID:24265718

  1. Testis evaluation of adult Wistar rats after neonatal treatment with fluoxetine - doi: 10.4025/actascibiolsci.v35i1.10946

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    Bruno Mendes Tenorio


    Full Text Available In current assay the serotoninergic system in newly-born Wistar rats underwent pharmacological modification by fluoxetine, a selective serotonin reuptake inhibitor (SSRI, to investigate its repercussion on testicular parameters in adult animals. Thirty animals were distributed according to treatment: control animals (n = 6, animals treated with 1 mg kg-1 (n = 6, 5 mg kg-1 (n = 6, 10 mg kg-1 (n = 6 and 20 mg kg-1 (n = 6 of fluoxetine (IP. When 150 days old, the animals were anesthetized and perfused intra-cardiacally with fixative solution. Testes were routinely processed for inclusion in plastic resin (methacrylate glycol. Further, 4 µm-thick histological sections were stained with toluidine blue/sodium borate 1% and analyzed histometrically. Pharmacological intervention on the serotoninergic system during the postnatal period of the testes development in Wistar rats with fluoxetine chlorohydrate reduced parameters, such as testicular weight, testis liquid weight and seminiferous tubules diameter. However, testicular parameters, such as daily sperm production (DSP, spermatogenesis efficiency (DSP/g/testis and cell population in stage VII of adult animals, were not influenced by fluoxetine chlorohydrate usage during neonatal period. Results show that administration of fluoxetine during 21 days after birth may induce adverse changes in the spermatogenesis of adult rats.  

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

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    Marisol Pineda-Reynoso


    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

  3. Epigenetic Manipulation of Brain-derived Neurotrophic Factor Improves Memory Deficiency Induced by Neonatal Anesthesia in Rats. (United States)

    Wu, Jiang; Bie, Bihua; Naguib, Mohamed


    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.

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


    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.

  5. Use of glucagon to treat neonatal low-output congestive heart failure after maternal labetalol therapy. (United States)

    Stevens, T P; Guillet, R


    Labetalol is used to treat hypertensive crisis in women with preeclampsia. Glucagon was used as a nonselective beta-adrenergic agonist to treat a preterm infant with symptomatic beta-blockade caused by maternal labetalol therapy.

  6. Compare severity of bronchopulmonary dysplasia in neonates with respiratory distress syndrome treated with surfactant to without surfactant. (United States)

    Chotigeat, Uraiwan; Ratchatanorravut, Sombat; Kanjanapattanakul, Wiboon


    The utilization of surfactant replacement therapy had been limited in treatment of respiratory distress syndrome (RDS) due to the high cost especially in developing countries. Nowadays, the National Health Insurance Policy has covered the cost of surfactant for the patients. Therefore, bronchopulmonary dysplasia (BPD) may be found increasing due to increased survival in patients with severe RDS. To compare immediate treatment outcome of severity of BPD and outcome after hospital discharge in neonates with RDS who were treated with or without surfactant. Retrospective cohort study. The data of 54 infants who developed BPD after RDS at Queen Sirikit National Institute of Child Health between January 1st, 2003 and December 31th, 2005 were kept in database format. The database was analyzed for difference between groups and the outcome of immediate treatment, severity of BPD and outcome after hospital discharge were compared. The study group was BPD cases from RDS treated with surfactant compared to control (BPD cases from RDS treated without surfactant) groups. Forty-three (80%) from fifty-four cases had completed data and were included into the present study. There was no statistically significant difference in maternal conditions and neonatal conditions between groups. Antenatal steroid was prescribed more often in RDS without surfactant group than surfactant group. The mean birth weight and gestational age in surfactant and without surfactant groups were 1,179.1 +/- 274.3 gm vs. 1,114.4 +/- 338.3 gm and 29 +/- 1.6 weeks vs. 29.2 +/- 2.7 weeks respectively, but no significant differences were observed between groups. To compare the severity of RDS, only 17.6% of moderate to severe RDS in the control group was found, whereas 100% was found in the study group. Moderate to severe BPD cases were found more often in the control group (70.6%) than in the study group (61.6%), but no statistically significant difference was shown. The immediate complications, e

  7. The effect of alginate and hyaluronate on the viability and function of immunoisolated neonatal rat islets. (United States)

    Velten, F; Laue, C; Schrezenmeir, J


    Recent observations suggest that the extracellular matrix plays a role as regards the viability and morphological integrity in long-term culture of Langerhans islets. For the present study we encapsulated neonatal rat islets without extracellular matrix (WEM), with alginate solution (AL) and with hyaluronate solution (HY) into cuprophane hollow fibers. Function was tested after week 1 and 5. The insulin release of WEM encapsulated islets decreased significantly during the culture period. In contrast to this, AL and HY embedded islets had stable secretion values throughout the whole cultivation. Histological examination confirmed that viability of HY and of AL embedded islets differed significantly from that of WEM encapsulated islets. Furthermore, HY seems to be a more advantageous environment to immunoisolated islets than AL. Both the insulin secretion values and the viability of HY embedded islets were higher than of AL embedded islets. We conclude that an extracellular matrix is important for immunoisolated islets, to maintain their function and morphological integrity and that HY is especially suitable for this application.

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

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    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. Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum. (United States)

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


    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.

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

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    Junko Kimura-Kuroda


    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.

  11. Antiapoptotic Actions of Methyl Gallate on Neonatal Rat Cardiac Myocytes Exposed to H2O2

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    Sandhya Khurana


    Full Text Available Reactive oxygen species trigger cardiomyocyte cell death via increased oxidative stress and have been implicated in the pathogenesis of cardiovascular diseases. The prevention of cardiomyocyte apoptosis is a putative therapeutic target in cardioprotection. Polyphenol intake has been associated with reduced incidences of cardiovascular disease and better overall health. Polyphenols like epigallocatechin gallate (EGCG can reduce apoptosis of cardiomyocytes, resulting in better health outcomes in animal models of cardiac disorders. Here, we analyzed whether the antioxidant N-acetyl cysteine (NAC or polyphenols EGCG, gallic acid (GA or methyl gallate (MG can protect cardiomyocytes from cobalt or H2O2-induced stress. We demonstrate that MG can uphold viability of neonatal rat cardiomyocytes exposed to H2O2 by diminishing intracellular ROS, maintaining mitochondrial membrane potential, augmenting endogenous glutathione, and reducing apoptosis as evidenced by impaired Annexin V/PI staining, prevention of DNA fragmentation, and cleaved caspase-9 accumulation. These findings suggest a therapeutic value for MG in cardioprotection.

  12. Effect of neonatal hypothyroidism on carbohydrate metabolism, insulin secretion, and pancreatic islets morphology of adult male offspring in rats. (United States)

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


    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.

  13. Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups. (United States)

    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


    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 associated metabolic imbalances in rat pups. Pups received one of three treatments from postnatal days 5 to P9: Neonatal Stress (Stress; n=20) = painful stimulus and hypoxic/hyperoxic challenge during 60 min of maternal separation; MTS (n=20) = neonatal stress+10 min of MTS; or Control (n=20). Body weight, DXA whole body fat mass (g), MRI subcutaneous and visceral adipose tissue, and fasting adiponectin, leptin, glucose, insulin, and corticosterone were measured at weaning (P21). Stress and MTS weight gain (g/d) were accelerated following neonatal stress with greater fat mass, abdominal subcutaneous adipose tissue, serum adiponectin, leptin, and fasting glucose at weaning (P21). Male Stress and MTS pups had greater visceral adipose tissue depot. Male and female Stress pups were hyperinsulinemic. In summary, neonatal stress compromised body composition by increasing fat mass and abdominal subcutaneous adipose tissue depot, and in males, visceral adipose tissue depot. Importantly, MTS prevented hyperinsulinemia despite of stress-induced adiposity. We conclude that MTS during neonatal stress has the potential to minimize metabolic consequences associated with stress-driven perturbations in fat mass and abdominal adipose depots. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Effect of electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn and spinal c-fos expression in neonatal, juvenile and adult rats. (United States)

    Wu, Jiang; Hu, Qisheng; Huang, Deying; Chen, Xueling; Chen, Jie


    To explore the response to nociceptive stimuli in spinal cord of immature rat and observe the electrical stimulation of the sciatic nerve on synaptic plasticity of the spinal dorsal horn and spinal c-fos expression in rats of different ages, MK-801 was added to the spinal cord of rats, and the resulting changes in field potential as well as c-fos expression were recorded. LTP in neonatal rats was mainly evoked by A-type nerve fibers, whereas LTP in juvenile and adult rats was mainly evoked by C-type nerve fibers. C-fos expression was significantly increased in the superficial and deep layers of the spinal dorsal horn and in the ventral horn in neonatal rats indicating that the pain signal changed with age. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  15. Fertility potential of male albino rats (Wistar strain) treated with ...

    African Journals Online (AJOL)

    streptomycin combination. ... significant decrease (P<0.05) in the sperm motility of group B rats at 7 days post-treatment with hyper-dose of PSC and the total sperm abnormalities was significantly higher (P<0.05) in the same group of rats compared to A ...

  16. Glucose Homeostasis and Sympathoadrenal Activity in Mercaptoacetate-Treated Rats

    NARCIS (Netherlands)

    Dijk, Gertjan van; Scheurink, Anton; Ritter, Sue; Steffens, Anton

    The effect of the fatty acid oxidation inhibitor, sodium mercaptoacetate (MA, 600 µmol/kg) on peripheral energy substrate metabolism was investigated in rats with permanent heart catheters. Rats were either fed, 48-h food deprived, or exercising for 30 min. Before and after intravenous MA injection,

  17. 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

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    A.C.S. Rezende


    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.

  18. Postnatal thyroid hormone supplementation rescues developmental abnormalities induced by congenital-neonatal hypothyroidism in the rat retina. (United States)

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


    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.

  19. Gypenosides Protected the Neural Stem Cells in the Subventricular Zone of Neonatal Rats that Were Prenatally Exposed to Ethanol

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    Lun Dong


    Full Text Available Fetal alcohol spectrum disorder (FASD can cause severe mental retardation in children who are prenatally exposed to ethanol. The effects of prenatal and early postnatal ethanol exposure on adult hippocampal neurogenesis have been investigated; however, the effects of prenatal ethanol exposure on the subventricular zone (SVZ have not. Gypenosides (GPs have been reported to have neuroprotective effects in addition to other bioactivities. The effects of GPs on neural stem cells (NSCs in the FASD model are unknown. Here, we test the effect of prenatal ethanol exposure on the neonatal SVZ, and the protection potential of GPs on NSCs in FASD rats. Our results show that prenatal ethanol exposure can suppress the cell proliferation and differentiation of neural stem cells in the neonatal SVZ and that GPs (400 mg/kg/day can significantly increase the cell proliferation and differentiation of neural stem cells inhibited by ethanol. Our data indicate that GPs have neuroprotective effects on the NSCs and can enhance the neurogenesis inhibited by ethanol within the SVZ of neonatal rats. These findings provide new evidence for a potential therapy involving GPs for the treatment of FASD.

  20. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs. (United States)

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


    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.

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


    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.

  2. The Effect of Iron Deficiency on Osmotic Sensitivity of Red Blood Cells from Neonatal Rats and Their Mothers. (United States)

    Al-Hashimi, L Mossa; Gambling, Lorraine; McArdle, H J


    Iron deficiency during pregnancy has many effects on both the mother and her developing foetus. These can be both short and long term. One effect is an alteration in fatty acid metabolism and we hypothesised that these changes may result in alterations in membrane function and structure. In order to test this hypothesis, we measured osmotic sensitivity in red blood cells isolated from neonates and their mothers at different times following birth. We fed female rats control or iron-deficient diets for 4 weeks prior to mating and kept them on the same diet until term. At that time, we returned one group of deficient dams to the control diet. The others were kept on the same diet. We showed that iron deficiency results in a decrease in osmotic sensitivity in the mothers but not in their neonates. Returning the dams to the control diet resulted in a return of their red cell osmotic sensitivity to control levels. In the neonates, there was no recovery in haematocrit or in any other parameter, though they did not get any worse, in contrast to the pups being suckled by deficient mothers. The data show two things. The first is that following birth, the mother restores her own iron stores at the expense of the pups, and secondly, there are differences in properties and sensitivities between red cells from mothers and their neonates. This latter observation cannot be explained by differences in the membrane fatty acid profiles, which were not significantly different.

  3. First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs. (United States)

    Fiocchi, R; D'Elia, E; Vittori, C; Sebastiani, R; Strobelt, N; Eleftheriou, G; Introna, M; Freddi, C; Crippa, A


    The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway. (United States)

    Lai, Zhongmeng; Zhang, Liangcheng; Su, Jiansheng; Cai, Dongmiao; Xu, Qingxiu


    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.

  5. Neonatal food restriction and binaural ear occlusion interfere with the maturation of cortical motor pyramids in the rat. (United States)

    Torrero, Carmen; Regalado, Mirelta; Perez, Esther; Rubio, Lorena; Salas, Manuel


    Golgi-Cox-impregnated pyramidal neurons of layer five motor cortical area were investigated in control, binaural ear-occluded control, undernourished and binaural ear-occluded undernourished Wistar rats of 12, 20 and 30 days of age. In neonatally undernourished, binaural ear-occluded-undernourished and partly in ear-occluded-control subjects, there were significant reductions in both the number and extent of the distal part of the dendritic branches of motor pyramids compared to their controls. Moreover, minimal effects on perikarya measurements were observed. These findings suggest that neonatal undernutrition and the concurrent reduction of auditory cues affect dendritic arbor development and possibly the convergence of the auditory experience upon motor pyramids and may interfere with the neocortical modulation of postural and movements activities.

  6. The role of neonatal NMDA receptor activation in defeminization and masculinization of sex behavior in the rat. (United States)

    Schwarz, Jaclyn M; McCarthy, Margaret M


    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.

  7. Radiologic observations in severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant

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    Mortensson, W.; Noack, G.; Curstedt, T.; Herin, P.; Robertson, B.

    Ten newborn babies with severe respiratory distress syndrome, all dependent on artificial ventilation, were treated via the airways with the isolated phospholipid fraction of bovine or porcine surfactant. After treatment with surfactant at a median age of 10.5 h, there was in all patients a striking improvement of lung aeration in chest films, with a decrease in parenchymal fluid retention and in distension of bronchioli. These radiologic findings were associated with a dramatic improvement of oxygenation and a significant reduction of the right-to-left shunt. In spite of the rapid therapeutic response, four patients died from cerebral hemorrhage. One of the surviving patients developed bronchopulmonary dysplasia. Our findings document efficacy of this new surfactant preparation in the neonatal respiratory distress syndrome, but the long-term effects need to be further tested in randomized clinical trials.

  8. Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats. (United States)

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


    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 < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean DeltaAUC values were: 0.17 +/- 0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/- 0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and 0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared

  9. Endothelin-1–Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups (United States)

    Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H.


    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

  10. The protective effect of picroside II against hypoxia/reoxygenation injury in neonatal rat cardiomyocytes. (United States)

    Meng, Fan-Ji; Hou, Zhi-Wen; Li, Yang; Yang, Ying; Yu, Bo


    Picroside II, an iridoid glucoside found in the root of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to possess potent antioxidant activity. However, whether picroside II has a protective effect against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury is poorly understood. To explore the cardioprotective role of picroside II against oxidative stress induced by H/R injury in neonatal rat cardiacmyocytes. The viability and cellular damage of cardiomyocytes were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the levels of reduced (GSH) and oxidized glutathione (GSSG), and the contents of malondialdehyde (MDA) were determined by a colorimetric method. The levels of intracellular reactive oxygen species (ROS) and calcium were evaluated by flow cytometric analysis. We analyzed the effective half-maximal concentration for protection from the dose-response curves and obtained the concentration of 50 µg/mL as EC(50). Pretreated cardiomyocytes with picroside II (50-200 µg/mL), prior to H/R exposure, inhibited LDH activity in culture media and increased cell viability in a dose-dependent manner. This protective effect was accompanied by significantly increasing reduced GSH contents and the activities of SOD and GSH-Px and attenuating MDA and GSSG contents in response to H/R injury. Furthermore, treatment with picroside II also inhibited ROS production and calcium accumulation in cardiomyocytes. The present study demonstrates that picroside II protects cardiomyocytes against oxidative-stress injury induced by H/R through reduction of ROS production and calcium accumulation and enhancement of the activity of antioxidant defense.

  11. Ethanol Influences on Bax Associations with Mitochondrial Membrane Proteins in Neonatal Rat Cerebellum (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats. (United States)

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


    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.

  14. Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation

    NARCIS (Netherlands)

    M.M.J. van der Vorst (Maria); E.D. Wildschut (Enno); R.J.M. Houmes (Robert Jan); S.J. Gischler (Saskia); J.E. Kist-Van Holthe (Joana); J. Burggraaf (Jacobus); A.J. van der Heijden (Bert); D. Tibboel (Dick)


    textabstractIntroduction: Loop diuretics are the most frequently used diuretics in patients treated with extracorporeal membrane oxygenation (ECMO). In patients after cardiopulmonary bypass (CPB) surgery, the use of continuous furosemide infusion is increasingly documented. Because ECMO and CPB are

  15. Maternal and neonatal dietary intake of balanced n-6/n-3 fatty acids modulates experimental colitis in young adult rats. (United States)

    Reddy, K Vijay Kumar; Naidu, K Akhilender


    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.

  16. [Alternations of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kidney ischemic Injury]. (United States)

    Yang, Fan; Yao, Yu-jia; Xiong, Ying; Yuan, Li-xing; Yu, Bo; Chen, Yong-xiu


    To study the changes of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kindney ischemic injury. To explore the interactions between ADF and G-actin and their relationships with actin cytoskeleton. Twenty-four neonatal rats were used to the experiments due to have the weights from 30 to 40 g respectively. Renal ischemia was induced by clamping the left renal pedicle for different periods of time that was in 10 min or 30 min. The kidneys of normal neonatal rats were functioned as the control group. Two kinds of primary antibodies, which one was rabbit anti-chick ADF antiserum and another was mouse monoclonal G-actin antibody, were used on one same section of kidney tissue. FITC-labeled and TRITC-labeled secondary antibodies were used to identify ADF and G-actin respectively. These samples were examined by using a fluorescene microscope. In control group, ADF and G-actin showed to be diffused in cytoplasm of renal tubular epithelial cell. In ischemic injury group, the distributions of ADF and G-actin were changed significantly to apical region of tubular epithelial cells and the renal tubula lumen. Regardless of the ADF expression to not change but G-actin was increased after kidney ischemia. Under the physiolgical condition, ADF and G-actin got a diffuse distribution in cytoplasm of renal tubular epitbelial cell. However, when the kidney got in ischemia, the distributions of ADF and G-actin were changed significantly to apica region of tubular epithelial cell or the renal tubular lumen.

  17. Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke. (United States)

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


    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.

  18. Antidiabetic and antihypertensive effect of Virgin Argan Oil in model of neonatal streptozotocin-induced diabetic and l-nitroarginine methylester (l-NAME) hypertensive rats. (United States)

    Bellahcen, Said; Hakkou, Zineb; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Mekhfi, Hassane; Aziz, Mohammed; Bnouham, Mohamed


    The goal of this study was to examine the effect of Virgin Argan Oil (VAO) obtained from the fruit of Argania spinosa in a model of type 2 diabetes and hypertensive rats. Neonatal diabetes was induced by a single i.p. injection of streptozotocin (90 mg/kg) 2 days after birth. To induce NO-deficient hypertension, the adult diabetic animals were treated with l-nitroarginine methylester (l-NAME) (30 mg/kg/day) given orally for 21 days. Following treatment with VAO (21 days), the hyperglycemia decreased to 1.3 ± 0.07 g/l compared with 1.92 ± 0.09 g/l (p < 0.01) in the untreated diabetic-hypertensive rats. The simultaneous administration of VAO with l-NAME prevented the increase in blood pressure during the 3 weeks of treatment. Blood pressure remained constant at 131 ± 1 mm Hg after 21 days - vs 157 ± 0.64 mm Hg in untreated animals (p < 0.001). The treatment with VAO to diabetic-hypertensive rats caused a significant increase of hepatic glycogen levels (13.3 ± 1.8 vs 6.34 ± 0.75 mg/g tissue in untreated diabetic-hypertensive control group; p < 0.01). In conclusion, the overall findings indicate that VAO possesses antidiabetic and antihypertensive activity in n-stz/l-NAME rats. This effect may be related to its high content of tocopherols, phenolic compounds, and unsaturated fatty acids.

  19. Laser Photoradiation Therapy For Neonatal Jaundice (United States)

    Hamza, Mostafa; Hamza, Mohammad


    This paper describes our leading experience in the clinical application of laser in the treatment of neonatal jaundice. Currently, the irradiation of jaundiced infants during neonatal life to fluorescent light is the most common treatment of neonatal hyperbilirubinemia. The authors have investigated the photodegradation of bilirubin by laser in vitro and in Gunn rats before embarking on its clinical application in the treatment of jaundice in the new born child. This work was done to study the theraputic effect of laser compared to the currently used phototherapy in the treatment of neonatal jaundice. We selected 16 full term neonates with jaundice to be the subject of this study. The neonates of the study were devided into two groups. The first group was treated with continuous phototherapy . The second group recieved photoradiation therapy with gas laser The laser used was a CW argon-ion laser tuned to oscillate at 488.0 nm wavelength. This wavelength selection was based on our previous studies on the effect of laser irradiation of Gunn rats at different wavelengths. Comparison of the results of both methods of treatment will be reported in detail. The advantages and limitations of laser photoradiation therapy for neonatal jaundice will be discussed.

  20. The Power of Classic Music to Reduce Anxiety in Rats Treated with Simvastatin

    Directory of Open Access Journals (Sweden)

    José Geraldo Pereira da Cruz


    Full Text Available Introduction: This study was designed to investigate the effects of music in Wistar rats after sub-chronic treatment of simvastatin. The rats were orally administered with either simvastatin or saline (controls. After 4 weeks of drug treatment, the rats were selected for behavioral studies. The rats were exposed to music 24 hours before behavioral tests (Mozart’s piano sonata, KV361, Largo. Results: The experiments suggest that exposure to chronic treatment with simvastatin (1 or 10 mg/kg/day reduced anxiety levels in rats when associated with Mozart music in an elevated plus-maze. Discussion: These results indicate that music can serve as an effective adjuvant in rats treated with simvastatin, and that this species could potentially be used in other preclinical models utilizing musical interventions.

  1. Aphrodisiac and Male Sexual Characteristics in Albino Rats Treated ...

    African Journals Online (AJOL)

    The use of plants and herbs to boost libido, induce erection, and as an aphrodisiac agent has been in existence for long. The root of Parquetina nigrescens is one of such acclaimed aphrodisiac but there is no scientific documentation to back this up, thus the need for this study. Eighty male rats were completely randomized ...

  2. Insulin resistance in SD rats chronically treated with ethanol (United States)

    We have previously demonstrated that hepatic insulin signaling is disrupted in Sprague-Dawley (SD) rats fed EtOH-containing diets by total enteral nutrition (TEN). To determine if whole body insulin resistance could be demonstrated in the TEN model, we conducted euglycemic-hyperinsulinemic clamp st...

  3. PIXE analysis of trace metals in aspirin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rinsvelt, H.A.; Sater, R.; Hurd, R.W.; Andres, J.M.


    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  4. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)



    Nov 16, 2011 ... study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD ..... Figure 4. The myocardial fibrosis formation after myocardial ischemia and reperfusion surgery. Pictures on the left were hematoxylin and eosin (H and E) staining results, pictures on the right were ...

  5. PIXE analysis of trace metals in aspirin-treated rats (United States)

    Van Rinsvelt, H. A.; Sater, R.; Hurd, R. W.; Andres, J. M.


    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  6. The effect of eurycoma longifolia jack on spermatogenesis in estrogen-treated rats

    Directory of Open Access Journals (Sweden)

    Norhazlina Abdul Wahab


    Full Text Available INTRODUCTION: There is little data concerning the ability of Eurycoma longifolia Jack (EL to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats. METHODS: Adult male Sprague-Dawley rats weighing 200-250 g were divided into four groups of six rats each. Group A (control was given solvent in the same manner as the treated groups were given EL. Group B was treated with EL (8 mg/kg body weight orally. Group C was treated with estradiol (E2 (intramuscular dose of 500 μg/kg body weight, and group D received a combined treatment of oral EL and intramuscular E2. After fourteen consecutive days of treatment, rats from all groups were sacrificed and subjected to spermatogenic and epididymal sperm cell counts. RESULTS: The spermatogenic cell count in the E2-treated group was significantly decreased as compared to the control (p < 0.05 and EL+E2-treated groups (p < 0.05. A similar finding was found for the epididymal sperm count; the E2-treated group had a significant decrease in the count compared to the control (p < 0.05 and EL+E2-treated groups (p < 0.05. Rats that were treated with EL alone exhibited significantly higher sperm counts and sperm motility when compared to the control group (p < 0.05. CONCLUSIONS: EL extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment.

  7. Effect of mancozeb-treated lettuce ( Lactuca sativa ) on wistar rat liver

    African Journals Online (AJOL)

    Because mancozeb, ethylene bis-dithiocarbamate, is mainly used, more than five times, during the growth of lettuce (Lactuca sativa), the aim of the present investigation is to evaluate the potential effect of mancozeb-treated lettuce on the rat liver physiology. Mancozeb-treated lettuce and two doses of mancozeb were ...

  8. Prepubertal testosterone treatment of neonatally gonadectomized male rats: defeminization and masculinization of behavioral and endocrine function in adulthood. (United States)

    Bloch, G J; Mills, R


    Testosterone (T) administered well after the neonatal "critical" period to females at a dose approximating male levels permanently defeminizes reproductive function (see companion publication). To obtain comparable data for the male, neonatally gonadectomized (NeoGx) males received T filled or empty Silastic capsules during days 15-30 of age and were studied in adulthood. Compared to controls, the T treatment resulted in reduced lordosis and proceptive behaviors, increased mounting and intromission behaviors without differences in penile reflexes or size, and reduced plasma FSH and LH surges. Twenty of twenty-three sham-NeoGx males, but only one NeoGx male, showed ejaculatory behavior despite equivalence in penile reflexes and size after detaching a frenulum when present on the penis. These results show that T can still act on neural substrates well beyond the neonatal period to defeminize and masculinize endocrine and behavioral function in the male rat. A comparison with effects in females indicates a sex difference, the male appearing to be more sensitive to these actions of T.

  9. Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior and binding of NMDA receptors in pre-pubertal rats. (United States)

    Flores, G; Ibañez-Sandoval, O; Silva-Gómez, A B; Camacho-Abrego, I; Rodríguez-Moreno, A; Morales-Medina, J C


    In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX) on behavioral paradigms related to olfaction such as exploratory behavior, locomotor activity in a novel environment and social interaction. We also studied the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors during development. The behavioral effects of nOBX (postnatal day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain regions associated with the olfactory circuitry. A significant increase in the novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested post-pubertally failed to habituate to the novel situation as quickly as the sham- and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in nOBX rats compared with sham-operated and normal controls, while normal exploratory behavior was observed between groups in adulthood. In contrast, social interaction was increased in post-pubertal animals that underwent nOBX. Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre-pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex and outer layer of the cingulate cortex. At post-pubertal age, no significant differences in [(125)I]MK-801 binding were observed between groups at any of the brain regions analyzed. These results suggest that nOBX produces pre-pubertal behavioral disturbances and NMDA receptor changes that are transitory with recovery of olfaction early in adulthood. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Evaluation of a novel delayed-type hypersensitivity assay to Candida albicans in adult and neonatal rats. (United States)

    Thorn, Mitchell; Hudson, Adam W; Kreeger, John; Kawabe, Thomas T; Bowman, Christopher J; Collinge, Mark


    Delayed-type hypersensitivity (DTH) is a T-cell-mediated immune response that may be used for immunotoxicity testing in non-clinical species. However, in some cases DTH assays using T-dependent antigens may be confounded by the production of antibodies to the antigen. The authors have previously modified a DTH assay, initially validated in the mouse, for use in juvenile rats to assess the effect of immunosuppressive drugs on the developing rat immune system. The assay measures footpad swelling induced by subcutaneous footpad injection of Candida albicans (C. albicans) derived-chitosan in rats previously sensitized with C. albicans. Antibodies to chitosan are not produced in this model. However, considerable inter-animal variability inherent in the footpad swelling assay can make it difficult to precisely quantify the magnitude of the immune response and inhibition by immunosuppressants, particularly if complete suppression is not observed. This report describes the development of an ex vivo assay to assess DTH in rats using interferon (IFN)-γ production by splenocytes, obtained from rats sensitized with C. albicans, as the quantifiable measure of the DTH response. Adult and neonatal rats administered dexamethasone (DEX), a known immunosuppressant, exhibited immunosuppression as evidenced by a reduction in ex vivo IFNγ production from splenocytes challenged with C. albicans-derived chitosan. Current data indicate that the ex vivo based DTH assay is more sensitive than the conventional footpad swelling assay due to a lower background response and the ability to detect a response as early as post-natal day (PND) 12. The ex vivo based rat DTH assay offers a highly sensitive and quantitative alternative to the footpad swelling assay for the assessment of the immunotoxic potential of drugs. The increased sensitivity of the ex vivo DTH assay may be useful for identifying smaller changes in response to immunotoxic drugs, as well as detecting responses earlier in animal

  11. Effect of Neonatal Exposure to Poly(Ethylene Glycol-block-Poly(Lactic Acid Nanoparticles on Oxidative State in Infantile and Adult Female Rats

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    Monika Dvořáková


    Full Text Available Our goal was to evaluate the potential health risk of the polymeric NP, poly(ethylene glycol-block-poly(lactic acid (PEG-b-PLA, from the view of redox imbalance of the organism in two different life stages. Female Wistar rats were neonatally administered intraperitoneally with PEG-b-PLA NPs [20 mg/kg of b.w. (PEG20 or 40 (PEG40 mg/kg of b.w.] from postnatal day 4 (PND4 to PND7. We measured antioxidant capacity (TEAC, level of protein carbonyls and lipoperoxides in plasma, activities of catalase, glutathione peroxidase (GPx, and superoxide dismutase (SOD in hemolysates of infantile (sacrificed on PND17 and adult (sacrificed after PND176 rats. Compared to controls, neonatal PEG40 exposure induced a significant TEAC reduction in the infantile rats. Protein carbonyls and lipoperoxide levels were not affected after any dose of PEG-b-PLA NP administration. In adult rats, PEG20 administration caused a significant decrease of protein carbonyl levels compared to controls. In infantile rats, both doses of PEG-b-PLA NP administration increased catalase, Gpx, and SOD activities compared to controls. Surprisingly, in adult rats, the activities of Gpx and SOD decreased significantly after administration of both doses of PEG-b-PLA NPs. Obtained data indicate a possible age-related association between the oxidative status and neonatal PEG-b-PLA NP administration in female rats.

  12. Infant formula supplemented with low protein and high carbohydrate alters the intestinal microbiota in neonatal SD rats. (United States)

    Fan, Wenguang; Tang, Yaru; Qu, Yi; Cao, Fengbo; Huo, Guicheng


    Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula) and last but not least, the diet composition. In the diet composition, protein and carbohydrate are very important for the growth of microbiota, many infant fomulas (different ratio protein/carbohydrate) can regulate the development of gut microbiota by different metabolism. The effect of low-protein, high-carbohydrate infant formula on the establishment of microbiota remains unclear, and the effect of human breast milk on the gut microbiota of the rats has also not been reported. In a 7 d intervention, a total of 36 neonatal SD rats (14 d old) were randomly assigned to the following groups: (1) breast-fed group (A group); (2) low-protein, high-carbohydrate infant formula-fed group (B group); (3) human breast milk-fed group (C group). After 7 days, we selected 6 rats at random from each group to study. Microbial composition in the contents of the large intestines was analysed by Miseq Sequencing. Significantly different (pintestines of breast-fed group from low-protein, high-carbohydrate infant formula-fed and human breast milk-fed rats, but the microbiota of low-protein, high-carbohydrate infant formula-fed group and human breast milk-fed group have high similarity. At the phylum level, the absolute quantity of Bacteroidetes, Firmicutes and Proteobacteria (pmicrobiota profile similar to that for human breast milk-fed neonates. The finding could support a new thinking to develop infant formulas, and provide much more details than what is known previously.

  13. Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats. (United States)

    Zhang, Yong; Lan, Rui; Wang, Jun; Li, Xiang-Yun; Zhu, Deng-Na; Ma, Yun-Zhi; Wu, Ji-Tao; Liu, Zhen-Huan


    Acupuncture attenuates neuronal damages following ischemia. The purpose of the present study was to investigate the beneficial effects of acupuncture on hypoxia-ischemia induced brain damages in neonatal rats. Male postnatal 7 days rats were randomly divided into 3 groups: sham control (sham), hypoxia-ischemia (HI), and HI plus acupuncture treatment (HI+Acu). The rats in HI and HI+Acu groups were submitted to model of neonatal HI, established by occluding the left common carotid artery followed by a 3.5h period of hypoxia (8% O2-92% N2). At 24h after HI, animals were stimulated by acupuncture treatment once a day and the treatment continued during 4 weeks, 5days/week. Behavioral functions, learning and memory ability, and body weight were observed at different time-points after HI. DNA fragmentation assay were performed with TUNEL staining to evaluate apoptosis and expression levels of mitochondrial Bcl-2, mitochondrial Bax, Cleaved caspase 3, Cleaved caspase 9 in the damaged hippocampus were detected by western blotting 28 days following HI. GDNF, BDNF levels in hippocampus were also determined. The results showed that acupuncture significantly promoted growth and development, improved neurobehavioral function, learning and memory ability after 20 days' treatment. Furthermore, we obtained one interesting finding that acupuncture attenuated cellular apoptosis and up-regulated GDNF and BDNF levels in hippocampus. All of these results suggest that acupuncture as a potential treatment may exert neuroprotective effects via inhibiting cellular apoptosis, increased GDNF and BDNF expression levels in rat hippocampus experiencing HI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide. (United States)

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


    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

  15. Methylmercury chloride induces learning deficits in prenatally treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Muesch, H.R.; Bornhausen, M.; Kriegel, H.; Greim, H.


    Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 x 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.

  16. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis (United States)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta


    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (pinduced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (pinduced osteoporosis, resembling that of healthy rats.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Effect of testosterone on the proliferation and collagen synthesis of cardiac fibroblasts induced by angiotensin II in neonatal rat. (United States)

    Yang, Xiaocun; Wang, Ying; Yan, Shuxun; Sun, Lina; Yang, Guojie; Li, Yuan; Yu, Chaonan


    The objective is to explore the effect of testosterone on the proliferation and collagen synthesis of neonatal rat cardiac fibroblasts (CF) induced by Angiotensin II (Ang II) and the underlying mechanisms. Derived from neonatal rats, the CFs were divided into 4 groups: the control group, Ang II group, testosterone group, and testosterone + Ang II group in vitro. Cell cycle distribution, collagen counts, and phosphorylated extracellular signal-regulated kinase (ERK1/2) (p - ERK1/2) expression were assessed by flow cytometry, VG staining, and immunocytochemistry, respectively. The Ang II group had a much higher proportion of cells in the S-phase, higher collagen contents, and a higher p - ERK1/2 expression level than either the control or testosterone group. However, these factors were significantly reduced in the testosterone + Ang II group as compared to the Ang II group. In terms of cells in the S-phase and the collagen contents, there was not a significant difference between the testosterone group and the control. However, the protein expression of p-ERK1/2 was significantly increased in the testosterone group as compared to the control. Testosterone inhibits the proliferation and collagen synthesis of CF induced by Ang II. The underlying mechanism may involve the ERK1/2 signaling pathway.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. The cytoskeleton of digitonin-treated rat hepatocytes.


    Fiskum, G; Craig, S W; Decker, G L; Lehninger, A L


    Treatment of isolated rat hepatocptes with low concentrations of digitonin increases the permeability of the plsma membrane to cytosolic proteins without causing release of organelles such as mitochondria into the surrounding medium. Electron microscopy showed that treatment of the cells with increasing concentations of digitonin results in a progressive loss in the continuity of the plasma membrane, while most other aspects of cellular morphology remain normal. Depletion of background staini...

  1. 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


    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.

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

  3. Evaluation of evidence for pharmacokinetics-pharmacodynamics-based dose optimization of antimicrobials for treating Gram-negative infections in neonates

    Directory of Open Access Journals (Sweden)

    Nusrat Shafiq


    Interpretation & conclusions: There is a wide knowledge gap for determining the doses of antimicrobials used for Gram-negative infections in neonates. A different profile of newborns in the developing countries could affect the disposition of antimicrobials for Gram negative infections, necessitating the generation of PK-PD data of antimicrobials in neonates from developing countries. Further, guidelines for treatment of neonatal conditions may incorporate the evidence-based PK-PD-guided dosing regimens.

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

    Directory of Open Access Journals (Sweden)

    Ruibin Zhao


    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.

  5. Neonatal exposure of rats to antidepressants affects behavioral reactions to novelty and social interactions in a manner analogous to autistic spectrum disorders. (United States)

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


    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.

  6. 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


    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.

  7. Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Neves Girardi


    Full Text Available Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h or not from their dams, to a stress challenge (i.p. saline injection. Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze, social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45. Maternally deprived rats exhibited increased plasma corticosterone levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of maternal deprivation, was associated with increased anxiety-like behavior in the elevated plus maze and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of maternal deprivation, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the maternal deprivation paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.

  8. Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide. (United States)

    Jung, Jin Woo; Lee, Mi Suk; Choi, Hyo-Jung; Jung, Sunhee; Lee, Yu-Jung; Hwang, Geum-Sook; Kwon, Tae-Hwan


    In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg·day(-1)·rat(-1) of furosemide. Vehicle-treated (n = 14) and furosemide-treated (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g·220 g body wt(-1)·day(-1) for each rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mosmol/kgH2O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by ultraperformance liquid chromatography coupled with quadrupole time-of-flight (TOF) mass spectrometry, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetylcarnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI-TOF/TOF and IMS. Their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Carnitine compounds were increased in COR and IM, whereas carnitine and acetylcarnitine were decreased in OM. Choline compounds were increased in COR and OM but decreased in IM from furosemide rats. Betaine and GPC were decreased in OM and IM. Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. Copyright © 2016 the American Physiological Society.

  9. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats. (United States)

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M


    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  10. 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


    as striatal input and output areas, including large parts of the cortex. In both species, rAAV5 resulted in a more widespread transgene expression compared to rAAV1. In neonatal rats, rAAV5 also transduced several other areas such as the olfactory bulbs, hippocampus, and septum. Phenotypic analysis of the GFP...

  11. Can information on the gastrointestinal absorption of actinide elements by neonatal rats, guinea pigs, dogs and swine be extrapolated to man

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, M.F.; Gorham, L.S.


    Administration of /sup 238/Pu nitrate to piglets results in absorption that is 1000 times the adult value but neonatal dogs, guinea pigs and rats absorb only 100 times more /sup 238/Pu than adults. Neonatal pigs and rats retain as much as 60% of the dose in the gut mucosa for several days but dogs and guinea pigs retain much less. We have also found this difference in GI tract /sup 238/Pu retention to occur after inhalation, indicating that the gut is an important route of entry for actinides that are inhaled by neonates. Although retention of different gavaged actinides by suckling rats is within the same range (1-3%) we found retention by piglets to range between 35% for /sup 233/U and about 2% for /sup 237/Np, /sup 244/Cm and /sup 241/Am nitrate. While the GI tract of the human infant is probably not nearly as permeable to macromolecules as that of the swine, it is known to be more permeable to macromolecules than that of the adult human. If actinide absorption is also increased in the child, the retention of these elements would probably be more like that in swine than in rats, because of the greater similarity between man and swine in skeletal maturation, in retention of actinides in liver and their longer life span. These studies suggest a need for further information on neonatal absorption of actinides in a large animal species that has a developing GI function more similar to that of humans.


    A, Güllü; S, Dede


    TQ has been used as treatment and preventive agent for many diseases over the years. The goal of this study was to investigate the effects of TQ supplement on fractions of serum proteins. Fourteen male Wistar-Albino rats (200-250 g weight) were used as material for two groups; (control (C) and thymoquinone (TQ) respectively. Each group contained seven rats. The control group had only corn oil, while the TQ group was dissolved in corn oil. 30 mg/kg/day were given by oral gavage for four weeks. The serum protein fractions were identified using cellulose acetate technique. The total protein level and albumin, α-1, α-2 fractions and A/G ratio have showed no difference between groups (p>0.05). β-globulin fractions of TQ group were higher than control's (p<0.05). In addition, it was observed that the γ-globulin levels of TQ group were lower than that of the control group's (p<0.05). From the results, it was observed that the changes of these fractions may have originated from elevation or decline synthesis, or activities of containing proteins.

  13. Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease (United States)

    Jobe, Alan H.


    Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD. PMID:26301222

  14. Asymmetrical development of the monoamine systems in 2,4-dichlorophenoxyacetic acid treated rats. (United States)

    Bortolozzi, Analía; Duffard, Ricardo; de Duffard, Ana María Evangelista


    respect to the left side in striata and accumbens nuclei in T2 female rats supporting the behavioral rotation previously registered by us in these rats. In addition, the increased 5-HT content detected in both the right and left striata observed in this study could be the answer to the behaviors observed and to the early alterations in dopamine in basal ganglia by 2,4-D in neonatal exposed rats, mediated by a serotonergic modulation on the dopaminergic system.

  15. cerebellar parameters in developing 15 day old rat pups treated

    African Journals Online (AJOL)

    There was significant decrease (P<0.05) in the mean neuron/neuroglia ratio in the intracerebellar nuclei, mean numerical density and mean total number of granule cells and reduction in the mean ratio of total number of granule/Purkinje cells in the treated group compared with control. The linear regression comparison for ...

  16. Heat-treated (in single aliquot or batch) colostrum outperforms non-heat-treated colostrum in terms of quality and transfer of immunoglobulin G in neonatal Jersey calves. (United States)

    Kryzer, A A; Godden, S M; Schell, R


    The objective of this randomized clinical trial was to describe the effect on colostrum characteristics and passive transfer of IgG in neonatal calves when using the Perfect Udder colostrum management system (single-aliquot treatment; Dairy Tech Inc., Greeley, CO) compared with a negative control (fresh refrigerated or fresh frozen colostrum) and a positive control (batch heat-treated colostrum). First-milking Jersey colostrum was pooled to achieve 31 unique batches with a minimum of 22.8 L per batch. The batch was then divided into 4 with 3.8 L allocated to each treatment group: (1) heat-treated in Perfect Udder bag at 60°C for 60 min and then stored at -20°C (PU); (2) heat-treated in a batch pasteurizer (Dairy Tech Inc.) at 60°C for 60 min and then stored at -20°C in Perfect Udder bag (DTB; positive control); (3) fresh frozen colostrum stored at -20°C in Perfect Udder bag (FF; negative control); and (4) fresh refrigerated colostrum stored at 4°C in Perfect Udder bag (FR; negative control). Colostrum from all treatments was sampled for analysis of IgG concentration and bacterial culture immediately after batch assembly, after processing, and before feeding. Newborn Jersey calves were randomly assigned to be fed 3.8 L of colostrum from 1 of the 4 treatment groups. A prefeeding, 0-h blood sample was collected, calves were fed by esophageal tube within 2 h of birth, and then a 24-h postfeeding blood sample was collected. Paired serum samples from 0- and 24-h blood samples were analyzed for IgG concentration (mg/mL) using radial immunodiffusion analysis. The overall mean IgG concentration in colostrum was 77.9 g/L and was not affected by treatment. Prefeeding total plate counts (log10 cfu/mL) were significantly different for all 4 treatments and were lower for heat-treated colostrum (PU=4.23, DTB=3.63) compared with fresh colostrum (FF=5.68, FR=6.53). Total coliform counts (log10 cfu/mL) were also significantly different for all 4 treatments and were lower for

  17. Cortical and hippocampal EEG effects of neurotransmitter agonists in spontaneously hypertensive vs. kainate-treated rats. (United States)

    Vorobyov, Vasily; Schibaev, Nikolai; Kaptsov, Vladimir; Kovalev, Georgii; Sengpiel, Frank


    To analyze mediatory mechanisms underlying attention-deficit hyperactivity disorder (ADHD) and their association with epilepsy, the electroencephalogram (EEG) responses to various centrally applied neurotransmitter agonists were studied in spontaneously hypertensive (SH), kainate-treated (KA), and normotensive (control) rats, with chronically implanted electrodes into the frontal cortex and hippocampus and a cannula into the lateral cerebral ventricle. In SH rats, the baseline EEG showed increased delta and beta2 activity in the hippocampus and decreased alpha/beta1 activity in both brain areas. In KA rats, these delta and alpha/beta1 effects were observed 2 weeks post-kainate, while the beta2 activity increase occurred after 5 weeks in the hippocampus and, to a greater extent, 9 weeks post-injection in both brain areas. In SH rats, NMDA increased delta and decreased alpha/beta1 activity, similar to KA rats 5 weeks post-injection. In SH rats, clonidine augmented theta/beta2 increase in the cortex and alpha suppression in both brain areas, in parallel with induction of beta2 activity in the hippocampus. These beta2 effects were observed 5 and 9 weeks post-kainate. In SH rats, baclofen produced robust delta/theta enhancement and alpha/beta1 suppression in both brain areas, with additional beta2 activity increase in the hippocampus, while muscimol was ineffective in both groups of rats. In KA rats, EEG responses to GABA agonists were similar to those in control. Our results demonstrate sensitization of NMDA receptors and α2-adrenoceptors both in SH and KA rats and that of GABAb receptors specifically in SH rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Defeminization of brain functions by a single injection of estrogen receptor α or β agonist in neonatal female rats. (United States)

    Kanaya, Moeko; Yamanouchi, Korehito


    Sexual differentiation of brain function is regulated by estrogen in the perinatal period of rodents. However, the role of the estrogen receptor subtypes ERα and ERβ is still in question. Accordingly, the effects of neonatal treatment with the ERα agonist propyl pyrazole triol (PPT) or the ERβ agonist diarylpropionitrile (DPN) on female reproductive functions were investigated in rats. Female rats were injected subcutaneously with 100-500 µg/10 g body weight (b.w.) PPT or DPN, 100 µg/10 g b.w. estradiol (E(2)), or saline at day 5 (birth day = day 1), and then vaginal opening and vaginal smears were examined. On day 60, their ovaries were removed and lordosis behavior was observed after subcutaneous implantation of a silicon tube containing E(2). As a result, in most PPT and all E(2) rats, vaginal opening was advanced and an irregular estrous cycle was observed. In contrast, in most rats of the DPN groups, vaginal opening was comparable to that of the control and there was a regular estrous cycle. Lordosis tests revealed that the mean lordosis quotients (LQs) in the 250- and 500-µg PPT groups was lower than in the saline group, but higher than in the E(2) group. Mean LQs in all DPN groups were comparable to those in the saline group. These results suggest that ERα plays a major role in masculinization of the system regulating the estrous cycle in the rat brain. In behavioral defeminization of the lordosis-regulation system, ERα was also found to be the main target of estrogen. Copyright © 2012 S. Karger AG, Basel.

  19. Bone repair in rats treated with sodic diclofenac and calcitonin. (United States)

    Sassioto, Maria Cristina Pita; Inouye, Celso Massaschi; Aydos, Ricardo Dutra; Figueiredo, Arthur Silveira de


    To investigate clinical and histologically the bone repair in treated animals with calcitonin and sodic diclofenac. Ninety-six femoral defects were created in forty-eight animals distributed in four groups (n=24): either left untreated, treated with the sodic diclofenac or calcitonin or both. Follow-up was 7, 14 and 21 days. Histological sections stained by haematoxylin-eosin was observed under light microscopy (100X) and quantitatively scored for their trabecular formation. The groups and subgroups were compared being used the Kruskall-Wallis test. Smaller trabecular formation was observed in the animals of the group II and larger trabecular formation in the animals of the group III. Was found significant differences in the comparison between all the groups (Kruskall-Wallis, p sodic diclofenac and accelerated by the calcitonina, when used separately. The associated use of calcitonina and sodic diclofenac didn't show to be the best therapeutic option in the treatment of bone defects surgically created.

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

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    Belinda C. Gómez-Meda


    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.

  1. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside (United States)

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


    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

  2. Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains. (United States)

    Río-Álamos, Cristóbal; Oliveras, Ignasi; Piludu, Maria Antonietta; Gerbolés, Cristina; Cañete, Toni; Blázquez, Gloria; Lope-Piedrafita, Silvia; Martínez-Membrives, Esther; Torrubia, Rafael; Tobeña, Adolf; Fernández-Teruel, Alberto


    The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  3. A retrograde tracing study of compensatory corticospinal projections in rats with neonatal hemidecortication. (United States)

    Yoshikawa, Akira; Atobe, Yoshitoshi; Takeda, Akihito; Kamiya, Yoshinori; Takiguchi, Masahito; Funakoshi, Kengo


    To examine the compensatory mechanisms in rats that underwent left decortication at postnatal day 7 (P7), we injected the retrograde tracers fluorescein isothiocyanate-cholera toxin B subunit (FITC-CTB) and Fast Blue (FB) into the right and left upper cervical spinal cord, respectively, at postoperative weeks 2, 3, 4, and 5 and counted the number of retrogradely labeled corticospinal neurons in the right cerebral cortex compared with that in normally developed rats. Significantly more ipsilaterally projecting neurons were labeled with FITC-CTB in the decorticated rats compared with normal rats at all time points examined. The number of labeled neurons was similar to that at P7 in normal rats. There were also some FITC-CTB and FB double-labeled neurons in both decorticated and normal rats. The number of double-labeled neurons in the decorticated rats increased each week and was significantly greater than that in normal rats at postoperative weeks 4 and 5. The present results suggest that the elimination of ipsilaterally projecting axons observed in normal rats was prevented in the decorticated rats, so that the cerebral cortex neurons on the unlesioned side projected corticospinal tracts to the ipsilateral spinal cord. Furthermore, the collaterals of the corticospinal tracts originating from the cerebral cortex on the unlesioned side also project to the ipsilateral spinal cord. These compensatory mechanisms might underlie the acquisition of motor function in these animals. Copyright © 2012 S. Karger AG, Basel.

  4. [Ultrastructural alterations in colonic mucosa of nifurtimox treated rats]. (United States)

    Montalto de Mecca, M; Rodríguez de Castro, C; Díaz, E G; Castro, J A


    Nifurtimox (Nfx) is a chemotherapeutic agent used in the treatment of acute Chagas' disease. Clinical and experimental studies with this nitroheterocyclic compound evidenced serious undesirable side effects. These were correlated with Nfx nitroreduction to a nitroanion radical followed by superoxide anion generation through a redox cycling process. The aim of this study was to verify whether the oral administration of Nfx to Sprague Dawley male rats (100, p.o.) produced any observable ultrastructural alteration in the cells of the colonic mucosa. Results showed that 24 h after Nfx administration there were observable alterations in this type of cells. They essentially consisted of moderate dilatation of their endoplasmic reticulum and intense dilatation of their Golgi complex. Already 1 and 3 h after Nfx administration, the original compound reached a concentration of 9.7 +/- 2.9 and 7.0 +/- 1.7 nmol.g-1 respectively in the colonic tissue. Studies on Nfx nitroreductase activity of colonic mucosa as determined spectrophotometrically and by HPLC methods showed that the microsomal fraction (from 0.72 +/- 0.29 to 0.26 +/- 0.04 nmol protein) but not the cytosol had the ability to nitroreduce Nfx. The results obtained show a correlation between the ultrastructural localization of injury and that of nitroreductase activity. The intense deleterious effects of Nfx in the Golgi apparatus suggest the potential occurrence of alterations in the synthesis/storage of secretory products of the colonic mucosa.

  5. [Effect of premature birth on retinal vascular development in the neonatal rat]. (United States)

    Yang, Xiang-min; Li, Rong; Wang, Yu-sheng; Chu, Zhao-jie; Gao, Xiang


    To study the effects of premature birth on the development of rat retinal vasculature. Experimental study. Sixty pregnant Sprague-Dawley rats were divided into four groups: bacterial lipopolysaccharide-induced preterm group (LPS group), RU-486 induced preterm group (RP group), cesarean section induced preterm group (CP group), and the normal delivery rats as the control group. The weight of rats from each group was recorded until postnatal day 21. On postnatal day 4, 7, 10 and 14 (P4, P7, P10 and P14), the retina of right eye was dissected and whole-mounted. Each premature group was divided into two subgroups based on the number of rats in each litter, the small subgroup (6-8 rats per litter, group 1) and the large subgroup (14-18 rats per litter, group 2). The development of retinal vascularization process was observed on P4, P7 and P10 (n = 6).Independent t test, one-way ANOVA and LSD-t test were used to analyzed the results. The weight of premature rats in LPS, CP and RP groups was significantly lower than that in the normal group within postnatal 21 days (LSD-t test: all P premature rats have lower weight and much slower rate of early retinal vascularization, as compared with the normal rats. Furthermore, in the premature rats, the proportion of retinal vascularization in larger litters is less than that in smaller litters. These results indicate that premature birth and larger litter size have effects on the development of rat retinal vasculature.

  6. The Lipid Lowering and Cardioprotective Effects of Vernonia calvoana Ethanol Extract in Acetaminophen-Treated Rats

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    Godwin Eneji Egbung


    Full Text Available Background: Paracetamol overdose/abuse as a result of self-medication is a common occurrence amongst people living in low/middle income countries. The present study was designed to investigate the hypolipidemic and cardioprotective potentials of Vernonia calvoana (VC ethanol extract in acetaminophen (paracetamol-treated rats. Methods: Thirty-five Wistar rats weighing 100–150 g were randomly assigned into five groups of seven rats each. Groups 2–5 received high doses of paracetamol to induce liver damage, while group 1 was used as normal control. Afterwards, they were allowed to receive varying doses of VC (group 3 and 4 or vitamin E (group 5, whilst groups 1 and 2 were left untreated. The treatment period lasted for twenty one days after which sera were harvested and assayed for serum lipid indices using standard methods. Results: Groups 3 to 5 treated animals indicated significant decrease (p < 0.001 in low density lipoprotein cholesterol (LDL-c, total cholesterol (TC and triacylglycerol (TG levels relative to the normal and acetaminophen-treated controls, the atherogenic index showed a significant decrease (p < 0.001 in all treated groups compared with normal and acetaminophen-treated controls. However, the VC- and vitamin E-treated groups showed significant (p < 0.001 increase in high density lipoprotein cholesterol (HDL-C relative to the controls. Conclusions: Data from our study suggest that ethanol leaf extract of VC possesses probable hypolipidemic and cardioprotective effects.

  7. Increased DNA damage in blood cells of rat treated with lead as assessed by comet assay

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    Mohammad Arif


    Full Text Available A growing body of evidence suggests that oxidative stress is the key player in the pathogenesis of lead-induced toxicity. The present study investigated lead induced oxidative DNA damage, if any in rat blood cells by alkaline comet assay. Lead was administered intraperitoneally to rats at doses of 25, 50 and 100 mg/kg body weight for 5 days consecutively. Blood collected on day six from sacrificed lead-treated rats was used to assess the extent of DNA damage by comet assay which entailed measurement of comet length, olive tail moment, tail DNA (% and tail length. The results showed that treatment with lead significantly increased DNA damage in a dose-dependent manner. Therefore, our data suggests that lead treatment is associated with oxidative stress-induced DNA damage in rat blood cells which could be used as an early bio-marker of lead-toxicity.

  8. [Effects of AST and ASI on metabolism of free radical in senescent rats treated by HC]. (United States)

    Li, Wei-Zu; Li, Wei-Ping; Yin, Yan-Yan


    To study the effects of Astragaloside (AST) and Astragalus Saponin I (ASI) on metabolism of free radical and immune function in senescent rats treated by HC. Hydrocorisone (HC) was used to estabilsh the aging model in rats. The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine (GSSG) in liver and brain was detected according to kit. The activity of Mn superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit. Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2) production of splenocytes. Compared with HC control, AST and ASI could decrease the content of MDA, GSH and GSSG in liver and brain, increase the activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL-2) activity of splenocytes. AST and ASI could delay the aging effect in rats treated by HC, and its mechanism maybe the antioxidant and regulating immunity.

  9. Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine. (United States)

    Iranloye, B O; Oludare, G O


    Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat.

  10. Predictive score for clinical complications during intra-hospital transports of infants treated in a neonatal unit

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    Anna Luiza Pires Vieira


    Full Text Available OBJECTIVE: To develop and validate a predictive score for clinical complications during intra-hospital transport of infants treated in neonatal units. METHODS: This was a cross-sectional study nested in a prospective cohort of infants transported within a public university hospital from January 2001 to December 2008. Transports during even (n=301 and odd (n = 394 years were compared to develop and validate a predictive score. The points attributed to each score variable were derived from multiple logistic regression analysis. The predictive performance and the score calibration were analyzed by a receiver operating characteristic (ROC curve and Hosmer-Lemeshow test, respectively. RESULTS: Infants with a mean gestational age of 35 + 4 weeks and a birth weight of 2457 + 841 g were studied. In the derivation cohort, clinical complications occurred in 74 (24.6% transports. Logistic regression analysis identified five variables associated with these complications and assigned corresponding point values: gestation at birth [34 weeks (2 pts]; pre-transport temperature [37°C(3pts; 36.3-37.0°C (2 pts]; underlying pathological condition [CNS malformation (4 pts; other (2 pts]; transport destination [surgery (5 pts; magnetic resonance or computed tomography imaging (3 pts; other (2 pts]; and pre-transport respiratory support [mechanical ventilation (8 pts; supplemental oxygen (7 pts; no oxygen (2 pts]. For the derivation and validation cohorts, the areas under the ROC curve were 0.770 and 0.712, respectively. Expected and observed frequencies of complications were similar between the two cohorts. CONCLUSION: The predictive score developed and validated in this study presented adequate discriminative power and calibration. This score can help identify infants at risk of clinical complications during intra-hospital transports.

  11. Evaluation of postpartum behaviour in rats treated with Hypericum perforatum during gestation

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    Vinícius A. Vieira

    Full Text Available Gestational depression is detrimental to the health of the mother and the offspring and contributes to the appearance of depressive and anxiety symptoms during the postnatal period. Traditional antidepressants have undesirable side effects when utilised during gestation, but Hypericum perforatum has been characterised as an efficient and safe antidepressant that prevents the recurrence of symptoms. This study verified the effects of Hypericum perforatumon the behaviour of Wistar rats that were treated during gestation and evaluated 10 and 60 days post-treatment. Pregnant Wistar rats were divided into four groups of ten animals each: one control group that received distilled water and three treatment groups that were treated orally with 36, 72 or 144 mg/kg Hypericum perforatumextract. At 10 and 60 days after parturition and post-treatment, the rats were submitted to the holeboard, the tail suspension, and the forced swim tests. The animals treated with 144 mg/kg Hypericum perforatumexhibited greater head-dipping activity in the hole-board test and reduced immobility in the tail suspension and forced swim tests, suggesting less anxiety and depression 10 and 60 days post-treatment.The results indicated that treating rats with Hypericum perforatumduring the gestational period decreased depressive behaviour and anxiety 10 and 60 days post-treatment.

  12. Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

    NARCIS (Netherlands)

    Schultze, A.E.; Emeis, J.J.; Roth, R.A.


    The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right

  13. PIXE analysis of trace elements in tissues of rats treated with anticonvulsants

    Energy Technology Data Exchange (ETDEWEB)

    Hurd, R.W.; Van Rinsvelt, H.A.; Kinyua, A.M.; O' Neill, M.P.; Wilder, B.J.; Houdayer, A.; Hinrichsen, P.F.


    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  14. Neonatal alcohol impairs the context preexposure facilitation effect in juvenile rats: dose-response and post-training consolidation effects. (United States)

    Jablonski, S A; Stanton, M E


    Alcohol exposure on postnatal days (PND) 4-9 in the rat adversely affects hippocampal anatomy and function and impairs performance on a variety of hippocampus-dependent tasks. Exposure during this developmental window reveals a linear relationship between alcohol dose and spatial learning impairment in the context preexposure facilitation effect (CPFE), a hippocampus-dependent variant of contextual fear conditioning. The purpose of the current report was to examine the effect of a range of alcohol doses administered during a narrower window, PND7-9, than previously reported (Experiment 1) and to begin to determine which memory processes involved in this task are impaired by developmental alcohol exposure (Experiment 2). In Experiment 1, rats pups received a single day binge alcohol dose of either 2.75, 4.00, 5.25 g/kg/day or were sham-intubated (SI) from PND7-9. Conditioned freezing during the test day was evident in all dosing groups, except for Group 5.25 g, indicating no graded dose-related behavioral deficits with alcohol exposure limited to PND7-9. In Experiment 2, rat pups were exposed to the highest effective dose from Experiment 1 (5.25 g/kg/day) or were sham intubated over PND7-9. During training, rats remained in the conditioning context for 5-min following immediate shock delivery. During this test of post-shock freezing, both SI and alcohol-exposed rats given prior exposure to the conditioning context showed comparable freezing levels. Since alcohol-exposed rats showed normal post-shock freezing, deficits by these rats on the test day likely reflect a failure to consolidate or retrieve a context-shock association, rather than a deficit in hippocampal conjunctive processes (consolidation, pattern completion) that occur prior to shock on the training day. These findings illustrate the value of the CPFE for characterizing the separable memory processes that are impaired by neonatal alcohol exposure in this task. Copyright © 2014 Elsevier Inc. All

  15. 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

  16. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats (United States)

    Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim


    Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

  17. Treating perinatal asphyxia with theophylline at birth helps to reduce the severity of renal dysfunction in term neonates. (United States)

    Raina, Alok; Pandita, Aakash; Harish, Rekha; Yachha, Monika; Jamwal, Ashu


    Perinatal asphyxia is a common neonatal problem and contributes significantly to neonatal morbidity and mortality. This study was designed to determine whether theophylline could prevent or ameliorate renal dysfunction in term neonates with perinatal asphyxia. We randomised 159 severely asphyxiated term newborns to receive a single dose of 5 mg/kg intravenous theophylline (n = 78) or a placebo (n = 81) during the first hour of life. The infant's 24-hour fluid intake, urine volume, serum creatinine, creatinine clearance and sodium excretion were recorded during days one, three and five of life, starting 12 hours after the theophylline or placebo infusion. Neonates in the theophylline group had lower serum creatinine levels (0.83 ± 0.35 versus 1.47 ± 0.61; p = 0.00) and higher endogenous creatinine clearance (32.16 ± 16.34 versus 17.73 ± 7.92; p = 0.00) than the placebo group. Severe renal dysfunction, namely acute kidney injury, was present in 36 (15%) of the neonates in the theophylline group versus 117 (48%) in the placebo group (p theophylline administered to term neonates with perinatal asphyxia within the first hour of life significantly decreased serum creatinine levels and significantly increased creatinine clearance. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  18. Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats. (United States)

    Hu, Shufen; Xiao, Ying; Zhu, Liyan; Li, Lin; Hu, Chuang-Ying; Jiang, Xinghong; Xu, Guang-Yin


    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS.

  19. Hydrophilic interaction chromatography-mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

    NARCIS (Netherlands)

    Kok, Miranda G M; Swann, Jonathan R.; Wilson, Ian D.; Somsen, Govert W.; de Jong, Gerhardus J.


    Hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial-host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared

  20. Neonatal Amygdala Lesions and Stress Responsivity in Rats : Relevance to schizophrenia

    NARCIS (Netherlands)

    Terpstra, Jeroen


    "Stress responsiveness in an animal model with relevance to schizophrenia” Rats bearing lesions of the amygdala made on postnatal day 7 (D7 AMX) model aspects of neurodevelopmental psychopathologies, such as schizophrenia. Adult D7 AMX rats display impaired pre-pulse inhibition, impaired

  1. Alpha- and beta-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. fos/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an alpha 1-mediated response

    National Research Council Canada - National Science Library

    K Iwaki; V P Sukhatme; H E Shubeita; K R Chien


    The present study was designed to determine if alpha- and beta-adrenergic stimulation of neonatal rat myocardial cells might induce common and/or distinct members of the immediate early gene program...

  2. Structural Modulation of Gut Microbiota in Rats with Allergic Bronchial Asthma Treated with Recuperating Lung Decoction. (United States)

    Kong, Yan Hua; Shi, Qi; Han, Na; Zhang, Ling; Zhang, Yuan Yuan; Gao, Tong Xin; Chen, Chen; Li, You Lin


    To investigate whether recuperating lung decoction (RLD) can modulate the composition of gut microbiota in rats during asthma treatment. Fifteen Sprague-Dawley rats were divided randomly and equally into control group, model group, dexamethasone (DEX) group, RLD medium-dose group, and RLD high-dose group. The asthma model was established in all groups, except for the control group. The rats in the DEX and RLD groups were treated orally with DEX and RLD, respectively. The rats in the control and model groups were treated orally with 0.9% saline. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification and 454 pyrosequencing. The microbial flora differed between the control and model groups, but the flora in the RLD groups was similar to that in the control group. No significant differences were observed between the RLD high-dose and medium-dose groups. RLD treatment resulted in an increase in the level beneficial bacteria in the gut, such as Lactobacillus and Bifidobacterium spp. Oral administration of RLD increased the number of intestinal lactic acid-producing bacteria, such as Lactobacillus and Bifidobacterium, in asthma model rats. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  3. Chronic morphine and tramadol re-exposure induced an anti-anxiety effect in prepubertal rats exposed neonatally to the same drugs. (United States)

    Gholami, Morteza; Saboory, Ehsan; Khalkhali, Hamid Reza


    Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety-like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3-21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re-exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re-exposure to tramadol and this anxiolytic-like behaviour was more dominant in EPM re-exposure in rats that had received higher doses of tramadol. Re-exposure to tramadol elicited a stronger anxiolytic-like behaviour than re-exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re-exposure to these drugs at an immature stage produces considerable anxiolytic-like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long-term changes in the opioid response. © 2014 Wiley Publishing Asia Pty Ltd.

  4. Spectral heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with cyclooxygenase inhibitors. (United States)

    Dobrek, Łukasz; Baranowska, Agnieszka; Ciesielczyk, Katarzyna; Thor, Piotr J


    The pathogenesis of cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is complex, involving the im- pact of many systemically and locally released agents on autonomic nervous system (ANS) activity, that affects bladder functioning. The purpose of our study was to provide an indirect evaluation of ANS functional status in experimental CP-HC model, involving prostaglandin synthesis block resulting from administration of cyclooxygenase inhibitors. The ANS activity was estimated through the spectral analysis of heart rate variability (HRV) in CP-HC rats divided into three study groups: 1-control, 2-treated with meloxicam (MLX) that preferentially blocks COX-2, and 3-treated with piroxicam (PRX) that inhibits COX1 and 2 activity. In animals treated either with MLX or PRX, the percent distribution of the spectrum in relation to components of very low (VLF) and low (LF) frequency was not different from the control group. PRX-treated group displayed nearly two times lower percent share of the high frequency (HF) component compared to the control. Moreover, an increase of the normalized LF (nLF) value with simultaneous reduction of the normalized HF (nHF) value were noted in PRX-treated rat with no change of these parameters for MLX-treated rats. The HRV analysis in CP-HC rats receiving PRX, indicated a functional reorganization manifested by reduced parasym- pathetic activity and increased sympathetic tonus. A partial prostaglandin synthesis block caused by COX-2 inhibitor (meloxicam) caused no significant changes of evaluated HRV parameters compared to the control. Assessing functional changes of the ANS caused by prostaglandin synthesis block it should be stated that prostaglandins synthesized by the constitutive COX-1 isoform seem to maintain the parasympathetic activity, which may be associated with the cholinergic anti-inflammatory pathway and resolution of inflammation in course of cyclophosphamide-induced cystitis.

  5. Role of HGF-loaded nanoparticles in treating rat acute hepatic failure. (United States)

    Chang, Ren-An; Chen, Zhong; Li, Zhi-Feng


    To explore the role of hepatocyte growth factor (HGF)-loaded polylactic acid-O-carboxymethylated chitosan (PLA-O-CMC) nanoparticles in hepatocyte transplantation (HCT) for treating rat acute liver failure (ALF). Five milliliters of hepatocytes respectively treated with conventional culture (group I), PLA-O-CMC nanoparticles (group II) and HGF-loaded PLA-O-CMC nanoparticles (group III) were transplanted into the abdominal cavities of rat with ALF. In group IV, rats were treated as group II except intravenous 10 pg of HGF daily for 7 days, and in group V, rats were given intraperitoneal RPMI-1640. The survival rate on the 14th day after HCT was higher in groups III IV, and II than in group V (pimproved 24 h after HCT (precovery of hepatic function was the best in group III. In group III, mitotic index was 10.20% on the 5th day after HCT (pnanoparticles can steadily release HGF, and exhibits better tendencies in liver regeneration, survival rate and hepatic function compared with intravenous HGF.

  6. 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


    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.

  7. Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. (United States)

    Brat, Roselyne; Yousef, Nadya; Klifa, Roman; Reynaud, Stephanie; Shankar Aguilera, Shivani; De Luca, Daniele


    Lung ultrasonography (LUS) is a bedside technique useful to diagnose neonatal respiratory problems, but, to our knowledge, no data are available about its use for monitoring lung function or eventually guiding surfactant therapy. To determine the diagnostic accuracy of a neonatal-adapted LUS score to evaluate oxygenation and predict need for surfactant administration. Prospective diagnostic accuracy study following STARD (Standards for the Reporting of Diagnostic Accuracy Studies) guidelines at a tertiary level academic neonatal intensive care unit in 2014. All neonates admitted to the neonatal intensive care unit with signs of respiratory distress were eligible, and 130 neonates were enrolled. The LUS score was calculated in the first hours of life under continuous positive airway pressure. The transcutaneous partial pressure of oxygen (Ptco2) to fraction of inspired oxygen (Fio2) ratio, alveolar-arterial gradient, oxygenation index, and arterial to alveolar ratio were calculated within 30 minutes from LUS, using transcutaneous blood gas monitoring. Surfactant was administered according to 2013 European guidelines. Correlation between LUS score and indices of oxygenation and prediction of surfactant administration. Among the 130 neonates in this study, the LUS score was significantly correlated with all indices of oxygenation, independent from gestational age (GA) (Ptco2 to Fio2 ratio: GA ≥ 34 weeks: ρ = -0.57; GA surfactant better in preterm babies with a GA less than 34 weeks (area under the curve = 0.93; 95% CI, 0.86-0.99; P neonates with a GA of 34 weeks or greater (area under the curve = 0.71; 95% CI, 0.54-0.90; P = .02); the areas under the curve for these 2 GA subgroups are significantly different (P = .02). In babies with a GA less than 34 weeks, a LUS score cutoff of 4 predicted surfactant administration with 100% sensitivity and 61% specificity, yielding a posttest probability of 72%. The LUS score is well correlated with oxygenation status in

  8. Minocycline and Risperidone Prevent Microglia Activation and Rescue Behavioral Deficits Induced by Neonatal Intrahippocampal Injection of Lipopolysaccharide in Rats (United States)

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


    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

  9. Protective effect of chorioamnionitis on the development of bronchopulmonary dysplasia triggered by postnatal systemic inflammation in neonatal rats. (United States)

    Choi, Chang Won; Lee, Juyoung; Oh, Joo Youn; Lee, Seung Hyun; Lee, Hyun Ju; Kim, Beyong Il


    Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model. One microgram of lipopolysaccharide (LPS) or vehicle was injected into the amniotic sacs 2 d before delivery (E20). After birth, 0.25 mg/kg of LPS or vehicle was injected into the peritoneum of pups on postnatal day (P)1, P3, and P5. On P7 and P14, peripheral blood (PB), bronchoalveolar lavage fluid (BALF), and lung tissue were obtained and analyzed. Postnatal i.p. injections of LPS significantly increased neutrophil counts in PB and BALF on P7 and P14. Similarly, proinflammatory cytokine and angiogenic factor transcript levels were increased in the lung by i.p. LPS on P7. Alveolar and pulmonary vascular development was markedly disrupted by i.p. LPS on P14. However, pretreatment with i.a. LPS significantly negated the detrimental effects of postnatal i.p. LPS on PB and BALF neutrophil counts and on lung proinflammatory cytokine expression and histopathological changes. Exposure to early postnatal systemic LPS induces BPD, an arrest in alveolarization, in neonatal rats. Preceding exposure to i.a. LPS protects the lungs against BPD triggered by postnatal systemic inflammation.

  10. 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


    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.

  11. Uric acid plasma level and urine pH in rats treated with ambroxol. (United States)

    Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna


    It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.

  12. Neonatal administration of fluoxetine did not alter the anxiety indicators, but decreased the locomotor activity in adult rats in the elevated plus-maze Administração neonatal de fluoxetina não alterou os indicadores de ansiedade, mas diminuiu a atividade locomotora em ratos adultos no labirinto elevado em cruz

    Directory of Open Access Journals (Sweden)

    Valdenilson Ribeiro Ribas


    Full Text Available The objective of this study was evaluate the anxiety and locomotor activity (LA in 52 Wistar adult male rats, being 26 treated with fluoxetine (10 mg/Kg - sc in the neonatal period. These same rats received foot shock (FS (1.6-mA - 2-s in the 90th day. The anxiety and LA were appraised by plus-maze. The time spent in the open arms was used as anxiety index and the LA was measured by number of entries in closed arms (NECA and the total of entries (TE. T-test was used with pO objetivo deste estudo foi avaliar a ansiedade e a atividade locomotora (AL em 52 ratos Wistar adultos machos, sendo 26 tratados no período neonatal com fluoxetina (10 mg/Kg - sc e no 90º dia, receberam estímulos elétricos nas patas (1,6-mA-2-s. A ansiedade e a AL foram avaliadas por meio do labirinto elevado em cruz. O tempo de permanência dos animais nos braços abertos (BA foi utilizado como índice de ansiedade e a AL medida pelo número de entradas nos braços fechados (NEBF e pelo total de entradas (TE nos BA e BF. O teste t foi utilizado, com (p<0,05 e os dados apresentados em média±erro padrão. Os animais tratados reduziram o NEBF (2,35±0,33 e o TE (3,96±0,61 comparados a seus controles (4,65±0,52 e (6,96±0,94. A administração neonatal de fluoxetina não alterou a ansiedade, mas diminuiu a AL dos animais que receberam EE.

  13. Impaired GABAergic Inhibition in the Prefrontal Cortex of Early Postnatal Phencyclidine (PCP)-Treated Rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe


    in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl...... in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction...

  14. NMR-Based Metabolic Profiling Reveals Neurochemical Alterations in the Brain of Rats Treated with Sorafenib. (United States)

    Du, Changman; Shao, Xue; Zhu, Ruiming; Li, Yan; Zhao, Qian; Fu, Dengqi; Gu, Hui; Kong, Jueying; Luo, Li; Long, Hailei; Deng, Pengchi; Wang, Huijuan; Hu, Chunyan; Zhao, Yinglan; Cen, Xiaobo


    Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs.

  15. Can we Replace Arterial Blood Gas Analysis by Pulse Oximetry in Neonates with Respiratory Distress Syndrome, who are Treated According to INSURE Protocol?

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    Pedram Niknafs


    Full Text Available Neonates with respiratory distress syndrome (RDS, who are treated according to INSURE protocol; require arterial blood gas (ABG analysis to decide on appropriate management. We conducted this study to investigate the validity of pulse oximetry instead of frequent ABG analysis in the evaluation of these patients. From a total of 193 blood samples obtained from 30 neonates <1500 grams with RDS, 7.2% were found to have one or more of the followings: acidosis, hypercapnia, or hypoxemia. We found that pulse oximetry in the detection of hyperoxemia had a good validity to appropriately manage patients without blood gas analysis. However, the validity of pulse oximetry was not good enough to detect acidosis, hypercapnia, and hypoxemia.

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

    DEFF Research Database (Denmark)

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


    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......, whereas the pancreatic insulin content was reduced by 30 % in the rats fed 8.7 % protein. In order to elucidate the mechanism responsible for the attenuation of insulin secretion, measurements were performed of the activity of several islet enzymes that had previously been supposed to be involved...... in the coupling of glucose stimulation to insulin secretion. Islet glucose oxidation was unaffected, but glucose-stimulated hydrolysis of phosphatidylinositol was reduced by one-third in the islets of rats fed 8.7% protein. The activity of mitochondrial glycerophosphate dehydrogenase was similar in islets of rats...

  17. Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity (United States)

    Sulkowski, G. M.; Li, G.-H.; Sajdel-Sulkowska, E. M.


    We have previously reported that the developing rat cerebellum is affected by hypergravity exposure. The effect is observed during a period of both granule and glial cell proliferation and neuronal migration in the cerebellum and coincides with changes in thyroid hormone levels. The present study begins to address the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of cerebellar proteins that are known to be directly involved in cell-cell interactions [protein expressing 3-fucosyl- N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (NCAM-L1)] and those that affect cell-cell interactions indirectly [glial fibrillary acidic protein (GFAP)] in rat neonates exposed to centrifuge-produced hypergravity. Cerebellar mass and protein expression in rat neonates exposed to hypergravity (1.5 G) from gestational day (G) 11 to postnatal day (P) 30 were compared at one of six time points between P6 and P30 against rat neonates developing under normal gravity. Proteins were analyzed by quantitative western blots of cerebellar homogenates prepared from male or female neonates. Cerebellar size was most clearly reduced in male neonates on P6 and in female neonates on P9, with a significant gender difference; differences in cerebellar mass remained significant even when change in total body mass was factored in. Densitometric analysis of western blots revealed both quantitative and temporal changes in the expression of selected cerebellar proteins that coincided with changes in cerebellar mass and were gender-specific. In fact, our data indicated certain significant differences even between male and female control animals. A maximal decrease in expression of CD15 was observed in HG females on P9, coinciding with maximal change in their cerebellar mass. A shift in the time-course of NCAM-L1 expression resulted in a significant increase in NCAM-L1 in HG males on P18, an isolated time at which

  18. Ellagic Acid Increases Osteocalcin and Alkaline Phosphatase After Tooth Extraction in Nicotinic-Treated Rats. (United States)

    Al-Obaidi, Mazen M Jamil; Al-Bayaty, Fouad Hussain; Al Batran, Rami; Ibrahim, Omar Emad; Daher, Aqil M


    -To examine the effect of nicotine (Ni) on bone socket healing treated with Ellagic acid (EA) after tooth extraction in rat. Thirty-Two Sprague Dawley (SD) male rats were divided into four groups. The group 1 was administrated with distilled water intragastrically and injected sterile saline subcutaneously. The group 2 was administrated with EA orally and injected with sterile saline subcutaneously. The groups 3 & 4 were subcutaneously exposed to Ni for 4 weeks twice daily before tooth extraction procedure, and maintained Ni injection until the animals were sacrificed. After one month Ni exposure, the group 4 was fed with EA while continuing Ni injection. All the groups were anesthetized, and the upper left incisor was extracted. Four rats from each group were sacrificed on 14(th) and 28(th) days. Tumour necrosis factor alpha (TNFα), Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6) were applied to assess in serum rat at 14th and 28(th) days. Superoxide dismutase (SOD) and Thiobarbituric acid reactive substances (TBRAS) levels were assessed to evaluate the antioxidant status and lipid peroxidation accordingly after tooth extraction in homogenized gingival maxilla tissue of rat at 14(th) and 28(th) days. The socket hard tissue was stained by eosin and hematoxylin (H&E); immunohistochemical technique was used to assess the healing process by Osteocalcin (OCN) and Alkaline Phosphatase (ALP) biomarkers. Ni-induced rats administered with EA compound (Group 4) dropped the elevated concentration of pro-inflammatory cytokines significantly when compared to Ni-induced rats (Group 3) (pextraction in nicotinic rats could be due to the antioxidant activity of EA which lead to upregulate of OCN and ALP proteins which are responsible for osteogenesis.

  19. Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats. (United States)

    Alzamendi, Ana; Castrogiovanni, Daniel; Ortega, Hugo H; Gaillard, Rolf C; Giovambattista, Andres; Spinedi, Eduardo


    Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

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


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


    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...

  1. Inhibition of NaCl appetite when DOCA-treated rats drink saline. (United States)

    Stricker, Edward M; Bushey, Michael A; Hoffmann, Myriam L; McGhee, Marilyn; Cason, Angela M; Smith, James C


    Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).

  2. Short-term neonatal/prepubertal exposure of dibutyl phthalate (DBP) advanced pubertal timing and affected hypothalamic kisspeptin/GPR54 expression differently in female rats. (United States)

    Hu, Jialei; Du, Guizhen; Zhang, Wei; Huang, Hongyu; Chen, Danni; Wu, Di; Wang, Xinru


    Dibutyl phthalate (DBP) had been widely used and its exposure in children has been thought to be one of the reasons causing a trend of advanced pubertal timing in girls. Puberty starts from hypothalamic gonadotropin-releasing hormone release which is controlled by many factors including neurotransmitter kisspeptin and its receptor GPR54. These neural organization or reorganization happens in hypothalamus during neonatal or prepubertal period which may be two target windows of DBP exposure. The present study was designed to determine: (1) the difference between the effects of neonatal and prepubertal DBP exposure on female pubertal timing; (2) whether kisspeptin/GPR54 expression in hypothalamus would respond to neonatal and prepubertal DBP exposure differently. Female Sprague-Dawley rats were exposed by subcutaneous injection of 0.5, 5 and 50mg/kg DBP during Postnatal day (P)1-5 (neonatal) or P26-30 (prepubertal). Physiological data demonstrated that both neonatal and prepubertal DBP exposure could advance pubertal timing significantly accompanied by irregular estrous cycles but only a little gonadal impairment. Exposure-period-related difference was found significant with prepubertal exposure groups having longer estrous cycle duration, heavier at vaginal opening and having higher serum estradiol level compared with neonatal exposure groups. Molecular data showed an up-regulated trend in kisspeptin mRNA and immunoreactivity levels of hypothalamic area arcuate but a down-regulation in GPR54 mRNA expression after P1-5 DBP treatment. In P26-30 groups, kisspeptin mRNA and immunoreactivity levels tended to be lower after DBP treatment. These results demonstrated small dose of DBP could induce earlier pubertal timing in females and both neonatal and prepubertal periods were critical windows for DBP exposure. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Lipotoxic Palmitate Impairs the Rate of β-Oxidation and Citric Acid Cycle Flux in Rat Neonatal Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Taha Haffar


    Full Text Available Background/Aims: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts. Methods: We measured fatty acid oxidation, acetyl-CoA oxidation, and carnitine palmitoyl transferase (Cpt1b activity. We measured both forward and reverse aconitase activity, as well as NAD+ dependent isocitrate dehydrogenase activity. We also measured reactive oxygen species using the 2', 7'-Dichlorofluorescin Diacetate (DCFDA assay. Finally we used thin layer chromatography to assess diacylglycerol (DAG levels. Results: We found that palmitate significantly impaired mitochondrial β-oxidation as well as citric acid cycle flux, but not Cpt1b activity. Palmitate negatively affected net aconitase activity and isocitrate dehydrogenase activity. The impaired enzyme activities were not due to oxidative stress but may be due to DAG mediated PKC activation. Conclusion: This work demonstrates that palmitate, a highly abundant fatty acid in human diets, causes impaired β-oxidation and citric acid cycle flux in primary neonatal cardiomyocytes. This metabolic defect occurs prior to cell death suggesting that it is a cause, rather than a consequence of palmitate mediated lipotoxicity. This impaired mitochondrial metabolism can have important implications for metabolic diseases such as diabetes and obesity.

  4. Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. (United States)

    Guven, Ahmet; Gundogdu, Gokhan; Vurucu, Sabahattin; Uysal, Bulent; Oztas, Emin; Ozturk, Haluk; Korkmaz, Ahmet


    Necrotizing enterocolitis (NEC) remains a major cause of morbidity and death in neonates. Evidence suggests that an imbalance between activated proinflammatory response with inadequate antiinflammatory protection results in NEC. Ozone has been proposed as an antioxidant enzyme activator, immunomodulator, and cellular metabolic activator. Therefore, this study was designed to investigate whether medical ozone therapy is effective on neonatal rat model of NEC. Thirty-eight newborn Sprague-Dawley pups were randomly divided into 3 groups of NEC, NEC + ozone, and control (left to breast feed). Necrotizing enterocolitis was induced by enteral formula feeding and exposure to 100% carbon dioxide inhalation for 10 minutes after +4 degrees C cold exposures for 5 minutes and 97% oxygen for 5 minutes 2 times daily. The NEC + ozone group received 0.7 mg/kg per day ozone/oxygen mixture intraperitoneally for a total of 3 days after first day of NEC procedure. The pups were killed at fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood sample from pups were also obtained. The mortality rate and the weight loss were significantly higher in NEC group than control and treatment groups. Oxidative stress markers (malondialdehyde and protein carbonyl content) significantly increased and antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) were significantly decreased in NEC group. All these biochemical changes were ameliorated in NEC + ozone group. Nitrate plus nitrite levels and serum tumor necrosis factor alpha were elevated in NEC group and reduced in treatment group. In addition, histopathologic injury score of NEC group was significantly higher than NEC + ozone group. Ozone treatment significantly reduced the severity of NEC by modulating antioxidative defense and antiinflammatory protection in our experimental animal model.

  5. [Effects of bone marrow mesenchymal stem cells on learning and memory functional recovery in neonatal rats with hypoxic-ischemic brain damage]. (United States)

    Liu, Yang; Zhang, Xuan; Dai, Ying; Shu, Chang; Qu, Ping; Liu, You-xue; Yang, Li; Li, Ting-yu


    Neonatal hypoxic-ischemic brain damage (HIBD) causes acute death and chronic nervous system sequelae in newborn infants and children. Whereas there have been no specific treatment towards it up to now. Studies have shown that bone marrow mesenchymal stem cells (MSCs) have the therapeutic potential in many nervous system diseases and the authors previously found that retinoid acid (RA), which plays an important role in brain development, could enhance the neural differentiation of rat MSCs (rMSCs) in vitro. This study aimed to examine effects of rMSCs and RA-preinduced rMSC on learning and memory functional recovery after HIBD in neonatal rats in order to explore a new treatment strategy for clinical application, and explore the mechanism of action of rMSCs. Rat MSCs were isolated and purified from the whole bone marrow of juvenile Wistar rats by removing the non-adherent cells in primary and passage cultures. Neonatal hypoxic-ischemic brain damage rat models were built according to the methods described by Rice: the right carotid artery of 7-day-postnatal Wistar rats was ligated under anesthesia, and then the rats were exposed to 8% - 9% O2 in a container. At 5 days after hypoxia-ischemia, the HIBD neonatal rats were randomly divided into 3 groups and respectively transplanted with saline, BrdU marked rMSCs (1 - 2 x 10(5)) or RA-preinduced rMSCs (1 - 2 x 10(5)) into their lateral cerebral ventricle. Immunohistochemistry for nestin, neuron-specific enolase (NSE), neurofilament protein-heavy chain (NF-H) and glial fibrillary acidic protein (GFAP) were used to identify cells derived from rMSCs at 14 days and 42 days after transplantation. Shuttle box test was performed to evaluate the condition of learning and memory functional recovery when animals were 7 weeks old. Neurotrophin and receptors cDNA microarray were also employed at 14 days after transplantation to investigate the underlying action mechanisms of rMSCs treatment. Real-time PCR was used to confirm some of

  6. Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus : a retrospective study

    NARCIS (Netherlands)

    Koning, Sarah H.; Hoogenberg, Klaas; Scheuneman, Kirsten A.; Baas, Mick G.; Korteweg, Fleurisca J.; Sollie, Krystyna M.; Schering, Bertine J.; van Loon, Aren J.; Wolffenbuttel, Bruce H. R.; van den Berg, Paul P.; Lutgers, Helen L.


    Background: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment-diet-only versus additional insulin therapy-were based on the 2010 national Dutch guidelines. Methods: Retrospective study of the electronic medical

  7. A new measure of hindlimb stepping ability in neonatally spinalized rats. (United States)

    Hillyer, Jessica E; Joynes, Robin L


    One of the most widely used animal models for assessing recovery of locomotor functioning is the spinal rat. Although true differences in locomotor abilities of these animals are exhibited during treadmill testing, current measurement techniques often fail to detect them. The HiJK (Hillyer-Joynes Kinematics) scale was developed in an effort to distinguish more effectively between groups of spinal rats. Scale items were compiled after extensive review of the literature concerning development and analysis of rat locomotion and a thorough examination of the current tools. Treadmill tests for 137 Sprague-Dawley rats were taped and scored. The structure of the scale was tested with principle components and factor analysis, in which six of the eight items accounted for 59% of the variance, while all eight accounted for 78%. Validity tests demonstrate that HiJK is measuring locomotor performance accurately and powerfully. First, the HiJK scale correlates highly (>.8) with the widely used BBB scale and second, as shown with ANOVA, can distinguish between different groups of spinal rats. Reliability of the scale was also analyzed. Cronbach's alpha was shown to be .91, indicating considerable internal consistency. Additionally, inter-rater and intra-rater reliabilities were substantial, with correlations for most items reaching above .80. We believe that the HiJK scale will help researchers verify existing experimental differences, advance the field of spinal cord research, and, hopefully, lead to discovery of methods to enhance recovery of function.

  8. Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine

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    Conceição Aparecida Dornelas

    Full Text Available ABSTRACT Objective: to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. Methods: we divided forty Wistar rats into four groups: group I - control group (Sham; group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. Results: in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000. Conclusion: Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones.

  9. Modulation of oxidative stress by enalapril and valsartan in adrenaline treated rats: a comparative study. (United States)

    Huda, S; Akhter, N


    Angiotensin (Ang II) II is known to promote oxidative stress in acute myocardial infarction (AMI). Inhibition of renin angiotensin system (RAS) or blockade of Ang II receptors may therefore be effective in reducing oxidative stress during AMI. The study evaluates and compares the protective effect of Angiotensin Converting Enzyme (ACE) inhibitor and AT1 receptor blocker in adrenaline induced oxidative stress in rats. Rats were treated with two successive injections of adrenaline subcutaneously at a dose of 2 mg/kg administered 24 hours apart. In other two groups of rats enalapril (30 mg/kg) or valsartan (30 mg/kg) were given orally once daily through intragastric tube for 2 weeks and then two injections of adrenaline were administered 24 hours apart. Serum Aspertate Transaminase (AST), plasma Malonde Aldehyde (MDA), erythrocyte GSH and serum vitamin E levels were measured 24 hours after the 2nd injection of adrenaline in all the groups. Administration of adrenaline caused significant increase (p adrenaline treated rats. However, no significant difference was noted between the effect of enalapril and valsartan on serum AST, plasma MDA, erythrocyte GSH and serum vitamin E levels. It may be concluded that both enalapril and valsartan offered cardioprotection in adrenaline induced oxidative stress, but the protection afforded by valsartan was not superior to enalapril.

  10. Free serum testosterone level in male rats treated with tribulus alatus extracts

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    Walid H. El-Tantawy


    Full Text Available OBJECTIVE: The present study was undertaken to investigate the effect of Tribulus alatus extracts on free serum testosterone in male rats. MATERIALS AND METHODS: Free serum testosterone level was measured in male rats treated with alcoholic extracts of the aerial part without fruits, fruits of Tribulus alatus and their fractions. RESULTS: All tested extracts showed significant increase in the level of free serum testosterone when compared to that of corresponding control, p < 0.05. Statistical comparison of all groups revealed that the maximum level was found in groups treated with chloroformic and ethanolic fractions of fruits extract. CONCLUSION: Tribulus alatus extract appears to possess aphrodisiac activity due to its androgen increasing property.

  11. Biochemical effects in normal and stone forming rats treated with the ripe kernel juice of plantain (musa paradisiaca). (United States)

    Devi, V K; Baskar, R; Varalakshmi, P


    The effect of Musa paradisiaca stem kernel juice was investigated in experimental urolithiatic rats. Stone forming rats exhibited a significant elevation in the activities of two oxalate synthesizing enzymes - Glycollic acid oxidase and Lactate dehydrogenase. Deposition and excretion of stone forming constituents in kidney and urine were also increased in these rats. The enzyme activities and the level of crystalline components were lowered with the extract treatment. The extract also reduced the activities of urinary alkaline phosphatase, lactate dehydrogenase, r-glutamyl transferase, inorganic pyrophosphatase and β-glucuronidase in calculogenic rats. No appreciable changes were noticed with leucine amino peptidase activity in treated rats.

  12. Protective effect of Aplysin on hepatic injury in ethanol-treated rats. (United States)

    Ge, Na; Liang, Hui; Liu, Ying; Ma, Ai-guo; Han, Lei


    This study evaluated the protective effects of Aplysin against ethanol-induced hepatic injury in rats and analyzed the associated mechanisms. Rats were administered orally with ethanol 8-12 ml/kg bw excluding the rats in the control group at 1h after rats were administered by gavage doses of Aplysin (50, 100, and 150 mg/kg bw) every day. After 6 weeks, rats were sacrificed, and liver injury was evaluated by biochemical and pathological examination. Hepatocyte apoptosis was analyzed by annexin V-FITC/PI staining. Ethanol metabolic enzymes, oxidative stress, mitochondrial function, and Bcl-2, Bax, cytochrome c and cleaved caspase-3 expressions were evaluated by western blot analysis. These results demonstrated that Aplysin exhibited a significant hepatoprotective effect. In the ethanol-treated group, cytochrome P4502E1 and alcohol dehydrogenase were increased significantly in liver tissue. Moreover, Aplysin not only significantly reversed the ratio of NAD(+)/NADH and mitochondrial glutathione depletion, but also reversed the decreased activity of mitochondrial respiratory chain complexes I, III and IV. Overexpression of cytoplasmic cytochrome c and caspase-3 activation was suppressed by Aplysin. These results suggest that Aplysin alleviates hepatocyte apoptosis by modulating the ethanol-metabolizing pathway, attenuating oxidative stress, ameliorating mitochondrial function, inhibiting mitochondrial damage-mediated apoptosis, which ultimately prevent and repair alcoholic liver injury. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Anthriscus nemorosa essential oil inhalation prevents memory impairment, anxiety and depression in scopolamine-treated rats. (United States)

    Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian


    Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

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    Solange Maria Magalhães da Silva Porto


    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

  15. Erlotinib preserves renal function and prevents salt retention in doxorubicin treated nephrotic rats.

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    Raed N Bou Matar

    Full Text Available Nephrotic syndrome is associated with up-regulation of the heparin-binding epidermal growth factor (HB-EGF. Erlotinib blocks the activation of the epidermal growth factor receptor (EGFR in response to HB-EGF. This study investigates the effect of Erlotinib on the progression of proteinuria, renal dysfunction, and salt retention in doxorubicin treated nephrotic rats. Male rats were divided into 3 pair-fed groups (n = 13/group as follows: Control rats (Ctrl; rats receiving intravenous doxorubicin (Dox; and rats receiving intravenous doxorubicin followed by daily oral Erlotinib (Dox + Erl. Upon establishment of high grade proteinuria, urine sodium and creatinine clearance were measured. Kidney tissue was dissected and analyzed for γ-epithelial sodium channel (γENaC, sodium-potassium -chloride co-transporter 2 (NKCC2, sodium chloride co-transporter (NCC, aquaporin 2 (AQP2, and EGFR abundances using western blot. Creatinine clearance was preserved in the Dox + Erl rats as compared to the Dox group (in ml/min: Ctrl: 5.2±.5, Dox: 1.9±0.3, Dox + Erl: 3.6±0.5. Despite a minimal effect on the degree of proteinuria, Erlotinib prevented salt retention (Urinary Na in mEq/d: Ctrl: 2.2±0.2, Dox: 1.8±0.3, Dox + Erl: 2.2±0.2. The cleaved/uncleaved γENaC ratio was increased by 41±16% in the Dox group but unchanged in the Dox + Erl group when compared to Ctrl. The phosphorylated EGFR/total EGFR ratio was reduced by 74±7% in the Dox group and by 77±4% in the Dox + Erl group. In conclusion, Erlotinib preserved renal function and prevented salt retention in nephrotic rats. The observed effects do not appear to be mediated by direct blockade of EGFR.

  16. Evaluation of the true precocious puberty rats induced by neonatal administration of Danazol: Therapeutic effects of nourishing "Yin"- removing "Fire" Chinese herb mixture

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    Chen Boying


    Full Text Available Abstract Background Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture, a traditional herb-based formulation, has been successfully used for the management of idiopathic true precocious puberty (IPP for more than thirty years. Precocious puberty rat model by neonatal administration of Danazol was used to investigate the effects of the herb mixture on the advanced sexual development of the rats, and the expression of hypothalamic gonadotropin-releasing hormone (GnRH, which is the important regulator for the hypothalamus-pituitary-gonadal axis, particularly at puberty. Methods Female Sprague-Dawley rats were divided into five groups: intact normal (N, IPP model (M, vehicle with no IPP (V, IPP model exposed to herb mixture (HM and IPP model exposed to saline (S. Rats at 5 days of age were given a single subcutaneous injection of 300 microgram of Danazol dissolved in 25 microliter vehicle of propylene glycol-ethanol (1:1, v/v, to establish the precocious puberty model. From the day 15, rats in HM and S groups were continuously fed with either Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture 2 ml or saline 2 ml, until 3 consecutive regular estrous cycles were established. The day of vaginal opening and the day of setup regular estrous cycle of the rats were observed. Blood concentration of estrogen was determined by radioimmunoassay. Immunohistochemistry and RT-PCR analysis were used to explore the expression of GnRH. Results The day of vaginal opening and first estrous showed significant advancement in M compared with N and V (p Conclusion The true precocious puberty model by neonatal administration of Danazol in female rats showed augmented expression of hypothalamic GnRH; the Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture down-regulated the increased GnRH expression, and significantly delayed the sexual development of the precocious puberty rat.

  17. treated rats

    African Journals Online (AJOL)



    Jan 8, 2014 ... characterized by macrocytic anemia and leucopenia. Our data show statistically significant decreases in total leukocytes count (TLC) in which, hemoglobin concentration (Hb. conc.), packed cell volume. (PCV), and red cell count (RCC), accompanied by significant increases in mean cell volume (MCV), red.

  18. [Comparative evaluation of Leningrad-3 mumps vaccine virus neurovirulence in a neonatal rat model]. (United States)

    Ignat'ev, G M; Otrashevskaia, E V; Rubin, S A


    The neurovirulence and replication potential of several mumps virus strains, including Leningrad-3 mumps vaccine virus (FSUE SIC "Microgen", Russia) and wild type strains isolated in the Novosibirsk Region (Russia), were assessed in rat tests. The mean neurovirulence scores of the Leningrad-3 virus (mumps vaccine strains (usually ranging from 0 to 5). In general, the relative ability of the viruses to replicate in the rat brain tracked with their neurovirulence scores. These results indicate a low neurovirulence potential of the Leningrad-3 mumps vaccine virus for humans.

  19. Acute lesions induced by. cap alpha. -irradiation of intestine after plutonium gavage of neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, P.; Beauvallet, M.; Metivier, H.; Moutairou, K.; Masse, R.


    After gavage of two-day-old rats with /sup 238/Pu(IV)-citrate at 17.4 MBq/kg (122 kBq per animal), 45% of the animals died during the second week following ingestion. Histological analysis showed that death was due to acute intestinal lesions caused by ..cap alpha..-radiation that resulted in denudation of the ileum. Under these experimental conditions, the total ..cap alpha..-dose delivered to the ileal wall and its contents was estimated at 150 Gy. No acute lesions were observed after gavage of two-day old rats with Pu-citrate at 5.3 MBq/kg.

  20. The antioxidant and antigenotoxic effects of pycnogenol(®) on rats treated with cisplatin. (United States)

    Aydin, Birsen; Unsal, Meftun; Sekeroglu, Zulal A; Gülbahar, Yavuz


    Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced toxicity. Pycnogenol® is known for its strong antioxidant and anti-inflammatory effects. In this study, the possible protective effects of pycnogenol on kidney, bone marrow, and red blood cells in rats treated with cisplatin were investigated. The rats were divided into four groups. Group 1 was the control and groups 2, 3, and 4 were orally treated with pycnogenol (200 mg/kg bw, o.p) for 5 days, treated with cisplatin (7 mg/kg bw, i.p.) on the fifth day and treated with cisplatin plus pycnogenol, respectively. Antioxidative parameters in kidney and red blood cells were measured. Chromosome anomalies in bone marrow and renal histopathology were also investigated. Activities of pro-oxidant enzymes (myeloperoxidase and xanthine oxidase), malondialdehyde, and nitric oxide levels significantly increased but antioxidant enzymes activities decreased in the kidneys and red blood cells after cisplatin treatment. Pycnogenol treatment prior to the administration of cisplatin significantly decreased cisplatin-induced injury, as evidenced by its normalizing these parameters. Chromosomal aberrations decreased and mitotic index frequencies increased in bone marrow treated with cisplatin plus pycnogenol. These findings suggest that pycnogenol may be a useful protective agent against the toxicity associated with cisplatin therapy.

  1. 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. (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina


    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.

  2. MicroRNA-210 Suppresses Junction Proteins and Disrupts Blood-Brain Barrier Integrity in Neonatal Rat Hypoxic-Ischemic Brain Injury. (United States)

    Ma, Qingyi; Dasgupta, Chiranjib; Li, Yong; Huang, Lei; Zhang, Lubo


    Cerebral edema, primarily caused by disruption of the blood-brain barrier (BBB), is one of the serious complications associated with brain injury in neonatal hypoxic-ischemic encephalopathy (HIE). Our recent study demonstrated that the hypoxic-ischemic (HI) treatment significantly increased microRNA-210 (miR-210) in the neonatal rat brain and inhibition of miR-210 provided neuroprotection in neonatal HI brain injury. The present study aims to determine the role of miR-210 in the regulation of BBB integrity in the developing brain. miR-210 mimic was administered via intracerebroventricular injection (i.c.v.) into the brain of rat pups. Forty-eight hours after the injection, a modified Rice-Vannucci model was conducted to produce HI brain injury. Post-assays included cerebral edema analysis, western blotting, and immunofluorescence staining for serum immunoglobulin G (IgG) leakage. The results showed that miR-210 mimic exacerbated cerebral edema and IgG leakage into the brain parenchyma. In contrast, inhibition of miR-210 with its complementary locked nucleic acid oligonucleotides (miR-210-LNA) significantly reduced cerebral edema and IgG leakage. These findings suggest that miR-210 negatively regulates BBB integrity i n the neonatal brain. Mechanistically, the seed sequences of miR-210 were identified complementary to the 3' untranslated region (3' UTR) of the mRNA transcripts of tight junction protein occludin and adherens junction protein β-catenin, indicating downstream targets of miR-210. This was further validated by in vivo data showing that miR-210 mimic significantly reduced the expression of these junction proteins in rat pup brains. Of importance, miR-210-LNA preserved the expression of junction proteins occludin and β-catenin from neonatal HI insult. Altogether, the present study reveals a novel mechanism of miR-210 in impairing BBB integrity that contributes to cerebral edema formation after neonatal HI insult, and provides new insights in miR-210-LNA

  3. Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α. (United States)

    Sewing, A Charlotte P; Kantores, Crystal; Ivanovska, Julijana; Lee, Alvin H; Masood, Azhar; Jain, Amish; McNamara, Patrick J; Tanswell, A Keith; Jankov, Robert P


    Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed in human infants with severe bronchopulmonary dysplasia. Inhalation of CO(2) (therapeutic hypercapnia) has been described to limit cytokine production and to have anti-inflammatory effects on the injured lung; we therefore hypothesized that therapeutic hypercapnia would prevent bleomycin-induced lung injury. Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or saline vehicle from postnatal days 1-14 while being continuously exposed to 5% CO(2) (Pa(CO(2)) elevated by 15-20 mmHg), 7% CO(2) (Pa(CO(2)) elevated by 35 mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%, CO(2), had significantly attenuated lung tissue macrophage influx and PHT, as evidenced by normalized pulmonary vascular resistance and right ventricular systolic function, decreased right ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. The level of CO(2) neither prevented increased tissue neutrophil influx nor led to improvements in decreased lung weight, septal thinning, impaired alveolarization, or decreased numbers of peripheral arteries. Bleomycin led to increased expression and content of lung tumor necrosis factor (TNF)-α, which was found to colocalize with tissue macrophages and to be attenuated by exposure to 7% CO(2). Inhibition of TNF-α signaling with the soluble TNF-2 receptor etanercept (0.4 mg/kg ip from days 1-14 on alternate days) prevented bleomycin-induced PHT without decreasing tissue macrophages and, similar to CO(2), had no effect on arrested alveolar development. Our findings are consistent with a preventive effect of therapeutic hypercapnia with 7% CO(2) on bleomycin-induced PHT via attenuation of macrophage-derived TNF-α. Neither tissue macrophages nor TNF-α appeared to contribute to arrested lung development induced by bleomycin. That 7% CO(2

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

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    Chun-Kuei Su


    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

  5. Treatment of alloxan and streptozotocin diabetes in rats by intrafamiliar homo (allo) transplantation of neonatal pancreases. (United States)

    Korec, R


    A total of 116 adult male and female rats of own inbred F3 up to 8th generation weighing 180-350 g was rendered diabetic by a single i. v. injection of either alloxan (40-50 mg kg-1) or streptozotocin (50-60 mg kg-1) and 1--2 weeks later subjected to the intrafamiliar homo(allo)transplantation of 2--5 minced, collagenase non digested pancreases either from own newborns or from newborns of sisters and brothers of the same family under the renal capsule. Out of the total, 24 animals (20.68%) were successfully cured. The cured rats examined with the aid of intravenous glucose tolerance test (IV) GTT monthly for one year showed fasting normonoglycemia with increased postglucose values and decreased KG being in the range of latent, borderline diabetes. In male rats IV GTT deteriorated in nine months without any transition into manifest diabetes or loss of body weight. Some animals cured by transplantation reached a normal survival time and were able to bring forth litters and suckle their newborns. In the rats with complete reversal of diabetes the transplants with well developed, vascularized islets, consisting predominantly of B-cells were found.

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

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    Didem Cemile Yesilirmak


    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.

  7. Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine. (United States)

    Poddar, Indrani; Callahan, Patrick M; Hernandez, Caterina M; Yang, Xiangkun; Bartlett, Michael G; Terry, Alvin V


    While impairments of cognition in schizophrenia have the greatest impact on long-term functional outcome, the currently prescribed treatments, antipsychotic drugs (APDs), do not effectively improve cognition. Moreover, while more than 20 years have been devoted to the development of new drugs to treat cognitive deficits in schizophrenia, none have been approved to date. One area that has not been given proper attention at the preclinical or clinical stage of drug development is the chronic medication history of the test subject. Hence, very little is known about how chronic treatment with drugs that affect multiple receptors like APDs influence the response to a potential pro-cognitive agent. Therefore, the purpose of this study was to evaluate the α7 nicotinic acetylcholine receptor (α 7 nAChR) partial agonist, tropisetron in rats chronically treated with APDs with distinct pharmacological profiles. Rats were treated orally with either risperidone (2.5 mg/kg/day) or quetiapine (25.0 mg/kg/day) for 30 or 90 days and then an acute injection of vehicle or tropisetron (3.0 mg/kg) was administered before training in a novel object recognition (NOR) task. After a 48 hr delay (when recollection of the familiar object was impaired in vehicle-treated animals) neither 30 nor 90 days of risperidone or quetiapine treatment improved NOR performance. In contrast, tropisetron markedly improved NOR performance in rats treated with either APD for 30 or 90 days. These animal data reinforce the argument that two commonly prescribed APDs are not pro-cognitive agents and that α 7 nAChR ligands like tropisetron have potential as adjunctive treatments in schizophrenia. Copyright © 2017. Published by Elsevier Inc.

  8. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

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    Dyuti Sharma


    Full Text Available Bronchopulmonary dysplasia (BPD is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3 during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14 were fed a control diet (n = 2, a PUFA ω-6 diet (n = 6, or a PUFA ω-3 diet (n = 6, starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female were exposed to hyperoxia (O2, n = 70 or to the ambient air (Air, n = 70. Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30, PUFA ω-6/air (n = 30, PUFA ω-3/O2 (n = 30, PUFA ω-3/air (n = 30, control/O2 (n = 10, and control/air (n = 10. After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20 and PUFA ω-6 groups (n = 60. Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30 compared to PUFA ω-6/O2 (n = 30 or to the control/O2 (n = 10, but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

  9. The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. (United States)

    Beheshti, Farimah; Hosseini, Mahmoud; Shafei, Mohammad Naser; Soukhtanloo, Mohammad; Ghasemi, Simagol; Vafaee, Farzaneh; Zarepoor, Leila


    and also Vit C significantly increased the time latency for entering the dark compartment in PA test. The serum thyroxine concentrations of the animals treated by all doses of the N. sativa extract as well as by Vit C were higher than that of the PTU group. Two hundred and four hundred milligrams/kilogram of NS extract and 100 mg/kg Vit C decreased the MDA concentration in hippocampal tissues, while increased thiol contents compared to the PTU group. The results of this study demonstrate that the hydroalcoholic extract of N. sativa have protective effects on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. The effects were comparable to Vit C and might be due to the protective effects of N. sativa extract against brain tissues' oxidative damage.

  10. Using bosentan to treat paraquat poisoning-induced acute lung injury in rats.

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    Zhongchen Zhang

    Full Text Available BACKGROUND: Paraquat poisoning is well known for causing multiple organ function failure (MODS and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning. OBJECTIVE: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat. METHOD: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning; the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day; and a control group (rats were administered intragastric physiological saline. On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1, endothelin-1 (ET-1, and hydroxyproline (HYP in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes. RESULT: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered. CONCLUSION: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

  11. Methylprednisolone protects cardiac pumping mechanics from deteriorating in lipopolysaccharide-treated rats

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    Ya-Hui eKo


    Full Text Available It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1 for 2 wk. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1 for 2 wk. Under conditions of anesthesia and open chest, we recorded left ventricular (LV pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax and the theoretical maximum flow (Qmax, using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV

  12. Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core. (United States)

    Cao, Jinyan; Dorris, David M; Meitzen, John


    Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised.

  13. 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.

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


    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

  14. Contribution of mineralocorticoid and glucocorticoid receptors to the chronotropic and hypertrophic actions of aldosterone in neonatal rat ventricular myocytes. (United States)

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


    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.

  15. Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro. (United States)

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


    Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. 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. 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. 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.

  16. Despite Differences in Cytosolic Calcium Regulation, Lidocaine Toxicity Is Similar in Adult and Neonatal Rat Dorsal Root Ganglia in Vitro (United States)

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


    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

  17. Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine

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    Ameneh Poorrostami


    Full Text Available Objective: Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each.  Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG (10 mg/kg daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ (40 mg/kg. Group 3: Epileptic group received normal saline (10 ml/kg. Group 4: Epileptic group was treated with LTG (10 mg/kg. Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg. Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg. At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy. Results: The mean values of TG, CHOL, AST, and ALT activity significantly rose (p

  18. Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model alters adult adipose tissue deposition and prevents hyperinsulinemia in male rats. (United States)

    Haley, Shannon; Neff, Kimberly; Gulliver, Kristina; Gough, Grace; Slater, Hillarie; Lane, Robert H; Moyer-Mileur, Laurie J


    Preterm infants are exposed to numerous stressors during hospitalization and by term corrected gestational age they have lower body weight but a greater proportion of total body as well as abdominal visceral adipose tissue (VAT) accumulation. Greater abdominal VAT stores have a known association with metabolic syndrome. Mechanical-tactile stimulation (MTS) improves modulation of stress response in both humans and rodents. We hypothesize that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in adult rats. Neonatal stress, administered to rat pups from postnatal days 5 to P9, consisted of needle puncture and hypoxic/hyperoxic challenge during 60 min of maternal separation (STRESS; n=20). Mechanical-tactile stimulation (MTS; n=20) was administered to rat pups for 10 min during maternal separation in the stress protocol. Control animals received standard care (CTL; n=20). MRI measured adult (P120) abdominal total fat mass, subcutaneous (SAT) and visceral adipose tissue (VAT). Body weight and fasting serum adiponectin, leptin, glucose, insulin, and corticosterone were also measured. STRESS results in elevated VAT/SAT ratio compared to CTL but lower abdominal total fat mass and abdominal SAT. STRESS males experience hyperinsulinemia. Both STRESS and MTS had elevated leptin with lower adiponectin and corticosterone compared to CTL. In summary, neonatal stress promotes greater abdominal VAT accumulation and, in males, caused hyperinsulinemia and hypoadiponectinemia. Importantly, MTS normalized the VAT/SAT ratio and prevented hyperinsulinemia. We speculate that MTS ameliorates some of the negative metabolic consequences of early life perturbations due to neonatal stress exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure

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    Lamartiniere Coral A


    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.

  20. Transcriptional effects of E3 ligase atrogin-1/MAFbx on apoptosis, hypertrophy and inflammation in neonatal rat cardiomyocytes.

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    Yong Zeng

    Full Text Available 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.

  1. Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress. (United States)

    Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe


    Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018. Published by Elsevier B.V.

  2. Efeitos de longo prazo do estresse neonatal com lipopolissacarídeo em ratos = Long-term effects of neonatal stress using lipopolysaccharide in rats

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    Lunardelli, Adroaldo


    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

  3. Immunohistochemical profile of some neurotransmitters and neurotrophins in the seminiferous tubules of rats treated by lonidamine

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    M Artico


    Full Text Available Lonidamine (LND or [1-(2,4-dichlorobenzyl-1H-indazole-3- carboxylic acid] is an anticancer and antispermatogenic drug that exerts a large number of effects on tumor cells and germ cells. Sexually mature male Sprague-Dawley rats were housed at 22°C on a 12-h light/12-h dark cycle 1 week before the experiments, with free access to food and water. LND was suspended in 0.5% methylcellulose at a concentration of 10 mg/mL and administered orally at the dose of 10 mL/kg (b.w. as a single dose. Control rats received an equal amount of vehicle. Testes were removed, fixed for 24 h in 2% glutaraldehyde and 2% paraformaldehyde in 0.1 M sodium phosphate (pH 7.2 at 22°C, rinsed with the same buffer, and stored at room temperature. From each sample, a block of tissue was removed by sectioning through the organ. After dehydration in ethanol at increasing concentrations (70-100%, each block was embedded in paraffin and serial 5 mm thick sections were cut using a rotatory microtome. The immunoreactivity for NTs has been observed in spermatogonia of untreated rats, while the rats treated with LND showed an immunohistochemical localization in all the stages of germinal cells. The generally well-expressed immunoreactivity for the neurotrophins receptors in treated rats observed in our study is presumably attributable to alterations of the receptors’ structure and/or expression leading to changes of the activity, affinity, localization or protein interactions that may depend on sensitization of ion channels (induced by LND. Neurotrophins (NTs appear to be interesting proteins for the modulation of sperm maturation and motility with a prominent role for the nerve growth factor (NGF, that may exert an autocrine or paracrine role.We therefore investigated the location and distribution of immunoreactivity for some neurotransmitters (SP, VIP, CGRP, nNOS, Chat, neurotrophins (NGF, BDNF, NT-3 and their own receptors (TrKA, TrKB, TrKC, p75 in the seminiferous tubules of

  4. Neuroprotection of VEGF-expression neural stem cells in neonatal cerebral palsy rats. (United States)

    Zheng, Xiang-Rong; Zhang, Shan-Shan; Yin, Fei; Tang, Jie-Lu; Yang, Yu-Jia; Wang, Xia; Zhong, Le


    Cerebral palsy (CP) is a very common neural system development disorder that can cause physical disability in human. Here, we studied the neuroprotective effect of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in newborn rats with cerebral palsy (CP). Seven-day-old Sprague-Dawley rats were randomly divided into four groups: sham operation (control group), PBS transplantation (PBS group), VEGF+NSCs transplantation (transgene NSCs group) and NSCs transplantation groups (NSCs group). PBS, Transgene NSCs and NSCs groups respectively received stereotactic injections of PBS, lentiviral vector (pGC-FU-VEGF) infected NSCs or a NSCs suspension in the left sensory-motor cortex 3 days after CP model was established. The NSCs activity, their impacts on neural cell growth and apoptosis, brain development and animal behaviors were examined on the animals up to age 35-days. As expected, unilateral carotid artery occlusion plus hypoxia (cerebral palsy model) resulted in severe neural developmental disorders, including slowed growth, increased in cortical neuron apoptosis, decreased cerebral cortex micro-vessel density and retarded behavior developments. Transplantation of NSCs not only resulted in increases in VEGF protein expression in rat brains, but also largely prevented the behavioral defects and brain tissue pathology that resulted from cerebral palsy procedure, with animals received VEGF transfected NSCs always being marginally better than these received un-transfected cells. In conclusion, NSCs transplantation can partially prevent/slow down the brain damages that are associated with CP in the newborn rats, suggesting a new possible strategy for CP treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes. (United States)

    Liu, Xue-Ru; Cao, Lu; Li, Tao; Chen, Lin-Lin; Yu, Yi-Yan; Huang, Wen-Jun; Liu, Li; Tan, Xiao-Qiu


    Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 μM (H2O2 group), propofol at 50 μM (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

  6. Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

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    Yi Pang


    Full Text Available Our previous study showed that a single lipopolysaccharide (LPS treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β levels, as well as reduced tyrosine hydroxylase (TH expression in the substantia nigra (SN of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg with or without IL-1ra (0.1 mg/kg, or sterile saline was injected intracerebrally into postnatal day 5 (P5 Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure.

  7. Posture effects on spontaneous limb movements, alternated stepping, and the leg extension response in neonatal rats (United States)

    Mendez-Gallardo, Valerie; Roberto, Megan E.; Kauer, Sierra D.; Brumley, Michele R.


    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. PMID:26655784

  8. Lactobacillus rhamnosus GG supernatant enhance neonatal resistance to systemic Escherichia coli K1 infection by accelerating development of intestinal defense. (United States)

    He, Xiaolong; Zeng, Qing; Puthiyakunnon, Santhosh; Zeng, Zhijie; Yang, Weijun; Qiu, Jiawen; Du, Lei; Boddu, Swapna; Wu, Tongwei; Cai, Danxian; Huang, Sheng-He; Cao, Hong


    The objective of this study was to determine whether Lactobacillus rhamnosus GG culture supernatant (LCS) has a preventive effect against gut-derived systemic neonatal Escherichia coli (E. coli) K1 infection. The preventive effects were evaluated in human colonic carcinoma cell line Caco-2 and neonatal rat models. Our in vitro results showed that LCS could block adhesion, invasion and translocation of E. coli K1 to Caco-2 monolayer via up-regulating mucin production and maintaining intestinal integrity. In vivo experiments revealed that pre-treatment with LCS significantly decrease susceptibility of neonatal rats to oral E. coli K1 infection as reflected by reduced bacterial intestinal colonization, translocation, dissemination and systemic infections. Further, we found that LCS treated neonatal rats have higher intestinal expressions of Ki67, MUC2, ZO-1, IgA, mucin and lower barrier permeability than those in untreated rats. These results indicated that LCS could enhance neonatal resistance to systemic E. coli K1 infection via promoting maturation of neonatal intestinal defense. In conclusions, our findings suggested that LCS has a prophylactic effect against systemic E. coli K1 infection in neonates. Future studies aimed at identifying the specific active ingredients in LCS will be helpful in developing effective pharmacological strategies for preventing neonatal E. coli K1 infection.

  9. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats. (United States)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole


    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  10. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats

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    Nasr A.M.N. El-Deen


    Full Text Available The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups.It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  11. Mediation of oxidative stress in hypothalamic ghrelin-associated appetite control in rats treated with phenylpropanolamine. (United States)

    Yu, C-H; Chu, S-C; Chen, P-N; Hsieh, Y-S; Kuo, D-Y


    Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  12. Neuroprotective effects of zinc on antioxidant defense system in lithium treated rat brain. (United States)

    Bhalla, Punita; Chadha, Vijayta Dani; Dhar, Rakesh; Dhawan, D K


    With a view to find out whether zinc affords protection against lithium toxicity the activities of antioxidant enzymes and lipid peroxidation profile were determined in the cerebrum and cerebellum of lithium treated female Sprague Dawley rats. Lipid peroxidation was significantly increased in both the cerebrum and the cerebellum of animals administered with lithium for a total duration of 4 months as compared to the normal control group. On the contrary, the activities of catalase and glutathione-s-transferase (GST) were significantly reduced after 4 months of lithium treatment. The activity of superoxide dismutase (SOD) was significantly increased in the cerebrum after 4 months lithium administration, whereas in the cerebellum the enzyme activity was unaffected. No significant change in the levels of reduced glutathione (GSH) was found in either cerebrum or cerebellum after 2 months of lithium treatment. However, 4 months lithium treatment did produce significant changes in GSH levels in the cerebrum and in the cerebellum. Zinc supplementation for 4 months in lithium-treated rats significantly increased the activities of catalase and GST in the cerebellum, showing that the treatment with zinc reversed the lithium induced depression in these enzyme activities. Though, zinc treatment tended to normalize the SOD activity in the cerebrum yet it was still significantly higher in comparison to normal levels. From the present study, it can be concluded that the antiperoxidative property of zinc is effective in reversing the oxidative stress induced by lithium toxicity in the rat brain.

  13. Neonatal tactile stimulation decreases depression-like and anxiety-like behaviors and potentiates sertraline action in young rats. (United States)

    Freitas, Daniele; Antoniazzi, Caren T D; Segat, Hecson J; Metz, Vinícia Garzella; Vey, Luciana Taschetto; Barcelos, Raquel C S; Duarte, Thiago; Duarte, Marta M M F; Burger, Marilise Escobar


    It is well known that events which occur in early life exert a significant influence on brain development, what can be reflected throughout adulthood. This study was carried out in order to assess the influence of neonatal tactile stimulation (TS) on behavioral and morphological responses related to depression-like and anxiety-like behaviors, assessed following the administration of sertraline (SERT), a selective serotonin re-uptake inhibitor (SSRI). Male pups were submitted to daily TS, from postnatal day 8 (PND8) to postnatal day 14 (PND14), for 10 min every day. On PND50, adult animals were submitted to forced swimming training (15 min). On PND51, half of each experimental group (UH and TS) received a single sub-therapeutic dose of sertraline (SER, 0.3mg/kg body weight, i.p.) or its vehicle (C, control group). Thirty minutes after injection, depression-like behaviors were quantified in forced swimming test (FST, for 5 min). On the following day, anxiety-like behaviors were assessed in elevated plus maze (EPM), followed by biochemical assessments. TS per se increased swimming time, decreasing immobility time in FST. Besides, TS per se was able to increase frequency of head dipping and time spent in the open arms of EPM, resulting in decreased anxiety index. In addition, groups exposed to TS showed decreased plasma levels of corticosterone per se. Interestingly, while TS exposure significantly potentiated the antidepressant activity of a subtherapeutic dose of SERT, this drug was able to exacerbate TS-induced anxiolytic activity, as observed in FST and EPM, respectively. Decreased plasma levels of both corticosterone and cortisol in animals exposed to TS and treated with SERT are able to confirm the interesting interaction between this neonatal handling and the antidepressant drug. From our results, we conclude that neonatal TS is able to exert beneficial influence on the ability to cope with stressful situations in adulthood, preventing depression and favorably

  14. Distribution of glutathione peroxidase 1 in liver tissues of healthy and diabetic rats treated with capsaisin. (United States)

    Deprem, T; Yıldız, S E; Sari, E K; Bingol, S A; Tasci, S K; Aslan, S; Sozmen, M; Nur, G


    We investigated the immunohistochemical localization of glutathione peroxidase 1 (GPx 1) and the structural changes that occur in the livers of healthy and diabetic rats that were treated with capsaisin (CAP). Fifty female rats were divided into five groups: group 1, sham; group 2, untreated control; group 3, CAP-treated; group 4, streptozotocin (STZ) diabetic; group 5, STZ diabetic + CAP-treated. STZ was administered to groups 4 and 5; after verifying diabetes, CAP was administered daily for 2 weeks to groups 3 and 5. Diffuse, microvesicular and some macrovesicular fatty degeneration were observed in the cytoplasms of hepatocytes in the livers of the diabetic group. In the CAP-treated diabetic group, fat degeneration in the livers decreased slightly by day 7. Irregularity of the external contours of nuclei of the hepatocytes, swelling of the nuclei, and slight anisocytosis and anisokaryosis were observed in the hepatocytes of the diabetic group. In the CAP-treated diabetic groups, the severity of anisocytosis and anisokaryosis decreased slightly by day 7. In all groups, GPx 1 showed similar immunolocalization, but in the diabetic and diabetic + CAP groups, GPx 1 immunoreactivity was less than in the other groups. GPx 1 immunoreactivity in the CAP-treated diabetic group was weaker than in the diabetic group. In all groups, GPx 1 immunoreactivity was diffusely cytoplasmic in some of the hepatocytes, and diffusely cytoplasmic and diffusely nuclear in other hepatocytes. Also, GPx 1 immunoreactivity in the liver was more intense in the hepatocytes around Kiernan's space. We found that CAP caused a decrease in GPx 1.

  15. Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

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    Dongsun Park


    Full Text Available Objective. Since oligodendrocyte progenitor cells (OPCs are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE, the present study was aimed at investigating the protective effects of N-acetyl-L-cysteine (NAC, a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

  16. Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats (United States)

    Jaeckle Santos, Lane J.; Li, Changhong; Doulias, Paschalis-Thomas; Ischiropoulos, Harry; Worthen, G. Scott; Simmons, Rebecca A.


    Intrauterine growth restriction (IUGR) leads to development of type 2 diabetes (T2D) in adulthood. The mechanisms underlying this phenomenon have not been fully elucidated. Inflammation is associated with T2D; however, it is unknown whether inflammation is causal or secondary to the altered metabolic state. Here we show that the mechanism by which IUGR leads to the development of T2D in adulthood is via transient recruitment of T-helper 2 (Th) lymphocytes and macrophages in fetal islets resulting in localized inflammation. Although this immune response is short-lived, it results in a permanent reduction in islet vascularity and impaired insulin secretion. Neutralizing interleukin-4 antibody therapy given only in the newborn period ameliorates inflammation and restores vascularity and β-cell function into adulthood, demonstrating a novel role for Th2 immune responses in the induction and progression of T2D. In the neonatal stage, inflammation and vascular changes are reversible and may define an important developmental window for therapeutic intervention to prevent adult-onset diabetes. PMID:24408314

  17. Mere odor exposure learning in the rat neonate immediately after birth and 1 day later. (United States)

    Miller, Stacie S; Spear, Norman E


    Rat pups are more resistant to retroactive associative interference 3 hr after birth than 24 hr later [Cheslock et al. [2004] Developmental Science, 7, 581-598]. 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 1 day later and tested after a given retention interval (3 or 27 hr [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 4-min activity test including a 2-min baseline period and 2 min of odor exposure. Overall activity was scored during tape-playback. Odor-exposed pups were more active than nonexposed 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 1 day apart, newborn rats just hours old lack many of the experiences that a 1-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.

  18. Effects of air ions on the neonatal growth of laboratory rats (United States)

    Hinsull, S. M.; Bellamy, D.; Head, E. L.


    The effect of continuous positive and negative ionization on the growth of rats during the pre and post natal period, up to 10 weeks of age was investigated. It was found that continuous exposure to 1.0×104 pos. ions/ml had no detrimental effect on the animals at any stage of their development. In contrast, exposure to 1.0×104 neg. ions/ml, during gestation and the early post natal period, resulted in some adverse effects on growth and development. However, when exposure to this level of negative ions began at the time of weaning, no adverse effects were observed.

  19. 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


    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.

  20. Comparison of hemihypoglossal- and accessory-facial neurorrhaphy for treating facial paralysis in rats. (United States)

    Li, Dezhi; Wan, Hong; Feng, Jie; Wang, Shiwei; Su, Diya; Hao, Shuyu; Schumacher, Michael; Liu, Song


    The aim of this study was to determine the effectiveness of hypoglossal-facial nerve "side"-to-end (HemiHN-FN) and accessory-facial nerve end-to-end (AN-FN) neurorrhaphy using a predegenerated nerve graft (PNG) for reanimating facial paralysis in a rat FN injury model. A total of 25 rats with complete unilateral facial paralysis resulting from section of the right FN were divided into 5 groups (n=5 each) that were submitted to immediate, delayed (3 months after FN injury) or no (control) FN reconstruction procedures involving HemiHN-FN or AN-FN neurorrhaphy. Approximately 3 months after FN reconstruction, cholera toxin subunit B conjugate Alexa 555 (CTB-Alexa 555) was injected into the ipsilateral whisker pad muscle and CTB-Alexa 555-labeled neurons were observed in the hypoglossal or accessory nuclei of all the FN reconstruction rats, but none of these neurons were found in the controls. There were numerous myelinated and nonmyelinated axons in both PNG and repaired FN of the FN reconstruction rats. No differences were found for these numbers between the two neurorrhaphy methods for each of the treatment time points, indicating the equal effectiveness of axon regeneration. However, a significantly higher number of CTB-Alexa 555-labeled neurons was observed in the hypoglossal nucleus of the immediate HemiHN-FN neurorrhaphy-treated rats when compared to that in the accessory nucleus of the immediate AN-FN neurorrhaphy-treated rats, consistent with the surface values of the recorded MAPs at the whisker pad muscle while electro-stimulating the FN. These results suggest that HemiHN-FN neurorrhaphy produces more efficient innervation of the paralyzed facial muscles than AN-FN neurorrhaphy without sacrificing ipsilateral hypoglossal function. Taking into consideration the clinical relevance of these findings for postoperative complications and functional reanimation in relation to the central plasticity, we suggest that HemiHN-FN neurorrhaphy may be the preferable facial

  1. Memory and hippocampal architecture following short-term midazolam in western diet-treated rats. (United States)

    Rosenberger, Dorothea S; Falangola, Maria F; Ledreux, Aurélie; Nie, Xingju; Suhre, Wendy M; Boger, Heather A; Granholm, Ann-Charlotte


    The impact of short-term benzodiazepine exposure on cognition in middle-aged or older patients is a highly debated topic among anesthesiologists, critical care physicians and public media. "Western diet" (WD) consumption is linked to impaired cognition as well. The combination of benzodiazepines with substantial exposure to WD might set the stage for increased hippocampal vulnerability for benzodiazepines leading to exaggerated cognitive impairment in the postoperative period. In this study, Fischer 344 rats were fed either WD or standard rodent diet from 5 to 10.5 months of age. Rats were exposed to midazolam or placebo two days prior to an MRI scan using Diffusional Kurtosis Imaging (DKI) to assess brain microstructural integrity, followed by behavioral testing using a water radial arm maze. Hippocampal tissue was collected to assess alterations in protein biochemistry in brain regions associated with learning and memory. Our results showed that rats exposed to the combination of midazolam and WD had significantly delayed time of learning and exhibited spatial memory impairment. Further, we observed an overall increase of kurtosis metrics in the hippocampus and increased expression of the mitochondrial protein VDAC2 in midazolam-treated rats. Our data suggest that both the short-acting benzodiazepine midazolam and WD contribute to negatively affect the brain in middle-aged rats. This study is the first application of DKI on the effects of midazolam and WD exposure, and the findings demonstrate that diffusion metrics are sensitive indicators of changes in the complexity of neurite architecture. Published by Elsevier Ireland Ltd.

  2. Neuronal reorganization in adult rats neonatally exposed to (±-3,4-methylenedioxymethamphetamine

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    Michael T. Williams


    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.

  3. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

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    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare


    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  4. [Protective effects of AST and ASI on memory impairment and its mechanism in senescent rats treated by GC]. (United States)

    Li, Weizu; Li, Weiping; Yin, Yanyan; Gong, Huiling; Wu, Guocui; Zhu, Fenfang


    To study the protective effects and mechanisms of astragaloside (AST) and astragalus saponin I (ASI) on the memory impairment in senescent rats treated by glucocorticoid (GC). Y maze test was performed to determine the effects of AST and ASI on memory impairment of hydrocortisone(HC)-induced senescent rats. Using Ca2+ sensitive fluorescent indicator (Furo-2), free intracellular calcium concentration ([Ca2+]i) was measured by double wavelength fluorescence sepectrophotometer in thymocytes and hippocampal neurons induced dexamethasone (DEX). And apoptosis was detected by DNA gel electrophoresis and flow cytometry. Compared with HC control, AST and ASI can improve the memory of the senescent rats treated by HC, lower [Ca2+]i and suppress apoptosis of thymocytes and hippocampal neurons induced by DEX. AST and ASI can delay the aging in rats treated by HC, and its mechanism may includ lowering[Ca2+]i and suppressing the apoptosis of thymocytes and hippocampal neurons.

  5. Neonatal Venous Thromboembolism

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    Kristina M. Haley


    Full Text Available Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE, and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults. Platelet function, pro- and anticoagulant proteins concentrations, and fibrinolytic pathway protein concentrations are developmentally regulated and generate a hemostatic homeostasis that is unique to the neonatal time period. The clinical picture of a critically ill neonate combined with the physiologically distinct neonatal hemostatic system easily fulfills the criteria for Virchow’s triad with venous stasis, hypercoagulability, and endothelial injury and puts the neonatal patient at risk for VTE development. The presentation of a VTE in a neonate is similar to that of older children or adults and is dependent upon location of the VTE. Ultrasound is the most common diagnostic tool employed in identifying neonatal VTE, but relatively small vessels of the neonate as well as frequent low pulse pressure can make ultrasound less reliable. The diagnosis of a thrombophilic disorder in the neonatal population is unlikely to change management or outcome, and the role of thrombophilia testing in this population requires further study. Treatment of neonatal VTE is aimed at reducing VTE-associated morbidity and mortality. Recommendations for treating, though, cannot be extrapolated from guidelines for older children or adults. Neonates are at risk for bleeding complications, particularly younger neonates with more fragile intracranial vessels. Developmental alterations in the

  6. Transport of ascorbic acid and dehydroascorbic acid by pancreatic islet cells from neonatal rats

    DEFF Research Database (Denmark)

    Zhou, A; Farver, O; Thorn, N A


    .14.17.3). The enzyme needs ascorbic acid for activity as well as copper and molecular oxygen. The present work shows that pancreatic islet cells prepared from overnight cultures of isolated islets from 5-7-day-old rats accumulate 14C-labelled ascorbic acid by a Na(+)-dependent active transport mechanism which involves....... Dehydroascorbic acid was converted to ascorbic acid by an unknown mechanism after uptake. The uptake of both ascorbic acid and dehydroascorbic acid was inhibited by tri-iodothyronine, and uptake of ascorbic acid, but not of dehydroascorbic acid, was inhibited by glucocorticoids. Isolated secretory granules...... a saturable process (estimated Km 17.6 microM). Transport was inhibited by ouabain, phloridzin, cytochalasin B, amiloride and probenecid. Glucose inhibited or stimulated uptake, depending on the length of incubation time of the cells. The uptake of dehydroascorbic acid was linearly dependent on concentration...

  7. Air-stepping in neonatal rats: A comparison of L-dopa injection and olfactory stimulation. (United States)

    Jamon, M; Maloum, I; Riviere, G; Bruguerolle, B


    The kinematic parameters of air-stepping induced by 2 methods known to elicit locomotion (olfactory stimulation vs. L-dopa injection) were compared in 3-day-old rats. In the 1st stage, suspended pups were induced to step with an olfactory stimulus of soiled shavings from the nest. In the 2nd stage, they received a subcutaneous injection of L-dopa. Their movements were faster, with a larger amplitude and a phase delay in ipsilateral coupling. Third, the olfactory stimulus was presented in conjunction with L-dopa. The characteristics of locomotion returned to the same level as with the olfactory stimulus alone. These results suggest that olfactory stimulation involves higher nerve centers able to modulate the dopaminergic pathways. They are discussed in relation to the neural structure involved in locomotion.

  8. Hydrogen peroxide-mediated interference competition by Streptococcus pneumoniae has no significant effect on Staphylococcus aureus nasal colonization of neonatal rats. (United States)

    Margolis, Elisa


    It has been proposed that the relative scarcity of Staphylococcus aureus and Streptococcus pneumoniae cocolonization in the nasopharynxes of humans can be attributed to hydrogen peroxide-mediated interference competition. Previously it has been shown in vitro that H(2)O(2) produced by S. pneumoniae is bactericidal to S. aureus. To ascertain whether H(2)O(2) has this inhibitory effect in the nasal passages of neonatal rats, colonization experiments were performed with S. aureus and S. pneumoniae. The results of these experiments with neonatal rats are inconsistent with the hypothesis that hydrogen peroxide-mediated killing of S. aureus by S. pneumoniae is responsible for the relative scarcity of cocolonization by these bacteria. In mixed-inoculum colonization experiments and experiments where S. aureus invaded the nasopharynxes of rats with established S. pneumoniae populations, the density of S. aureus did not differ whether the S. pneumoniae strain was H(2)O(2) secreting or non-H(2)O(2) secreting (SpxB). Moreover, the advantage of catalase production by S. aureus in competition with a non-catalase-producing strain (KatA) during nasal colonization was no greater in the presence of H(2)O(2)-producing S. pneumoniae than in the presence of non-H(2)O(2)-producing S. pneumoniae.

  9. Cerebral Area Differential Redox Response of Neonatal Rats to Selenite-Induced Oxidative Stress and to Concurrent Administration of Highbush Blueberry Leaf Polyphenols. (United States)

    Ferlemi, Anastasia-Varvara; Mermigki, Penelope G; Makri, Olga E; Anagnostopoulos, Dimitrios; Koulakiotis, Nikolaos S; Margarity, Marigoula; Tsarbopoulos, Anthony; Georgakopoulos, Constantinos D; Lamari, Fotini N


    Our goal was to delineate the mechanisms of selenite-induced oxidative stress in neonatal rats and investigate the potential of blueberry leaf polyphenols to counteract the induced stress. Vaccinium corymbosum leaf decoction (BLD) was analyzed by UPLC-MS and LC-DAD, along with its in vitro antioxidant activity (DPPH radical scavenging, FRAP, ferrous chelation). Newborn suckling Wistar rats were randomly divided into three groups: 'Se' and 'SeBLD' received 20 μmol Na2SeO3/kg BW subcutaneously (PN day 10); 'SeBLD' received 100 mg dry BLD/kg BW intraperitoneally (PN11 and 12) and Group 'C' received normal saline. Βiochemical analysis revealed tissue-specific effects of selenite. Brain as a whole was more resistant to selenite toxicity in comparison to liver; midbrain and cerebellum were in general not affected, but cortex was moderately disturbed. Liver lipid peroxidation, GSH, SOD, CAT, GPx were significantly affected, whereas proteolytic activity was not. BLD, which is rich in chlorogenic acid and flavonols (especially quercetin derivatives), exerted significant antioxidant protective effects in all regions. In conclusion, we provide for the first time an insight to the neonatal rat cerebral and liver redox response against a toxic selenite dose and blueberry leaf polyphenols.

  10. Prolactin released in vitro from the pituitary of lactating, pregnant, and steroid-treated female or male rats stimulates prolactin secretion from pituitary lactotropes of male rats. (United States)

    Mena, Flavio; Navarro, Nilda; Castilla, Alejandra; Morales, Teresa; Fiordelisio, Tatiana; Cárabez, Alfonso; Aguilar, Manuel B; Huerta-Ocampo, Icnelia


    We have previously shown that soluble factor(s) in conditioned media (CM) from the central and peripheral regions of the anterior pituitary (AP) gland of lactating rats promoted the in vitro dose-related release of prolactin (PRL) from pituitary glands of male rats. In the present experiments we sought to determine whether CM from rats in different physiological states provoked similar effects (like those of lactating rats), and the nature of the factors, whether 23K PRL or other variants of the hormone, were responsible for these effects. Stimulatory effects were induced by CM from pregnant females and steroid-treated castrated males or females, but not from untreated castrated rats, intact males, or by a PRL standard. More potent effects occurred with CM from APs of early- than from mid- or late-lactating rats, and from rats unsuckled for 8 or 16 h than from those unsuckled for 32 h. With respect to the nature of factor(s) responsible for these effects, immunoprecipitation of PRL from the CM of lactating females and of steroid-treated, castrated males eliminated, whereas dephosphorylation or deglycosylation of CM of lactating rats greatly increased its effects upon PRL release. Also, electrophoretic analysis and Western blotting of the CM proteins under native and denaturing conditions revealed a variety of PRL variants, ranging from 14 to <90 kDa, in CM from lactating rats, and the main effects on PRL release were provoked by the 23- to 46-kDa PRL variants. These results indicate that specific effects upon male rat lactotropes may be exerted by PRL variants released from APs of lactating and non-lactating rats. Copyright 2009 S. Karger AG, Basel.

  11. Developmental toxic effects in suckling pups of rats from dams treated with betamethasone

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    M. K. Shindala


    Full Text Available Suckling pups of rats from dams treated with betamethasone 0.3, 0.6, 1.2 mg/kg, i.p. given once daily for 10 consecutive days (first nursing period demonstrated in a dose – dependent manner significant decreased (P<0.05 the percentage of survival of the pups to weaning, body weight, index of development, whereas brain, heart, kindey, lung,liver / body weight ratio significantly increased (P<0.05 as well as delays in physical maturation (ear opening, fur development, tooth eruption, eye opening in the pups. Swimming scores on postnatal day 9, 13, 15, 17, 20 was significantly decreased (P<0.05 in offspring from mothers treated with betamethasone 1.2 mg/kg, i.p. In conclusion, the results suggest that betamethasone induced developmental toxic effects in suckling pups exposed to its through the milk.

  12. Study on acute ulcerous pain in rats treated with aqueous root extract of Lonchocarpus cyanescens

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    Adegbolagun Temitope Adeoye


    Full Text Available Objective: To evaluate the antiulcer and analgesic effects of the aqueous root extract of Lonchocarpus cyanescens (L. cyanescens since the plant is said to have medicinal properties. Methods: The filtrate of the aqueous root extract of the plant (100 mg/mL was used to evaluate for antiulcer activity in 20 rats divided into five groups of four rats each, which were Groups A, B, and C that received 100, 200 and 300 mg/kg doses respectively, while Group D was served as negative control and animals of Group E received 20 mg/kg dose of ranitidine. Indomethacin at a dose of 15 mg/kg was used to induce ulcer on the day of sacrifice. For acetic writhing test (antinociception, same design was used except that Group E received 100 mg/kg dose of acetyl salicylic acid as standard drug. Abdominal contractions were induced in the animals by intraperitoneal administration of 10 mL/kg of 0.6% of acetic acid. Results: The aqueous root extract of L. cyanescens at all doses (100, 200 and 300 mg/ kg showed significant (P < 0.05 decrease in ulcer parameters compared with the negative control. The extract also produced a significant (P < 0.05 decrease in the number of writhing reflexes in treated rats compared with negative control. Conclusions: The aqueous root extract of L. cyanescens exhibited both antiulcer and analgesic effects justifying folklore claim for the health benefits of this plant.

  13. Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation. (United States)

    Cai, Xiaxia; Bao, Lei; Wang, Nan; Xu, Meihong; Mao, Ruixue; Li, Yong


    Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water), alcohol control group (basal diet, 50% alcohol (v/v)), dextrose control group (basal diet, isocaloric amount of dextrose), and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg(-1) respectively, 50% alcohol (v/v)). The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to identify liver metabolite profiles. Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid), as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine) in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, L-leucine, alanyl-leucine and L-phenylalanine. These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

  14. Ontogeny of gender-specific responsiveness to stress and glucocorticoids in the rat and its determination by the neonatal gonadal steroid environment. (United States)

    Patchev, V K; Hayashi, S; Orikasa, C; Almeida, O F


    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

  15. Single variant bottleneck in the early dynamics of H. influenzae bacteremia in neonatal rats questions the theory of independent action (United States)

    Shao, Xinxian; Levin, Bruce; Nemenman, Ilya


    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.

  16. Postsynaptic GABA(B Receptors Contribute to the Termination of Giant Depolarizing Potentials in CA3 Neonatal Rat Hippocampus

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    Ilgam Khalilov


    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.

  17. The synthetic progestin, gestodene, affects functional biomarkers in neonatal rat osteoblasts through an estrogen receptor-related mechanism of action. (United States)

    Enríquez, Juana; García, Gustavo; Herrero, Bertha; Larrea, Fernando


    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.

  18. Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats

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    Taizhe eQian


    Full Text Available In the developing cerebral cortex, the marginal zone (MZ, consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl−]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na+, K+-2Cl− cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na+ channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of

  19. Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats.

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    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

  20. Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI. (United States)

    Waddell, Jaylyn; Hanscom, Marie; Shalon Edwards, N; McKenna, Mary C; McCarthy, Margaret M


    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.

  1. 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

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    Cristobal eRío-Alamos


    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.

  2. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

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    Amanda L. Smith


    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

  3. G-CSF ameliorates neuronal apoptosis through GSK-3β inhibition in neonatal hypoxia–ischemia in rats (United States)

    Li, Li; Klebe, Damon; Doycheva, Desislava; McBride, Devin W.; Krafft, Paul R.; Flores, Jerry; Zhou, Changman; Zhang, John H.; Tang, Jiping


    Granulocyte-colony stimulating factor (G-CSF), a growth factor, has known neuroprotective effects in a variety of experimental brain injury models. Herein we show that G-CSF administration attenuates neuronal apoptosis after neonatal hypoxia-ischemia (HI) via glycogen synthase kinase-3β (GSK-3β) inhibition. Ten day old Sprague-Dawley rat pups (n=157) were subjected to unilateral carotid artery ligation followed by 2.5hrs of hypoxia or sham surgery. HI animals received control siRNA, GSK-3β siRNA (4μL/pup), G-CSF (50μg/kg), G-CSF combined with 0.1 or 0.4nM G-CSF receptor (G-CSFR) siRNA, phosphatidylinositol 3-kinase (PI3K) inhibitor Wortmannin (86ng/pup), or DMSO (vehicle for Wortmannin). Pups were euthanized 48hrs post-HI to quantify brain infarct volume. G-CSFR, activated Akt (p-Akt), activated GSK-3β (p-GSK-3β), Cleaved Caspase-3 (CC3), Bcl-2, and Bax were quantified using Western blot analysis and the localizations of each was visualized via immunofluorescence staining. Neuronal cell death was determined using terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL). Our results showed p-GSK-3β increased after HI until its peak at 48hrs post-ictus, and both GSK-3β siRNA and G-CSF administration reduced p-GSK-3β expression, as well as infarct volume. p-GSK-3β and CC3 were generally co-localized in neurons. Furthermore, G-CSF increased p-Akt expression and the Bcl-2/Bax ratio and also decreased p-GSK-3β and CC3 expression levels in the ipsilateral hemisphere, which were all reversed by G-CSFR siRNA, Wortmannin, and GSK-3β siRNA. In conclusion, G-CSF attenuated caspase activation and reduced brain injury by inhibiting GSK-3β activity after experimental HI in rat pups. This neuroprotective effect was abolished by both G-CSFR siRNA and Wortmannin. PMID:25448005

  4. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

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    Sopi Ramadan B


    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

  5. Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats. (United States)

    Katsuragi, Shinji; Ikeda, Tomoaki; Date, Isao; Shingo, Tetsuro; Yasuhara, Takao; Mishima, Kenichi; Aoo, Naoya; Harada, Kazuhiko; Egashira, Nobuaki; Iwasaki, Katsunori; Fujiwara, Michihiro; Ikenoue, Tsuyomu


    Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average

  6. Insular neural system controls decision-making in healthy and methamphetamine-treated rats (United States)

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi


    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

  7. Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

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    da-Silva C.A.


    Full Text Available Erythrocytes may play a role in glucose homeostasis during the postprandial period. Erythrocytes from diabetic patients are defective in glucose transport and metabolism, functions that may affect glycogen storage. Phenobarbital, a hepatic enzyme inducer, has been used in the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM, increasing the insulin-mediated glucose disposal. We studied the effects of phenobarbital treatment in vivo on glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl in femoral and suprahepatic veins the erythrocyte glycogen content was 45.4 ± 1.1 and 39.1 ± 0.8 µg/g Hb (mean ± SEM, N = 4-6 in the femoral artery and vein, respectively, and 37.9 ± 1.1 in the portal vein and 47.5 ± 0.9 in the suprahepatic vein. Diabetic rats (blood glucose, 300-350 mg/dl presented low (P<0.05 erythrocyte glycogen content, i.e., 9.6 ± 0.1 and 7.1 ± 0.7 µg/g Hb in the femoral artery and vein, respectively, and 10.0 ± 0.7 and 10.7 ± 0.5 in the portal and suprahepatic veins, respectively. After 10 days of treatment, phenobarbital (0.5 mg/ml in the drinking water did not change blood glucose or erythrocyte glycogen content in control rats. In diabetic rats, however, it lowered (P<0.05 blood glucose in the femoral artery (from 305 ± 18 to 204 ± 45 mg/dl and femoral vein (from 300 ± 11 to 174 ± 48 mg/dl and suprahepatic vein (from 350 ± 10 to 174 ± 42 mg/dl, but the reduction was not sufficient for complete recovery. Phenobarbital also stimulated the glycogen synthesis, leading to a partial recovery of glycogen stores in erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 ± 3.8 µg/g Hb in the femoral artery and 30.9 ± 0.9 µg/g Hb in the suprahepatic vein (P<0.05. These data indicate that phenobarbital activated some of the insulin-stimulated glucose metabolism steps which were

  8. Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia?

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    Badreldin H Ali

    Full Text Available Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD. Similar benefits have also been ascribed to the dietary supplement gum acacia (GA. Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE on adenine-induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w to induce CKD, GA in the drinking water (15% w/v, or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments, during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation.

  9. Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats. (United States)

    Malhotra, Anshoo; Dhawan, Devinder K


    The present study was designed to evaluate the protective role of zinc in attenuating the adverse effects induced by lithium in blood of female Wistar rats. Female Wistar rats received lithium in the form of lithium carbonate in diet at a dose level of 1.1 g/kg diet, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L drinking water, or lithium plus zinc treatments in the combined group for a total duration of 2 months. Effects of the treatments were studied on antioxidant defense system, various hematologic parameters, and percentage of (65)Zn-specific activity. Lithium treatment resulted in a significant increase in lipid peroxidation levels but caused a significant decrease in reduced glutathione levels and the activities of catalase, glutathione S-transferase, and superoxide dismutase. Lithium treatment also caused a significant decrease in the activities of aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase. However, it resulted in a significant increase in total leukocyte counts, neutrophils, and lymphocyte counts as well as zinc protoporphyrin levels, whereas a significant decrease in counts of monocytes, eosinophils, and percentage specific activity of (65)Zn in blood and its various fractions was noticed. Furthermore, lithium treatment caused a significant decrease in serum zinc levels. However, zinc supplementation to lithium-treated rats effectively raised the reduced glutathione levels and also normalized lipid peroxidation and the activities of antioxidative enzymes, which included catalase, glutathione S-transferase, and superoxide dismutase. Moreover, zinc supplementation could raise the activities of the enzymes aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase as well as the percentage uptake values of (65)Zn in blood and its fractions. The study suggests that zinc, as a nutritional supplement, has the potential in attenuating most of the adverse effects induced by lithium

  10. Tissue dyslipidemia in salmonella-infected rats treated with amoxillin and pefloxacin

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    Rotimi Solomon O


    Full Text Available Abstract Background This study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin. Methods Animals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly and the remaining three groups with pefloxacin (5.71mg/kg body weight, 12 hourly for 5 and 10 days respectively. Uninfected control animals received 0.1ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated. Results Salmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL, erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p Conclusion The findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis.

  11. Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with α-Naphthylisothiocyanate (United States)

    Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro


    We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with α-naphthylisothiocyanate (ANIT) in comparison with that of vitamin E (VE). Rats orally received Brazilian propolis ethanol extract (BPEE) (25, 50, or 100 mg/kg), VE (250 mg/kg) or vehicle at 12 h after intraperitoneal injection of ANIT (75 mg/kg) and were killed 24 h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50 mg/kg) administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100 mg/kg) was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE. PMID:23710219

  12. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4 Treated Rats

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    Mohammed Riaz Hasan Chowdhury


    Full Text Available Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (−-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4 treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA, nitric oxide, advanced protein oxidation products level (APOP, and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  13. Antisense in vivo knockdown of synaptotagmin I by HVJ-liposome mediated gene transfer attenuates ischemic brain damage in neonatal rats. (United States)

    Omae, Tadaki; Yoshioka, Hiroshi; Tanaka, Taro; Nagai, Hideyuki; Saji, Makoto; Noda, Kazuko; Kobayashi, Shizuka; Sugimoto, Tohru


    Synaptic release of the excitatory amino acid glutamate is considered as an important mechanism in the pathogenesis of ischemic brain damage in neonates. Synaptotagmin I is one of exocytosis-related proteins at nerve terminals and considered to accelerate the exocytosis of synaptic vesicles by promoting fusion between the vesicles and plasma membrane. To test the possibility that antisense in vivo knockdown of synaptotagmin I modulates the exocytotic release of glutamate, thus suppressing the excitotoxic intracellular processes leading to neuronal death following ischemia in the neonatal brain, we injected antisense oligodeoxynucleotides (ODNs) targeting synaptotagmin I (0.3 (AS), 0.15 (0.5 AS), or 0.03 microg (0.1 AS), or vehicle) into the lateral ventricles of 7-day-old rats by using a hemagglutinating virus of Japan (HVJ)-liposome mediated gene transfer technique. At 10 days of age, these rats were subjected to an electrical coagulation of the right external and internal carotid arteries, then the insertion of a solid nylon thread into the right common carotid artery toward the ascending aorta up to 10-12 mm from the upper edge of the sternocleidomastoid muscle. Cerebral ischemia was induced by clamping the left external and internal carotid arteries with a clip, and ended by removing the clip 2h later. Twenty-four hours after the end of ischemia, the extent of ischemic brain damage was neuropathologically and quantitatively evaluated in the neocortex and striatum. While the relative volume of damage in the cerebral cortex and striatum of the vehicle group was extended to 40% and 13.7%, respectively, that in the AS group was significantly reduced to 4.8% and 0.6%. In the 0.5 AS group, the relative volume of ischemic damage in the cerebral cortex and striatum was reduced to 20.5% and 15.4%, respectively, and the difference between the 0.5 AS group and vehicle group was statistically significant in the neocortex, but not in the striatum. These results indicated

  14. Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt. (United States)

    Thomas, Jennifer D; Sather, Tamie Miura; Whinery, Lynn A


    Children exposed to alcohol prenatally may suffer from severe brain damage, expressed as a variety of behavioral problems, including hyperactivity and learning deficits. There is a critical need to identify effective treatments for fetal alcohol effects. Physical exercise enhances cognitive ability and increases neurogenesis in the hippocampus, a brain area important for learning and memory. Thus, the present study examined whether physical exercise might reduce the severity of alcohol-induced behavioral alterations. Sprague-Dawley rats were intubated with 5.25 g/kg/day ethanol during the third trimester equivalent (postnatal days [PDs] 4-9). Intubated sham control and nontreated controls were included. From PD 21 to PD 51, half of the subjects were given access to running wheels. On PD 52, subjects were tested on the Morris water maze, and on PD 60, open field activity levels were measured. Morris maze performance was significantly impaired among ethanol-exposed subjects; exercise significantly improved performance of all groups. Similarly, ethanol-exposed subjects were overactive in the open field, an effect attenuated with exercise. In sum, these data suggest that exercise may increase neuronal plasticity not only in controls, but also in subjects exposed to alcohol during development.

  15. Dabigatran ameliorates post-haemorrhagic hydrocephalus development after germinal matrix haemorrhage in neonatal rat pups. (United States)

    Klebe, Damon; Flores, Jerry J; McBride, Devin W; Krafft, Paul R; Rolland, William B; Lekic, Tim; Zhang, John H


    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-NH2 (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.

  16. Membrane properties of type II spiral ganglion neurones identified in a neonatal rat cochlear slice (United States)

    Jagger, Daniel J; Housley, Gary D


    Neuro-anatomical studies in the mammalian cochlea have previously identified a subpopulation of approximately 5% of primary auditory neurones, designated type II spiral ganglion neurones (sgnII). These neurones project to outer hair cells and their supporting cells, within the ‘cochlear amplifier’ region. Physiological characterization of sgnII has proven elusive. Whole-cell patch clamp of spiral ganglion neurones in P7-P10 rat cochlear slices provided functional characterization of sgnII, identified by biocytin or Lucifer yellow labelling of their peripheral neurite projections (outer spiral fibres) subsequent to electrophysiological characterisation. SgnII terminal fields comprised multiple outer hair cells and supporting cells, located up to 370 μm basal to their soma. SgnII firing properties were defined by rapidly inactivating A-type-like potassium currents that suppress burst firing of action potentials. Type I spiral ganglion neurones (sgnI), had shorter radial projections to single inner hair cells and exhibited larger potassium currents with faster activation and slower inactivation kinetics, compatible with the high temporal firing fidelity seen in auditory nerve coding. Based on these findings, sgnII may be identified in future by the A-type current. Glutamate-gated somatic currents in sgnII were more potentiated by cyclothiazide than those in sgnI, suggesting differential AMPA receptor expression. ATP-activated desensitising inward currents were comparable in sgn II and sgnI. These data support a role for sgnII in providing integrated afferent feedback from the cochlear amplifier. PMID:14561834

  17. Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein. (United States)

    Foster, Warren G; Younglai, Edward V; Boutross-Tadross, Odette; Hughes, Claude L; Wade, Michael G


    In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group received either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist, blinded to treatment groups, examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively, our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.

  18. Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine. (United States)

    Dornelas, Conceição Aparecida; Santos, Alessandra Marques Dos; Correia, Antonio Lucas Oliveira; Juanes, Camila de Carvalho; Coelho, João Paulo Ferreira; Cunha, Bianca Lopes; Maciel, André Vinicius Vieira; Jamacaru, Francisco Vagnaldo Fechine


    to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). apesar de

  19. Reproductive efficiency of rats whose mothers treated with lead acetate during lactation: role of vitamin E

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    W. H. Yousif


    Full Text Available Reproductive efficiency of young male and female rats yielded from mothers treated with lead acetate (10 mg/kg B.W and vitamin E as an antioxidant (500 mg/kg during lactation period was studied. 27 pregnant albino rats aged 4-5 months divided into 3 groups, the first group given 0.2 ml distilled water through oral intubations (control. The second group given lead acetate (10 mg/kg B.W, while the 3rd group given lead acetate (10 mg/kg B.W with vitamin E (500 mg/kg B.Wt. Lead acetate treatment did not cause significant difference (P>0.05 in young male rats body, testes, epididymal (head, tail, prostate gland, seminal vesicle weights, number of epidiymal sperms count, percentage of live/dead sperms and sperms abnormalities accompanied with a significant increase (P0.05 in ovary and uterus weights. Lead acetate with vit. E cause significant decrease (P<0.05 in body, testes, epididymal (head, body weights, number of epididymal sperm count, percentage of live/dead and sperm abnormalities. Concerning young female rats treated with lead acetate and vit E showed a significant decrease (P<0.05 in body, uterus weights with a significant increase (P<0.05 in the duration of vaginal opening. Histopathological study revealed changes in the testes such as desquemination in some epithelial lining of seminiferous tubules and sertoli cells. Undevelopment of localized area of some seminiferous tubules with blood vessels congestion in both testes and ovaries with hyperemia in ovarian stroma, increase in follicular cells, decrease in corpus luteum formation, degeneration of ovarian follicles and increase in ovarian adipose tissue. This study concluded that lead acetate can be transmitted through mother milk to their pups. The dose of lead acetate (10 mg/kg B.W was enough to make bad effects on both male and female reproductive systems. Vitamin E (as an antioxidant found to have no improving effect in treatment of lead acetate disturbances on reproductive systems of

  20. Effects of maternal ingestion of aroclor 1254 (PCB) on the development pattern of oxygen consumption and body temperature in neonatal rats

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    Seo, B.W.; Meserve, L.A. [Bowling Green State Univ., OH (United States)


    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.

  1. Intestinal NADPH oxidase 2 activity increases in a neonatal rat model of necrotizing enterocolitis.

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    Scott R Welak

    Full Text Available Necrotizing enterocolitis (NEC is a complication of prematurity. The etiology is unknown, but is related to enteral feeding, ischemia, infection, and inflammation. Reactive oxygen species production, most notably superoxide, increases in NEC. NADPH oxidase (NOX generates superoxide, but its activity in NEC remains unknown. We hypothesize that NOX-derived superoxide production increases in NEC. Newborn Sprague-Dawley rats were divided into control, formula-fed, formula/LPS, formula/hypoxia, and NEC (formula, hypoxia, and LPS. Intestinal homogenates were analyzed for NADPH-dependent superoxide production. Changes in superoxide levels on days 0-4 were measured. Inhibitors for nitric oxide synthase (L-NAME and NOX2 (GP91-ds-tat were utilized. RT-PCR for eNOS, NOX1, GP91phox expression was performed. Immunofluorescence studies estimated the co-localization of p47phox and GP91phox in control and NEC animals on D1, D2, and D4. NEC pups generated more superoxide than controls on D4, while all other groups were unchanged. NADPH-dependent superoxide production was greater in NEC on days 0, 3, and 4. GP91-ds-tat decreased superoxide production in both groups, with greater inhibition in NEC. L-NAME did not alter superoxide production. Temporally, superoxide production varied minimally in controls. In NEC, superoxide generation was decreased on day 1, but increased on days 3-4. GP91phox expression was higher in NEC on days 2 and 4. NOX1 and eNOS expression were unchanged from controls. GP91phox and p47phox had minimal co-localization in all control samples and NEC samples on D1 and D2, but had increased co-localization on D4. In conclusion, this study proves that experimentally-induced NEC increases small intestinal NOX activity. All components of NEC model are necessary for increased NOX activity. NOX2 is the major source, especially as the disease progresses.

  2. Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats


    Jing-Hua Wang; Bong-Soo Kim; Kyungsun Han; Hojun Ki