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Sample records for newborn rat brain

  1. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  2. The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Borisova, Ekaterina; Abakumov, Maxim; Gorin, Dmitry; Avramov, Latchezar; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Serov, Alexander; Pavlov, Alexey; Zinchenko, Ekaterina; Lychagov, Vlad; Navolokin, Nikita; Shirokov, Alexander; Maslyakova, Galina; Zhu, Dan; Luo, Qingming; Chekhonin, Vladimir; Tuchin, Valery; Kurths, Jürgen

    2016-01-01

    In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health. PMID:27378933

  3. Imaging of an inflammatory injury in the newborn rat brain with photoacoustic tomography.

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    Edgar Guevara

    Full Text Available BACKGROUND: The precise assessment of cerebral saturation changes during an inflammatory injury in the developing brain, such as seen in periventricular leukomalacia, is not well defined. This study investigated the impact of inflammation on locoregional cerebral oxygen saturation in a newborn rodent model using photoacoustic imaging. METHODS: 1 mg/kg of lipopolysaccharide(LPS diluted in saline or saline alone was injected under ultrasound guidance directly in the corpus callosum of P3 rat pups. Coronal photoacoustic images were carried out 24 h after LPS exposure. Locoregional oxygen saturation (SO2 and resting state connectivity were assessed in the cortex and the corpus callosum. Microvasculature was then evaluated on cryosection slices by lectin histochemistry. RESULTS: Significant reduction of SO2 was found in the corpus callosum; reduced SO2 was also found in the cortex ipsilateral to the injection site. Seed-based functional connectivity analysis showed that bilateral connectivity was not affected by LPS exposure. Changes in locoregional oxygen saturation were accompanied by a significant reduction in the average length of microvessels in the left cortex but no differences were observed in the corpus callosum. CONCLUSION: Inflammation in the developing brain induces marked reduction of locoregional oxygen saturation, predominantly in the white matter not explained by microvascular degeneration. The ability to examine regional saturation offers a new way to monitor injury and understand physiological disturbance non-invasively.

  4. Oxidative stress of brain and liver is increased by Wi-Fi (2.45GHz) exposure of rats during pregnancy and the development of newborns.

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    Çelik, Ömer; Kahya, Mehmet Cemal; Nazıroğlu, Mustafa

    2016-09-01

    An excessive production of reactive oxygen substances (ROS) and reduced antioxidant defence systems resulting from electromagnetic radiation (EMR) exposure may lead to oxidative brain and liver damage and degradation of membranes during pregnancy and development of rat pups. We aimed to investigate the effects of Wi-Fi-induced EMR on the brain and liver antioxidant redox systems in the rat during pregnancy and development. Sixteen pregnant rats and their 48 newborns were equally divided into control and EMR groups. The EMR groups were exposed to 2.45GHz EMR (1h/day for 5 days/week) from pregnancy to 3 weeks of age. Brain cortex and liver samples were taken from the newborns between the first and third weeks. In the EMR groups, lipid peroxidation levels in the brain and liver were increased following EMR exposure; however, the glutathione peroxidase (GSH-Px) activity, and vitamin A, vitamin E and β-carotene concentrations were decreased in the brain and liver. Glutathione (GSH) and vitamin C concentrations in the brain were also lower in the EMR groups than in the controls; however, their concentrations did not change in the liver. In conclusion, Wi-Fi-induced oxidative stress in the brain and liver of developing rats was the result of reduced GSH-Px, GSH and antioxidant vitamin concentrations. Moreover, the brain seemed to be more sensitive to oxidative injury compared to the liver in the development of newborns.

  5. Hyperbaric oxygen suppresses hypoxic-ischemic brain damage in newborn rats.

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    Zhu, Min; Lu, Mengru; Li, Qing-Jie; Zhang, Zhuo; Wu, Zheng-Zheng; Li, Jie; Qian, Lai; Xu, Yun; Wang, Zhong-Yuan

    2015-01-01

    The optimal therapeutic time-window and protective mechanism of hyperbaric oxygen in hypoxic-ischemic brain damage remain unclear. This study aimed to determine the neuroprotective effects of hyperbaric oxygen. Following hypoxic-ischemic brain damage modeling in neonatal rats, hyperbaric oxygen was administered at 6, 24, 48, and 72 hours and 1 week after hypoxia, respectively, once daily for 1 week. Fourteen days after hypoxic-ischemic brain damage, cell density and apoptosis rate, number of Fas-L+, caspase-8+, and caspase-3+ neuronal cells, levels of nitric oxide, malondialdehyde, and superoxide dismutase in hippocampus were examined. Morris water maze test was conducted 28 days after insult. Significant improvements were found in cell density, rate of apoptosis, oxidative stress markers, FasL, and caspases in rats treated with hyperbaric oxygen within 72 hours compared to hypoxic-ischemic injury. Similarly, time-dependent behavioral amelioration was observed in pups treated with hyperbaric oxygen. Our findings suggest that hyperbaric oxygen protects against hypoxic-ischemic brain damage by inhibiting oxidative stress and FasL-induced apoptosis, and optimal therapeutic time window is within 72 hours after hypoxic-ischemic brain damage.

  6. Assessment of genotoxic and cytotoxic hazards in brain and bone marrow cells of newborn rats exposed to extremely low-frequency magnetic field.

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    Rageh, Monira M; El-Gebaly, Reem H; El-Bialy, Nihal S

    2012-01-01

    The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF) and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery) were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA) and the activity of glutathione (GSH) and superoxide dismutase (SOD). The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P < 0.01, 0.001, 0.0001). Moreover ELF-MF exposure induced a significant (P < 0.01, 0.001) four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P < 0.0001). Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P < 0.05). Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  7. Assessment of Genotoxic and Cytotoxic Hazards in Brain and Bone Marrow Cells of Newborn Rats Exposed to Extremely Low-Frequency Magnetic Field

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    Monira M. Rageh

    2012-01-01

    Full Text Available The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA and the activity of glutathione (GSH and superoxide dismutase (SOD. The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P<0.01,0.001,0.0001. Moreover ELF-MF exposure induced a significant (P<0.01,0.001 four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P<0.0001. Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P<0.05. Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  8. Ketamine reduces the cell death following inflammatory pain in newborn rat brain.

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    Anand, Kanwaljeet J S; Garg, Sarita; Rovnaghi, Cynthia R; Narsinghani, Umesh; Bhutta, Adnan T; Hall, Richard W

    2007-09-01

    Premature infants experience untreated repetitive pain that may alter their brain development. Effects of ketamine and repetitive pain on cellular death and subsequent behavior were studied in neonatal rats. Rat pups were randomized to undisturbed controls (C), 4% formalin injection (F), ketamine alone (K, 5 mg/kg) or formalin plus ketamine (KF) and were assessed for neuroactivation with Fos protein, cellular death with FluoroJade-B, cognition with the radial arm maze, and pain thresholds with the hot-plate. Greater Fos expression and cell death occurred in F vs. C groups in defined brain areas at 1 and 4 h in F compared with other groups. Cell death was accentuated 3.3-fold in cortical areas and 1.6-fold in subcortical areas in the F compared with the C group following repetitive pain and sacrifice 18-20 h later. These effects were ameliorated by ketamine. Compared with the F group, all other groups demonstrated greater exploratory and rearing behaviors and decreased time for bait consumption at 1-h and 3-h intervals. Significantly greater thermal pain latencies occurred in the KF and F groups. Repetitive neonatal pain accentuates neuronal excitation and cell death in developmentally regulated cortical and subcortical areas, which decreases the acquisition of visual-spatial clues, short-term and long-term memory, and increases pain latencies. Ketamine analgesia mitigates most of these effects.

  9. Bcl-2 enhances the formation of newborn striatal long-projection neurons in adult rat brain after a transient ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Jian-Jun Guo; Fang Liu; Xiao Sun; Jun-Jie Huang; Ming Xu; Feng-Yan Sun

    2012-01-01

    Objective It has been reported that B-cell lymphoma 2 (Bcl-2) enhances neurogenesis as well as supporting axonal growth after injury.In the present study,we investigated whether Bcl-2 overexpression plays a role in the formation of newborn striatonigral projection neurons in the adult rat brain after transient middle cerebral artery occlusion (MCAO).Methods We infused human Bcl-2-expressing plasmid (pBcl-2) into the lateral ventricle immediately after 30 min of MCAO,injected 5'-bromodeoxyuridine (BrdU) intraperitoneally to label proliferative cells,and microinjected fluorogold (FG) into the substantia nigra at 11 weeks of reperfusion followed by multiple immunostaining of striatonigral projection neurons at 12 weeks.Results We found that pBcl-2 treatment significantly increased the number of newborn neurons (BrdU+-NeuN+) in the striatum ipsilateral to the MCAO.We further detected newborn striatonigral projection neurons (BrdU+-FG+-NeuN+) in the ipsilateral striatum at 12 weeks.More interestingly,the number of newborn striatonigral projection neurons (BrdU+-FG+) was significantly increased by pBcl-2 treatment compared to that by pEGFP,a control plasmid.Conclusion Taken together,we found that Bcl-2 overexpression in the brain enhanced the generation of newborn striatonigral projection neurons.This provides a potential strategy for promoting the reestablishment of neural networks and brain repair after ischemic injury.

  10. Traumatic brain lesions in newborns

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    Nícollas Nunes Rabelo

    Full Text Available ABSTRACT The neonatal period is a highly vulnerable time for an infant. The high neonatal morbidity and mortality rates attest to the fragility of life during this period. The incidence of birth trauma is 0.8%, varying from 0.2-2 per 1,000 births. The aim of this study is to describe brain traumas, and their mechanism, anatomy considerations, and physiopathology of the newborn traumatic brain injury. Methods A literature review using the PubMed data base, MEDLINE, EMBASE, Science Direct, The Cochrane Database, Google Scholar, and clinical trials. Selected papers from 1922 to 2016 were studied. We selected 109 papers, through key-words, with inclusion and exclusion criteria. Discussion This paper discusses the risk factors for birth trauma, the anatomy of the occipito-anterior and vertex presentation, and traumatic brain lesions. Conclusion Birth-related traumatic brain injury may cause serious complications in newborn infants. Its successful management includes special training, teamwork, and an individual approach.

  11. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  12. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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    Huang, Yuejun; Lai, Huihong; Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Chen, Yunbin; Ma, Lian

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  13. Prenatal malnutrition and lead intake produce increased brain lipid peroxidation levels in newborn rats.

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    Maldonado-Cedillo, Brenda Gabriela; Díaz-Ruiz, Araceli; Montes, Sergio; Galván-Arzate, Sonia; Ríos, Camilo; Beltrán-Campos, Vicente; Alcaraz-Zubeldia, Mireya; Díaz-Cintra, Sofia

    2016-09-01

    Prenatal malnutrition (M) and lead intoxication (Pb) have adverse effects on neuronal development; one of the cellular mechanisms involved is a disruption of the pro- and anti-oxidant balance. In the developing brain, the vulnerability of neuronal membrane phospholipids is variable across the different brain areas. This study assesses the susceptibility of different brain regions to damage by quitar tissue oxidative stress and lead quitar concentrations to determine whether the combined effect of prenatal malnutrition (M) and lead (Pb) intoxication is worse than the effect of either of them individually. M was induced with an isocaloric and hypoproteinic (6% casein) diet 4 weeks before pregnancy. Intoxication was produced with lead acetate in drinking water, from the first gestational day. Both the M and Pb models were continued until the day of birth. Four brain regions (hippocampus, cortex, striatum, and cerebellum) were dissected out to analyze the lipid peroxidation (LP) levels in four groups: normally nourished (C); normally nourished but intoxicated with lead (CPb); malnourished (M); and M intoxicated with lead (MPb). Dam body and brain weights were significantly reduced in the fourth gestational week in the MPb group. Their pups had significantly lower body weights than those in the C and CPb groups. The PbM group exhibited significant increases of lead concentration and LP in all areas evaluated. A potentiation effect of Pb and M on LP was found in the cerebellum. This study provides information on how environmental conditions (intoxication and malnutrition) during the intrauterine period could differentially affect the development of neuronal plasticity and, in consequence, alter adult brain functions such as learning and memory.

  14. Effects of Electric Acupuncture on Monoamine Neurotransmitters in Brains of Newborn Rats with Cerebral Palsy%电针对新生脑性麻痹大鼠单胺类神经递质的影响

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    林世坚; 刘振寰; 潘佩光; 赵勇; 祁岩超

    2009-01-01

    objective to detect the content of monoamine neurotransmitters in hippocampus, cortex, basal nucleus and the brainstem of newborn rats with cerebral palsy, to observe the effects of acupuncture on monoamine neurotransmitters, and to explore the mechanism of acupuncture treatment to newborn rats with cerebral palsy. Methods using the method of hypoxic ischemic to make the model of newborn rats with cerebral palsy,decapitating brain after giving acupuncture treatment, separating the required brain regions, and detecting the content of monoamine neurotransmitters with speetrophotometer.Results Compared with the sham operation group, the content of dopamine (DA), 5-Hydroxytryptamine (5-HT) in basal nucleus area of newborn rats with cerebral palsy, and norepinephrine (NE) in Brainstem area decreased significantly(P<0.05), which elevated ignificantly(P<0.05)afler acupuncture treatment. Conclusion it indicated that to improve the ontent of monoamine neurotransmitters in related brain areas may be one of the mechanisms in the acupuncture treatment of newborn rats with cerebral paraly.

  15. Electroacupuncture atBaihui (DU20) acupoint up-regulates mRNA expression of NeuroD molecules in the brains of newborn rats sufferingin utero fetal distress

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    Lu Chen; Yan Liu; Qiao-mei Lin; Lan Xue; Wei Wang; Jian-wen Xu

    2016-01-01

    NeuroD plays a key regulatory effect on differentiation of neural stem cells into mature neurons in the brain. Thus, we assumed that electroacupuncture atBaihui (DU20) acupoint in newborn rats exposed toin utero fetal distress would inlfuence expression of NeuroD. Electroacupuncture atBaihui was performed for 20 minutes on 3-day-old (Day 3) newborn Sprague-Dawley rats exposed toin utero fetal distress; electroacupuncture parameters consisted of sparse and dense waves at a frequency of 2–10 Hz. Real-time lfuorescent quantitative PCR results demonstrated that mRNA expression of NeuroD, a molecule that indicates NeuroD, increased with prolonged time in brains of newborn rats, and peaked on Day 22. The level of mRNA expression was similar between Day 16 and Day 35. These ifndings suggest that electro acupuncture atBaihui acupoint could effectively increase mRNA expression of molecules involved in NeuroD in the brains of new-born rats exposed to in utero fetal distress.

  16. Interventional effect of laser acupoint radiation on the expression of Nissl body and brain-derived neurotrophic factor in newborn rat models with ischemic/hypoxic cerebral injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Some researches report that He-Ne laser can activate function of erythrocytes and increase content of blood and oxygen via bio-stimulating effect;therefore,it suspects that laser radiation at Baihui and Dazhui can partially increase blood circulation for oxygen-supplying content of brain and improve functional status of neurons.OBJECTIVE:To verify the effects of laser radiation at Baihui and Dazhui on the expression of Nissl body of brain tissue neurons and brain-derived neurotrophic factor (BDNF) in newborn rats with ischemic/hypoxic cerebral injury.DESIGN:Randomized controlled animal study.SETTING:Department of Neurological Histochemistry,Xianning University.MATERIALS:Forty Wistar rats of 7 - 8 days old,weighing 15 - 20 g and of both genders,were selected from Wuhan Experimental Animal Center.All the rats were randomly divided into sham operation group (n =8),model group (n =16) and radiation group (n =16).The experimental animals were disposed according to ethical criteria.BDNF kit was provided by Wuhan Boster Bioengineering Co.,Ltd.METHODS:The experiment was carried out in the Department of Neurological Histochemistry,Xianning University from April 2005 to October 2006.Rats in the radiation group and model group were performed with ligation of left common carotid artery,recovered at room temperature for 1-6 days,maintained in self-made hypoxic cabin under normal pressure and injected mixture gas (0.05 volume fraction of O2 and 0.92 volume fraction of N2) for 2 hours.In addition,rats in the sham operation group were treated with separation of left common carotid artery but not ligation and hypoxia.Rats in the model group were not given any treatment;while,rats in the radiation group were exposed with He-Ne laser of 63.28 nm in the wave length at Baihui and Dazhui acupoints on the second day after ischemia-hypoxia.The radiation was given for 10 minutes per day and once a day.Ten days were regarded as a course and the rats were exposed for 2 courses in

  17. Low Blood Sugar in Newborns Tied to Brain Problems Later

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    ... medlineplus.gov/news/fullstory_167671.html Low Blood Sugar in Newborns Tied to Brain Problems Later These ... TUESDAY, Aug. 8, 2017 (HealthDay News) -- Low blood sugar affects about one in six newborns, and new ...

  18. Nerve protective effect of Baicalin on newborn HIBD rats

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    Objective:To investigate the nerve protective effect and mechanism of baicalin on newborn rats with hypoxic ischemic brain damage(HIBD).Methods:A total of64SD newborn rats were randomly divided into control group, model group, nerve growth factor group and baicalin group, with16 in each group.Left carotid artery ligation method was adopted to establish theHIBD model except for in control group, which was treated with intraperitoneal injection of salin e10 mL/kg for3 d.After oxygen recovery on hypoxia ischemia rats, intraperitoneal injection of saline10 mL/kg was adopted in model group for3 d.Intraperitoneal injection of nerve growth factor injection 50μg/kg per day was adopted in nerve growth factor group for3 d; intraperitoneal injection of radix scutellariae16 mg/kg per day was adopted in baicalin group for3 d after modeling.Four rats of each group were sacrificed atDay1,2,3,7 for microscopic observation of pathological morphological changes in brain tissue afterHE staining,S-P immunohistochemical method was used for observation ofFas andFasL expression in brain cells.Results:Neat structure of cells was observed in control group; edema cells in disordered arrangement was observed in model group, with some cells necrosis and cavity change; tissue injury in nerve growth factor group and baicalin group was significantly lighter than that in model group;Fas andFasL expression in model group, nerve growth factor group and baicalin group were significantly higher than that in control group at different time points(P0.05).Conclusions:Baicalin can reduce expression ofFas andFasL inHIBD rats, inhibit apoptosis of nerve cells, thus achieve the protective effect onHIBD rat nerves.

  19. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

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    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  20. Monitoring of newborns at high risk for brain injury

    OpenAIRE

    Pisani, Francesco; Spagnoli, Carlotta

    2016-01-01

    Due to the increasing number of surviving preterm newborns and to the recognition of therapeutic hypothermia as the current gold standard in newborns with hypoxic-ischaemic encephalopathy, there has been a growing interest in the implementation of brain monitoring tools in newborns at high risk for neurological disorders. Among the most frequent neurological conditions and presentations in the neonatal period, neonatal seizures and neonatal status epilepticus, paroxysmal non-epileptic motor p...

  1. Neonatal handling on the first postnatal day leads to increased maternal behavior and fos levels in the brain of the newborn rat.

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    Garoflos, Efstathios; Stamatakis, Antonios; Rafrogianni, Androniki; Pondiki, Stavroula; Stylianopoulou, Fotini

    2008-11-01

    In the present work we employed Fos expression, an index of neuronal activity, to identify brain areas activated by a single exposure to "neonatal handling" on postnatal Day 1. Eight hours following "handling" there was an increase in the number of Fos positive cells in the hippocampus, the parietal and occipital cortex. We also recorded maternal behavior during the 8 hr following "handling." "Handled" pups received increased maternal licking during the 4 hr following the end of "handling." Furthermore, the number of Fos positive cells detected in each of the three brain areas 8 hr following "handling" was positively correlated with the amount of licking up to 8 hr following "handling." These results indicate that the increased maternal care could underlie the handling-induced increase in Fos. The Fos protein, acting as a transcription factor, controls the expression of downstream genes, whose products may mediate the effects of "neonatal handling" on the developing rat brain.

  2. Effects of corticotropin releasing factor on spontaneous burst activity in the piriform-amygdala complex of in vitro brain preparations from newborn rats.

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    Fujii, Tomoko; Onimaru, Hiroshi; Homma, Ikuo

    2011-10-01

    The amygdala is an important higher regulatory center of the autonomic nervous system, involved in respiratory and cardiovascular control, and it also plays a role in the formation of emotions. Corticotropin-releasing factor (CRF) is a neuropeptide involved in stress responses. We have examined the effects of CRF on the spontaneous burst activity in the piriform-amygdala complex of rat brain preparations in vitro. Limbic-brainstem-spinal cord preparations of 0- to 1-day-old Wistar rats were isolated under deep ether anesthesia, and were superperfused in a modified Krebs solution. Bath application of 50nM CRF substantially increased the frequency of burst activity in the piriform-amygdala complex, whereas this polypeptide exerted only minor effects on C4 inspiratory activity. The excitatory effect of CRF on the amygdala burst was effectively blocked by the CRF1 antagonist, antalarmin, but not the CRF2 antagonist, astressin-2B, suggesting that CRF1 mediated the excitatory effect. The spatio-temporal pattern of the burst activity according to optical recordings was basically identical to the controls; the burst activity initially appeared in the piriform cortex and then propagated to the amygdala. The present experimental model could be useful for the study of role of the limbic system, including the amygdala, in stress responses.

  3. Rapid whisker movements in sleeping newborn rats.

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    Tiriac, Alexandre; Uitermarkt, Brandt D; Fanning, Alexander S; Sokoloff, Greta; Blumberg, Mark S

    2012-11-06

    Spontaneous activity in the sensory periphery drives infant brain activity and is thought to contribute to the formation of retinotopic and somatotopic maps. In infant rats during active (or REM) sleep, brainstem-generated spontaneous activity triggers hundreds of thousands of skeletal muscle twitches each day; sensory feedback from the resulting limb movements is a primary activator of forebrain activity. The rodent whisker system, with its precise isomorphic mapping of individual whiskers to discrete brain areas, has been a key contributor to our understanding of somatotopic maps and developmental plasticity. But although whisker movements are controlled by dedicated skeletal muscles, spontaneous whisker activity has not been entertained as a contributing factor to the development of this system. Here we report in 3- to 6-day-old rats that whiskers twitch rapidly and asynchronously during active sleep; furthermore, neurons in whisker thalamus exhibit bursts of activity that are tightly associated with twitches but occur infrequently during waking. Finally, we observed barrel-specific cortical activity during periods of twitching. This is the first report of self-generated, sleep-related twitches in the developing whisker system, a sensorimotor system that is unique for the precision with which it can be experimentally manipulated. The discovery of whisker twitching will allow us to attain a better understanding of the contributions of peripheral sensory activity to somatosensory integration and plasticity in the developing nervous system. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  5. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Qiu-Wan Zhang

    Full Text Available Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function. Exercise training post-stroke improves motor recovery in clinic patients and increases striatal neurogenesis in experimental animals. This study aimed to investigate the effects of exercise on axon regeneration of newborn projection neurons in adult rat brains following ischemic stroke. Rats were subjected to a transient MCAO to induce focal cerebral ischemic injury, followed by 30 minutes of exercise training daily from 5 to 28 days after MCAO. Motor function was tested using the rotarod test. We used fluorogold (FG nigral injection to trace striatonigral and corticonigral projection neurons, and green fluorescent protein (GFP-targeting retroviral vectors combined with FG double labeling (GFP(+ -FG(+ to detect newborn projection neurons. The results showed that exercise improved the recovery of motor function of rats after MCAO. Meanwhile, exercise also increased the levels of BDNF and VEGF, and reduced Nogo-A in ischemic brain. On this condition, we further found that exercise significantly increased the number of GFP(+ -FG(+ neurons in the striatum and frontal and parietal cortex ipsilateral to MCAO, suggesting an increase of newborn striatonigral and corticonigral projection neurons by exercise post-stroke. In addition, we found that exercise also increased NeuN(+ and FG(+ cells in the striatum and frontal and parietal cortex, the ischemic territory, and tyrosine hydroxylase (TH immunopositive staining cells in the substantia nigra, a region remote from the ischemic territory. Our results provide the first evidence that exercise can effectively enhance the capacity for regeneration of newborn projection neurons in ischemic injured mammalian brains while improving motor function. Our results provide a very important cellular mechanism

  6. Brain vein disorders in newborn infants

    NARCIS (Netherlands)

    Raets, Marlou; Dudink, Jeroen; Raybaud, Charles; Ramenghi, Luca; Lequin, Maarten; Govaert, Paul

    2015-01-01

    The brain veins of infants are in a complex phase of remodelling in the perinatal period. Magnetic resonance venography and susceptibility-weighted imaging, together with high-resolution Doppler ultrasound, have provided new tools to aid study of venous developmental anatomy and disease. This review

  7. Brain Injury Following Repetitive Apnea in Newborn Piglets

    Science.gov (United States)

    Schears, Gregory; Creed, Jennifer; Antoni, Diego; Zaitseva, Tatiana; Greeley, William; Wilson, David F.; Pastuszko, Anna

    Repetitive apnea is associated with a significant increase in extracellular dopamine, generation of free radicals as determined by o-tyrosine formation and increase in Fluoro-Jade staining of degenerating neurons. This increase in extracellular dopamine and of hydroxyl radicals in striatum of newborn brain is likely to be at least partly responsible for the neuronal injury and neurological side effects of repetitive apnea.

  8. Developmental venous anomaly in the newborn brain

    Energy Technology Data Exchange (ETDEWEB)

    Horsch, S. [Erasmus MC-Sophia Children' s Hospital, Department of Neonatology, Rotterdam (Netherlands); Helios Klinikum Berlin-Buch, Department of Neonatology, Berlin (Germany); Govaert, P. [Erasmus MC-Sophia Children' s Hospital, Department of Neonatology, Rotterdam (Netherlands); Cowan, F.M. [Hammersmith Hospital, Department of Paediatrics, Imperial College Healthcare NHS Trust, London (United Kingdom); Benders, M.J.N.L.; Groenendaal, F.; Vries, L.S. de [University Medical Centre Utrecht, Wilhelmina Children' s Hospital, Department of Neonatology, Utrecht (Netherlands); Lequin, M.H. [Erasmus MC/Sophia Children' s Hospital, Department of Paediatric Radiology, Rotterdam (Netherlands); Saliou, G. [University Hospital, Department of Neuroradiology, Le Kremlin-Bicetre (France)

    2014-07-15

    Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age. (orig.)

  9. 新生期注射谷氨酸单钠对大鼠脑区损伤程度的比较观察%Comparative Study of Damage to Different Parts of Brain with Injected Monosodium Glutamate in Newborn Rat

    Institute of Scientific and Technical Information of China (English)

    张金平; 史玉兰; 金凤霞; 白文忠; 高志国

    2000-01-01

    The damage to 16 parts of brain is comparatively researched in the adult rat. Those experimental animals are injected intraperitoneal different dose monosodium glutamate in the newborn period. The neurons are decrease markedly in most parts of the brain in the experimental rats. But some parts of brain are protected from the neurotoxicity of monosodium glutamate.%比较观察了在新生期腹腔内注射不同剂量谷氨酸单钠后,成年大鼠16个脑区的神经元损伤程度.发现大多数脑区的神经元显著减少,但有的脑区对谷氨酸单钠的神经毒性具有一定保护作用.

  10. Considering ethical dilemmas related to brain death in newborns

    Directory of Open Access Journals (Sweden)

    Ilias Chatziioannidis

    2014-01-01

    Full Text Available Brain death (BD, as the irreversible and permanent loss of cerebral and brainstem function, is relatively uncommon among newborns who need life support. It is considered the result of an acute and irreversible central nervous system insult. Asphyxia, severe intracranial hemorrhage and infection are the most common causes of  BD in children. BD diagnosis is usually based on clinical criteria. Dilemmas about life prolonging treatment for severely compromised infants – as brain dead infants are – has become challenging since neonatal intensive care unit (NICU care has developed, quality of life and resource issues are nowadays continuously underlined. Caring for premature babies is expensive and costs have risen especially since an increased number of infants with handicaps survives. Intensivists’ main duty is first to save lives and then to interrupt treatment in certain conditions like detrimental brain damage. The objective of this article is to present ethical decisions regarding brain dead newborns in order to balance between organ donation necessities and withholding/withdrawing treatment, with respect to the important role of infants’ parents in the process.

  11. Rapid whisker movements in sleeping newborn rats

    National Research Council Canada - National Science Library

    Tiriac, Alexandre; Uitermarkt, Brandt D; Fanning, Alexander S; Sokoloff, Greta; Blumberg, Mark S

    2012-01-01

    .... The rodent whisker system, with its precise isomorphic mapping of individual whiskers to discrete brain areas, has been a key contributor to our understanding of somatotopic maps and developmental plasticity...

  12. Functional specializations for music processing in the human newborn brain.

    Science.gov (United States)

    Perani, Daniela; Saccuman, Maria Cristina; Scifo, Paola; Spada, Danilo; Andreolli, Guido; Rovelli, Rosanna; Baldoli, Cristina; Koelsch, Stefan

    2010-03-09

    In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the right auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance.

  13. Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?

    Institute of Scientific and Technical Information of China (English)

    Yan Ho Chan; Mingyong Gao; Wutian Wu

    2013-01-01

    Lead ion (Pb2+) has been proven to be a neurotoxin due to its neurotoxicity on mammalian nervous system, especially for the developing brains of juveniles. However, many reported studies involved the negative effects of Pb2+ on adult neural cells of humans or other mammals, only few of which have examined the effects of Pb2+ on neural stem cells. The purpose of this study was to reveal the biological effects of Pb2+ from lead acetate [Pb (CH3COO)2] on viability, proliferation and differentiation of neural stem cells derived from the hippocampus of newborn rats aged 7 days and adult rats aged 90 days, respectively. This study was carried out in three parts. In the first part, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT viability assay) was used to detect the effects of Pb2+ on the cell viability of passage 2 hippocampal neural stem cells after 200 μM Pb2+, followed by immunocytochemical staining with anti-bromodeoxyuridine to demonstrate the effects of Pb2+ on cell proliferation. In the last part, passage 2 hippocampal neural Immunocytochemical staining with anti-microtubule-associated protein 2 (a neuron marker), anti-glial fibrillary acidic protein (an astrocyte marker), and anti-RIP (an oligodendrocyte marker) was performed to detect the differentiation commitment of affected neural stem cells after 6 days. The data showed that Pb2+ inhibited not only the viability and proliferation of rat hippocampal neural stem cells, but also their neuronal and oligodendrocyte differentiation in vitro. Moreover, increased activity of astrocyte differentiation of hippocampal neural stem cells from both newborn and adult rats was observed after exposure to high concentration of lead ion in vitro. These findings suggest that hippocampal neural stem cells of newborn rats were more sensitive than those from adult rats to Pb2+ cytotoxicity.

  14. Transplantation of embryonic porcine neocortical tissue into newborn rats

    DEFF Research Database (Denmark)

    Castro, Anthony J; Meyer, Morten; Møller Dall, Annette

    2003-01-01

    Several previous studies, suggesting the potential use of embryonic xenografts in the treatment of neurological disorders, indicate that neural growth and axonal guidance factors may function across species. In this light, blocks of fetal porcine neocortex were grafted into small cortical lesion...... cavities made in newborn rats. Sacrifice at 3-12.5 weeks posttransplantation revealed healthy looking grafts in several animals. Apparent graft rejection evidenced by areas of necrosis and OX1 reactivity was observed in some of the older transplants. Treatment of nursing mothers or of postweaning newborns...... with cyclosporin A did not appear to promote graft survival. Some transplants grew to extremely large proportions and were characterized by bands of cells and bundles of axons as observed using immunohistochemical staining for pig neurofilament. Neurofilament-positive axons projected from several of the grafts...

  15. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Science.gov (United States)

    Torres-Mendoza, Blanca Miriam; Coronado-Medina, Damharis Elizabeth; Vázquez-Valls, Eduardo; Zamora-Perez, Ana Lourdes; Lemus-Varela, María de Lourdes

    2014-01-01

    The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses. PMID:24977162

  16. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Directory of Open Access Journals (Sweden)

    Blanca Miriam Torres-Mendoza

    2014-01-01

    Full Text Available The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE, micronucleated polychromatic erythrocytes (MNPCE, and polychromatic erythrocytes (PCE in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control, or 0.5 ml of sterile water (negative control. In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses.

  17. Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats.

    Science.gov (United States)

    Mori, M; Wilber, J F; Nakamoto, T

    1984-12-17

    We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.

  18. Therapeutic administration of plasminogen activator inhibitor-1 prevents hypoxic-ischemic brain injury in newborns.

    Science.gov (United States)

    Yang, Dianer; Nemkul, Niza; Shereen, Ahmed; Jone, Alice; Dunn, R Scott; Lawrence, Daniel A; Lindquist, Diana; Kuan, Chia-Yi

    2009-07-08

    Disruption of the integrity of the blood-brain barrier (BBB) is an important mechanism of cerebrovascular diseases, including neonatal cerebral hypoxia-ischemia (HI). Although both tissue-type plasminogen activator (tPA) and matrix metalloproteinase-9 (MMP-9) can produce BBB damage, their relationship in neonatal cerebral HI is unclear. Here we use a rodent model to test whether the plasminogen activator (PA) system is critical for MMP-9 activation and HI-induced brain injury in newborns. To test this hypothesis, we examined the therapeutic effect of intracerebroventricular injection of plasminogen activator inhibitor-1 (PAI-1) in rat pups subjected to unilateral carotid artery occlusion and systemic hypoxia. We found that the injection of PAI-1 greatly reduced the activity of both tPA and urokinase-type plasminogen activator after HI. It also blocked HI-induced MMP-9 activation and BBB permeability at 24 h of recovery. Furthermore, magnetic resonance imaging and histological analysis showed the PAI-1 treatment reduced brain edema, axonal degeneration, and cortical cell death at 24-48 h of recovery. Finally, the PAI-1 therapy provided a dose-dependent decrease of brain tissue loss at 7 d of recovery, with the therapeutic window at 4 h after the HI insult. Together, these results suggest that the brain PA system plays a pivotal role in neonatal cerebral HI and may be a promising therapeutic target in infants suffering hypoxic-ischemic encephalopathy.

  19. 外源性血管内皮生长因子基因对新生鼠缺氧缺血性脑损伤脑细胞凋亡的影响%Effect of exogenesis vascular endothelial growth factor gene on the apoptosis of brain cells in the HIBD of newborn rats

    Institute of Scientific and Technical Information of China (English)

    冀红; 徐立新; 曲云霞; 王中波

    2010-01-01

    目的 探讨外源性血管内皮生长因子(VEGF)基因对新生鼠缺氧缺血性脑损伤(HIBD)脑细胞凋亡的影响.方法 将36只7日龄新生大鼠随机分为对照组和治疗组,制备HIBD大鼠模型,经前囟分别注射空载质粒PCDNA 3.1和负载VEGF 120 cDNA的质粒PCDNA 3.1(100μg/只),应用流式细胞仪检测脑细胞的凋亡情况.结果 治疗组的脑细胞凋亡率为8.93±0.332,明显低于对照组的17.505±0.949,差异有非常显著性(P<0.01).结论 外源性VEGF可以减少脑细胞的凋亡,可能成为治疗HIBD的一条新途径.%Objective To explore the effect of exogenesis VEGF 120 gene on the apoptosis of brain cells in the HIBD of newborn rats. Methods VEGF eukaryotic expression plasmid (pCDNA 3.1/r VEGF 120) was constructed by cloning rat VEGF 120 cDNA into eukaryotic expression vector pCDNA 3.1. The HIBD model was established with seven days old SD rats,and all rats were diveded into two groups at random :contral group 18 rats( every rat model was injected pCDNA 3.1 100 μg immediately after hypoxia-is-chemic.then raised seven days) and therapy group 18 rats (every rat model was injected pCDNA 3.1/ rVEGF 120 100 μg immediately after hypoxia-ischemic). Flow cytometer( FCM) was used to detect the ratio of apoptosis of brain cell. Results There was a significant decrease in the ratio of apoptosis brain cells( control group 17.505 ± 0.949; therapy group 8.93 ± 0. 332). Conclusion The VEGF gene product can reduce apoptosis of brain cells.

  20. The neuroprotective effect of astaxanthin on newborn rat models of hypoxic-ischemic brain damage%虾青素对缺氧缺血性脑损伤新生大鼠模型的神经保护作用

    Institute of Scientific and Technical Information of China (English)

    林良烽

    2015-01-01

    背景:研究发现虾青素有良好的神经保护作用,但是对于其在新生儿缺氧缺血性损伤中的治疗作用,目前尚无相关报道。目的:构建缺氧缺血性脑损伤新生大鼠模型,观察虾青素对其产生的神经保护作用及作用的途径。方法:从98只7 d龄的SD乳鼠中随机取30只作为假手术组,其余大鼠结扎左颈总动脉2 h后,置于体积分数92%的特种标准气体、8%的氧气缺氧舱2 h建立缺血缺氧性脑损伤模型。假手术组仅分离颈总动脉,不予缺血缺氧处理。将造模成功的大鼠随机分为脑缺血缺氧组和虾青素治疗组,各30只。虾青素治疗组大鼠在脑缺血缺氧模型建成后立即通过腹腔注射80 mg/kg虾青素。结果与结论:与假手术组相比,脑缺血缺氧组大鼠缺血损伤区顶叶皮质中p-Akt、p-GSK3β、cleaved-caspase3蛋白的表达水平显著增加,Bcl-2蛋白的表达水平显著减少(P <0.05);与脑缺血缺氧组相比,虾青素治疗可以显著减少凋亡相关蛋白cleaved-caspase3蛋白的表达水平(P <0.05),显著上调Bcl-2蛋白的表达水平(P <0.05),明显减少凋亡细胞的数量(P <0.05)。提示虾青素可以显著改善新生大鼠缺氧缺血性脑损伤的预后及作用途径与上调Akt/GSK3β信号通路相关。%BACKGROUND:Several studies have demonstrated that astaxanthin has a good neuroprotective effect; however, the treatment effects of astaxanthin on newborns with hypoxic-ischemic brain damage have not been reported. OBJECTIVE: To build newborn rat models of hypoxic-ischemic brain damage, and investigate the neuroprotective effects of astaxanthin and the ways of action. METHODS: Thirty newborn Sprague-Dawley rats aged 7 days out of 98 were randomly taken as sham-operated group. The rest of rats were subjected to ligature of the left carotid artery for 2 hours and then placed in the hypoxic box containing 92% special standard gas and 8% oxygen to establish

  1. Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum on the brain development of newborn rats Influencia de los ácidos grasos omega-3 de la linaza (Linum usitatissimum en el desarrollo del cerebro de ratas recién nacidas

    Directory of Open Access Journals (Sweden)

    K. C. Lenzi Almeida

    2011-10-01

    Full Text Available Objectives: The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Material and methods: Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n = 6, FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Results: Significant increase in brain weight (39% and relative brain weight (37% was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3 fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA (38%, as well as in total of omega-3 (n-3 fatty acids (62%. Conclusion: Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.Objetivos: La importancia de los ácidos grasos esenciales, en particular la familia omega-3, en el desarrollo del sistema nervioso central de los recién nacidos está bien documentada. La semilla de linaza (Linum usitatissimum es considerada una de las mejores fuentes vegetales de ácidos grasos omega-3. Se evaluó la influencia de los ácidos grasos omega-3 de la linaza en el desarrollo del cerebro de ratas recién nacidas. Material y métodos: Las crías de la generación F1 se obtuvieron a partir de 18 ratas Wistar divididas en 3 grupos (n = 6, GL: alimentados con dieta a base de linaza adicionada con caseína, GC: a

  2. Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Bin Sun; Xing Feng; Xin Ding; Li Bao; Yongfu Li; Jun He; Meifang Jin

    2012-01-01

    Clock genes are involved in circadian rhythm regulation,and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal.This study aimed to determine the expression of the clock genes Clock and Bmall,in the pineal gland of rats with hypoxic-ischemic brain damage.Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia.Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours.The levels of Bmall mRNA reached a peak at 36 hours,but were significantly reduced at 48 hours.Experimental findings indicate that Clock and Bmall genes were indeed expressed in the pineal glands of neonatal rats.At the initial stage (within 36 hours) of hypoxic-ischemic brain damage,only slight changes in the expression levels of these two genes were detected,followed by significant changes at 36 48 hours.These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.

  3. Features of microelement maintenance in rat's brain tissues at experimental hypoxia of different degree.

    Directory of Open Access Journals (Sweden)

    Tarasova I.V.

    2011-01-01

    Full Text Available Features of microelement maintenance (iron, zinc, copper, manganese, and cobalt, conditionally toxic chrome and toxic lead were studied in newborn rat's brain tissues at experimental hypoxia of different degree. Tissues of newborn rat’s brain are characterized by high level of saturation and considerable dynamism of microelement maintenance. Till the end of the first week of life, the maintenance of these microelements decreases in 1,5 – 10 times. The level of the toxic lead decreases more than in 2,5 times. The hypoxia of easy degree of newborn rats invokes reduction cobalt level 3 times, iron level 2 times, manganese – on 27,65 %, chrome – on 25,84%, zinc – on 16,43%. It means that considerable deficiency and disbalance of microelement maintenance rat's brain tissues. The heavy degree of hypoxia is characterized by further increase of deficiency and disbalance of microelements.

  4. Pseudomonas Sepsis and Multiple Brain Abscesses in a Newborn Infant Following Neurosurgical Procedure for Meningocele

    Directory of Open Access Journals (Sweden)

    Bilgili Gökmen

    2015-10-01

    Full Text Available Introduction: Postneurosurgical brain abscess carries a high risk of neurologic morbidity and mortality. Case Presentation: A newborn infant had Pseudomonas sepsis and multiple brain abscesses after meningocele repair, and was successfully treated medically. Conclusion: Prompt recognition of this life-threatening condition is crucial.

  5. Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats.

    Directory of Open Access Journals (Sweden)

    So Yoon Ahn

    Full Text Available Recently, we showed that intracerebroventricular (IC transplantation of human umbilical cord blood (UCB-derived mesenchymal stem cells (MSCs significantly attenuates posthemorrhagic hydrocephalus (PHH and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4. After confirming severe IVH with brain magnetic resonance imaging (MRI at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×105, an IV route (5×105, or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

  6. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats.

    Science.gov (United States)

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2014-06-01

    Astrocytes are responsible for modulating neurotransmitter systems and synaptic information processing, ionic homeostasis, energy metabolism, maintenance of the blood-brain barrier, and antioxidant and inflammatory responses. Our group recently published a culture model of cortical astrocytes obtained from adult Wistar rats. In this study, we established an in vitro model for hippocampal astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats. Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and neuroprotective effects that modulate glial functions. Here, we evaluated the effects of resveratrol on GSH content, GS activity, TNF-α and IL-1β levels in hippocampal astrocytes from newborn, adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an increase in the inflammatory response in hippocampal astrocytes from adult and aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol prevented these effects. These findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with antioxidant and anti-inflammatory activities.

  7. Balb/C鼠尾胶原与大鼠尾胶原对新生Balb/C鼠脑细胞培养的影响%Effects of Balb/C mouse tail collagen and rat tail collagen on newborn Balb/C mouse brain cells in culture

    Institute of Scientific and Technical Information of China (English)

    赵兰娟; 龚蕴贞; 林维芬; 胡涛; 张咏南

    2001-01-01

    目的确定鼠脑细胞体外培养的适宜生长基质。方法以Balb/C鼠尾胶原与大鼠尾胶原作为生长基质,培养新生Balb/C鼠脑细胞。结果 Balb/C鼠尾胶原有利于神经元的生存、生长与分化,而大鼠尾胶原则利于星形胶质细胞的生存、生长、分化与增殖。结论 2种鼠尾胶原均为培养鼠脑细胞适宜的生长基质,培养1个月左右宜用Balb/C鼠尾胶原而长期培养则宜选择大鼠尾胶原。%Objective To determine the suitable growth substrate for brain cells in culture. Methods Two kinds of collagen from Balb/C mouse tail and rat tail respectively as growth substrate was applied to culturing newborn Balb/C mouse brain cells. Results Balb/C mouse tail collagen was suitable to the survival, growth, differentiation of neurons, whereas rat tail collagen those of astrocytes. Conclusion Two kinds of collagen are suitable as growth substrate of neuron culture. Balb/C mouse tail collagen may be applied as growth substrate for short-term cultures, whereas rat tail collagen may be adopted for long-term cultures.

  8. Prenatal Exposure to Nicotine in Pregnant Rat Increased Inflammatory Marker in Newborn Rat

    Directory of Open Access Journals (Sweden)

    Yosouf Mohsenzadeh

    2014-01-01

    Full Text Available This study aimed to investigate any inflammatory effect of nicotine on rat embryo by exposing their mothers to different dosages of nicotine during pregnancy. During this experimental study, 32 pregnant healthy Wistar rats were divided into 4 equal groups, including a control and 3 nicotine exposure groups. Injections were performed subcutaneously starting at the first day of pregnancy until parturition. As the dosages of nicotine were increased, the weight gain by pregnant rats and the mean weight of their newborns were significantly reduced. Mean ± SD of hs-CRP was significantly higher among groups exposed to various dosages of nicotine (2, 4, and 6 mg/kg compared to the control group (P<0.0001 and its increasing rate was also dose dependent. Mean ± SD serum level of IL-6 and TNF-α among all groups exposed to nicotine, except for 2 mg/kg nicotine injected group, was increased significantly (P<0.0001. Mean ± SD of serum level of TGF-β and nitrite oxide among exposure groups showed significant differences compared to the control group only at the dosage of 6 mg/kg (P<0.0001. The current study showed that exposing pregnant rats to nicotine causes a dose dependent increase in the rate of all the studied inflammatory serum markers among their newborns.

  9. Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

    Science.gov (United States)

    Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke

    2014-10-01

    Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the

  10. A portable near infrared spectroscopy system for bedside monitoring of newborn brain

    Directory of Open Access Journals (Sweden)

    Rosen Harel

    2005-04-01

    Full Text Available Abstract Background Newborns with critical health conditions are monitored in neonatal intensive care units (NICU. In NICU, one of the most important problems that they face is the risk of brain injury. There is a need for continuous monitoring of newborn's brain function to prevent any potential brain injury. This type of monitoring should not interfere with intensive care of the newborn. Therefore, it should be non-invasive and portable. Methods In this paper, a low-cost, battery operated, dual wavelength, continuous wave near infrared spectroscopy system for continuous bedside hemodynamic monitoring of neonatal brain is presented. The system has been designed to optimize SNR by optimizing the wavelength-multiplexing parameters with special emphasis on safety issues concerning burn injuries. SNR improvement by utilizing the entire dynamic range has been satisfied with modifications in analog circuitry. Results and Conclusion As a result, a shot-limited SNR of 67 dB has been achieved for 10 Hz temporal resolution. The system can operate more than 30 hours without recharging when an off-the-shelf 1850 mAh-7.2 V battery is used. Laboratory tests with optical phantoms and preliminary data recorded in NICU demonstrate the potential of the system as a reliable clinical tool to be employed in the bedside regional monitoring of newborn brain metabolism under intensive care.

  11. Language and the newborn brain: Does prenatal language experience shape the neonate neural response to speech?

    OpenAIRE

    Lillian eMay; Krista eByers-Heinlein; Judit eGervain; Werker, Janet F.

    2011-01-01

    Previous research has shown that by the time of birth, the neonate brain responds specially to the native language when compared to acoustically similar non-language stimuli. In the current study, we use Near Infrared Spectroscopy to ask how prenatal language experience might shape the brain response to language in newborn infants. To do so, we examine the neural response of neonates when listening to familiar versus unfamiliar language, as well as to non-linguistic backwards language. Twenty...

  12. Language and the Newborn Brain: Does Prenatal Language Experience Shape the Neonate Neural Response to Speech?

    OpenAIRE

    May, Lillian; Byers-Heinlein, Krista; Gervain, Judit; Werker, Janet F.

    2011-01-01

    Previous research has shown that by the time of birth, the neonate brain responds specially to the native language when compared to acoustically similar non-language stimuli. In the current study, we use near-infrared spectroscopy to ask how prenatal language experience might shape the brain response to language in newborn infants. To do so, we examine the neural response of neonates when listening to familiar versus unfamiliar language, as well as to non language stimuli. Twenty monolingual ...

  13. Effects of sevoflurane and isoflurane on neuroapoptosis and the long-term learning ability in newborn rat brain%七氟烷、异氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响

    Institute of Scientific and Technical Information of China (English)

    斯小龙; 李国政; 刘小南; 徐宏明; 彭从斌

    2013-01-01

    AIM:To investigate the changes of neuroapoptosis in brain and learning ability after neonatal mice exposed to inhaled sevoflurane or isoflurane.METHODS:Ninety postnatal day(P)7 Wistar rats were randomly divided into 5 groups:group A sham anesthesia,group B 3.6% sevoflurane for 2 h,group C 3.6%sevoflurane for 6 h,group D 2.3% isoflurane for 2 h and group E 2.3% isoflurane for 6 h.Animals from each group were perfused transcardially with 0.1 mol phosphate buffer containing 4% paraformaldehyde 6 h after the end of anesthesia,and then the brains were exposed for immunohisochemistry,caspase-3 positive cells were detected.Behavioral studies with Morris water maze test were performed separately when the rats were 5-week-old and 14-week-old.RESULTS:The amounts of caspase-3 positive cells in the rats brain of Group B,C,D and E were greater than that in Group A,and the amount in group C was greater than that in gourp B,in group E more than that in group B(P<0.05).When face the spatial reference memory task or space exploration task,rats from different groups make it uniformly.Anesthetic rats and control rats performed similarly in terms of path length when learning to swim to the platform during locating trials.No rats showed significantly higher levels of retention during the probe trials in terms of target quadrant time,platform crossings and platform location time(P>0.05),but the number of platform crossings in group B,C,D and E was significantly higher than that in gourp A(P<0.05).CONCLUSION:Exposure to the concentration of 3.6% sevoflurane or 2.3 % isoflurane could cause brain cell apoptosis of newborn rats.Isoflurane could cause more insults to brain than sevoflurane at an equivalent concentration.The memory ability to pessimal stimulation is decreased as the anesthesia mice 5weeks old,such changes recede along with the growth of rats.Exposure to sevoflurane and isoflurane does not affect the spatial reference memory of newborn rat during their

  14. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  15. Sexual activity increases the number of newborn cells in the accessory olfactory bulb of male rats.

    Directory of Open Access Journals (Sweden)

    Wendy ePortillo

    2012-07-01

    Full Text Available In rodents, sexual behavior depends on the adequate detection of sexually relevant stimuli. The olfactory bulb (OB is a region of the adult mammalian brain undergoing constant cell renewal by continuous integration of new granular and periglomerular neurons in the accessory (AOB and main (MOB olfactory bulbs. The proliferation, migration, survival, maturation, and integration of these new cells to the OB depend on the stimulus that the subjects received. We have previously shown that 15 days after females control (paced the sexual interaction an increase in the number of cells is observed in the AOB. No changes are observed in the number of cells when females are not allowed to control the sexual interaction. In the present study we investigated if in male rats sexual behavior increases the number of new cells in the OB. Male rats were divided in five groups: 1 males that did not receive any sexual stimulation, 2 males that were exposed to female odors, 3 males that mated for 1 h and could not pace their sexual interaction, 4 males that paced their sexual interaction and ejaculated 1 time and 5 males that paced their sexual interaction and ejaculated 3 times. All males received three injections of the DNA synthesis marker bromodeoxyuridine at 1h intervals, starting 1h before the beginning of the behavioral test. Fifteen days later, males were sacrificed and the brains were processed to identify new cells and to evaluate if they differentiated into neurons. The number of newborn cells increased in the granular cell layer (also known as the internal cell layer of the AOB in males that ejaculated one or three times controlling (paced the rate of the sexual interaction. Some of these new cells were identified as neurons. In contrast, no significant differences were found in the mitral cell layer (also known as the external cell layer and glomerular cell layer of the AOB. In addition, no significant differences were found between groups in the MOB in

  16. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats

    Directory of Open Access Journals (Sweden)

    J. Yu

    Full Text Available The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry, and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1

  17. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats

    Science.gov (United States)

    Yu, J.; Luo, Y.; Yang, X.F.; Yang, M.X.; Yang, J.; Yang, X.S.; Zhou, J.; Gao, F.; He, L.T.; Xu, J.

    2016-01-01

    The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1β-positive cells

  18. Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung

    NARCIS (Netherlands)

    Kroon, A.A.; Wang, J.; Kavanagh, B.; Huang, Z.; Kuliszewski, M.; van Goudoever, J.B.; Post, M.

    2011-01-01

    The molecular mechanism(s) by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats.

  19. Fetal inflammatory response and brain injury in the preterm newborn.

    Science.gov (United States)

    Malaeb, Shadi; Dammann, Olaf

    2009-09-01

    Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

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

    Science.gov (United States)

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

    2013-11-01

    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 with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

  1. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  2. Feature Importance in Bayesian Assessment of Newborn Brain Maturity from EEG

    CERN Document Server

    Jakaite, L; Maple, C

    2010-01-01

    The methodology of Bayesian Model Averaging (BMA) is applied for assessment of newborn brain maturity from sleep EEG. In theory this methodology provides the most accurate assessments of uncertainty in decisions. However, the existing BMA techniques have been shown providing biased assessments in the absence of some prior information enabling to explore model parameter space in details within a reasonable time. The lack in details leads to disproportional sampling from the posterior distribution. In case of the EEG assessment of brain maturity, BMA results can be biased because of the absence of information about EEG feature importance. In this paper we explore how the posterior information about EEG features can be used in order to reduce a negative impact of disproportional sampling on BMA performance. We use EEG data recorded from sleeping newborns to test the efficiency of the proposed BMA technique.

  3. Devastating metabolic brain disorders of newborns and young infants.

    Science.gov (United States)

    Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

    2014-01-01

    Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis.

  4. Intraparenchymal brain hemorrhage and remote soft tissue arteriovenous malformation in a newborn infant.

    Science.gov (United States)

    Jee, Sandra H; Grow, Jennifer L; Faix, Roger G

    2002-12-01

    Congenital arteriovenous malformations (AVMs) often present with congestive heart failure. Such pathologic vascular structures typically occur in cranial, hepatic, or pulmonary locations and are usually associated with overlying external visible, tactile, or audible abnormalities. These vascular anomalies may also be associated with such complications as thromboembolic events, coagulopathy, and localized hemorrhage. We present a newborn infant with an occult but hemodynamically significant parascapular AVM who presented with an intraparenchymal brain hemorrhage, which we suspect to be a remote complication of the AVM.

  5. Language and the newborn brain: does prenatal language experience shape the neonate neural response to speech?

    Science.gov (United States)

    May, Lillian; Byers-Heinlein, Krista; Gervain, Judit; Werker, Janet F

    2011-01-01

    Previous research has shown that by the time of birth, the neonate brain responds specially to the native language when compared to acoustically similar non-language stimuli. In the current study, we use near-infrared spectroscopy to ask how prenatal language experience might shape the brain response to language in newborn infants. To do so, we examine the neural response of neonates when listening to familiar versus unfamiliar language, as well as to non language stimuli. Twenty monolingual English-exposed neonates aged 0-3 days were tested. Each infant heard low-pass filtered sentences of forward English (familiar language), forward Tagalog (unfamiliar language), and backward English and Tagalog (non-language). During exposure, neural activation was measured across 12 channels on each hemisphere. Our results indicate a bilateral effect of language familiarity on neonates' brain response to language. Differential brain activation was seen when neonates listened to forward Tagalog (unfamiliar language) as compared to other types of language stimuli. We interpret these results as evidence that the prenatal experience with the native language gained in utero influences how the newborn brain responds to language across brain regions sensitive to speech processing.

  6. Combined treatment of xenon and hypothermia in newborn rats--additive or synergistic effect?

    Directory of Open Access Journals (Sweden)

    Hemmen Sabir

    Full Text Available Breathing the inert gas Xenon (Xe enhances hypothermic (HT neuroprotection after hypoxia-ischemia (HI in small and large newborn animal models. The underlying mechanism of the enhancement is not yet fully understood, but the combined effect of Xe and HT could either be synergistic (larger than the two effects added or simply additive. A previously published study, using unilateral carotid ligation followed by hypoxia in seven day old (P7 rats, showed that the combination of mild HT (35°C and low Xe concentration (20%, both not being neuroprotective alone, had a synergistic effect and was neuroprotective when both were started with a 4 h delay after a moderate HI insult. To examine whether another laboratory could confirm this finding, we repeated key aspects of the study.After the HI-insult 120 pups were exposed to different post-insult treatments: three temperatures (normothermia (NT NT37°C, HT35°C, HT32°C or Xe concentrations (0%, 20% or 50% starting either immediately or with a 4 h delay. To assess the synergistic potency of Xe-HT, a second set (n = 101 of P7 pups were exposed to either HT35°C+Xe0%, NT+Xe20% or a combination of HT35°C+Xe20% starting with a 4 h delay after the insult. Brain damage was analyzed using relative hemispheric (ligated side/unligated side brain tissue area loss after seven day survival.Immediate HT32°C (p = 0.042, but not HT35°C significantly reduced brain injury compared to NT37°C. As previously shown, adding immediate Xe50% to HT32°C increased protection. Neither 4 h-delayed Xe20%, nor Xe50% at 37°C significantly reduced brain injury (p>0.050. In addition, neither 4 h-delayed HT35°C alone, nor HT35°C+Xe20% reduced brain injury. We found no synergistic effect of the combined treatments in this experimental model.Combining two treatments that individually were ineffective (delayed HT35°C and delayed Xe20% did not exert neuroprotection when combined, and therefore did not show a synergistic

  7. Odor-induced crawling locomotion in the newborn rat: Effects of amniotic fluid and milk.

    Science.gov (United States)

    Mendez-Gallardo, Valerie; Robinson, Scott R

    2014-04-01

    Early locomotion in the neonatal rat previously has been reported 3 days after birth during exposure to an odor of biological relevance (nest material). The current study explores if other ecologically relevant stimuli-amniotic fluid (AF) and milk-could evoke a similar locomotor response in the newborn rat and whether the endogenous opioid system mediates the response. Newborn rats tested 24 hr after birth were presented with the odors of AF or milk while placed in a runway. Pups expressed crawling and moved along the runway in response to direct exposure to the odors of AF and milk (Exp. 1). However, there was no evidence that this crawling response was altered after pretreatment with the opioid antagonist naloxone (Exp. 2). This study provides evidence of the capacity of AF and milk to evoke coordinated motor behavior, suggesting that they may play a role in the development of fundamental motor patterns.

  8. Towards the "baby connectome": mapping the structural connectivity of the newborn brain.

    Directory of Open Access Journals (Sweden)

    Olga Tymofiyeva

    Full Text Available Defining the structural and functional connectivity of the human brain (the human "connectome" is a basic challenge in neuroscience. Recently, techniques for noninvasively characterizing structural connectivity networks in the adult brain have been developed using diffusion and high-resolution anatomic MRI. The purpose of this study was to establish a framework for assessing structural connectivity in the newborn brain at any stage of development and to show how network properties can be derived in a clinical cohort of six-month old infants sustaining perinatal hypoxic ischemic encephalopathy (HIE. Two different anatomically unconstrained parcellation schemes were proposed and the resulting network metrics were correlated with neurological outcome at 6 months. Elimination and correction of unreliable data, automated parcellation of the cortical surface, and assembling the large-scale baby connectome allowed an unbiased study of the network properties of the newborn brain using graph theoretic analysis. In the application to infants with HIE, a trend to declining brain network integration and segregation was observed with increasing neuromotor deficit scores.

  9. 神经生长因子对新生大鼠缺氧/缺血性脑损伤远期智能的影响%The effect of long-term intelligence on NGF to the newborn rat with hypoxic-i schemic brain damage

    Institute of Scientific and Technical Information of China (English)

    王来栓; 朱长连; 程秀永; 王小阳; 杨静丽; 邱林; 朱洪; 周元聪

    2001-01-01

    Objective To investigate the effect of long-term intelligence on NGF to the newborn rats with hypoxic-ischemic brain damage (HI BD).Methods The model of newborn rat hypoxic-ischemic brain da mage(HIBD) was set,0.01mg/10g dosage NGF and 0.03mg/10g dosage NGF were administ ered to the rat abdominal cavity respectively. With maze-test, the change of le arning memory abilities of long-term in the rats were observed, the concentrat ion of monoamine neurotransmitters in the brain tissue were determined by high p erformance liquid chromatography electrochemical detector.Results The function of learning and memory was better in NGF group(small, large amou nt group)than in the control group, the frequency was lower remarkably than the control group(P<0.05),the correct rate was higher than the control group( P<0.05);there was remarkable difference in the above index between small dosage of NGF group and large dosage of NGF group(P<0.01);the content of m onoamine neurotransmitters especially NE, HVA and 5-HT was lower in NGF group t han in the control group(P<0.01).The formation of softening focus, calcific focus and colloid were seen, in the NGF group only mild atrophy of brain layer can be seen, there was no significant change in brain, but in the control group, there was cort ical atrophy, liquefaction and cavernous formation.Conclusion NGF could prevent and treat the intelligence defecit following HIBD, and might lighten the disorder of the monoamine neurotransmitters metabolism in HIBD and improved the recovery of its intelligence disorder.%目的 探讨神经生长因子(NGF)对新生大鼠缺氧/缺血性脑损伤(HIBD )后远期智能的影响.方法 建立新生大鼠缺氧/缺血性脑损伤模型, 分别给予NGF 0.01 mg/10 g(小剂量组)和0.03 mg/10 g(大剂量组)腹腔注射,采用迷宫实验观察大鼠远期学习记忆能力的改变,用高效液相色谱电化学法测定单胺类递质的改变. 结果  NGF组(小剂量组、大剂量组)学习

  10. Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yue Li; Huiying Gao

    2006-01-01

    BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily.OBJECTTVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult.DESTGN: Completely randomized grouping, controlled experiment.SETTING: Taian Health Center for Women and Children; Taishan Medical College.MATERTALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou.METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability(After test, 5 rats from each group were sacrificed and used for immunohistochemical staining) ② The right common carotid artery of newborn rats of model group was ligated under the sthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③Thalamencephal tissue

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

    Directory of Open Access Journals (Sweden)

    Dyuti Sharma

    2015-09-01

    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.

  12. A comparison of E15.5 fetus and newborn rat serum proteomes

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    Wei Lilong

    2012-11-01

    Full Text Available Abstract Background Serum proteins carry out several functions in the circulation, including transfer, immunological functions, messenger functions, coagulation, and regulation of homeostasis. To investigate changes in serum proteins that occur during development, the serum proteomes of embryonic 15.5 (E15.5 fetuses and newborn rats were compared using LC-MS/MS. Results A total of 958 proteins were identified in the serum of rats at both developmental stages. The serum proteome pattern of newborn rats was compared to E15.5 fetuses by relative quantitation. The expression patterns of hemoglobin subunits were different at the two stages, with most of the subunits having decreased expression in newborn rats compared to E15.5 fetuses. In addition, 8 of 12 apolipoproteins were significantly decreased and 10 of 11 identified complement molecules were increased, with 4 exhibiting a significant increase. Moreover, 11 of 14 of the significantly increased enzyme regulators were inhibitors. The serum proteome patterns of different littermates from both developmental stages were also compared. We found that the levels of many highly abundant serum proteins varied between littermates, and the variations were larger than the variations of the technical control. Conclusions The serum proteomes of newborn rats and E15.5 fetuses were compared. The expression patterns of hemoglobin subunits were different at the two developmental stages, with most of the subunits having decreased expression. The majority of apolipoproteins had significantly decreased expression, while almost all identified complement proteins had increased expression. The levels of several highly abundant serum proteins also varied among littermates at these two developmental stages. This is the first study using LC-MS/MS to investigate serum proteome development.

  13. Effect of manganese on heat stress protein synthesis of new-born rats

    Institute of Scientific and Technical Information of China (English)

    Ben-Yan Zhang; Sheng Chen; Fang-Li Ye; Chang-Cai Zhu; He-Xi Zhang; Rui-Bo Wang; Cheng-Fen Xiao; Tang-Chun Wu; Guo-Gao Zhang

    2002-01-01

    AIM: To study the effect of manganese (Mn) on heat stressprotein 70 (HSP70) synthesis in the brain and liver of new-bom rats whose mother-rats were exposed to Mn.METHODS: 32 female rats were randomly divided into fourgroups. One group was administrated with physiologicalsaline only as control group, the other three groups wereadministrated with 7.5, 15 and 30 mg@ kg-1 manganesechloride (MnCl2) by intraperitioneal injection every two daysfor two weeks. After delivery, the mother-rats receivedMnCl2 unceasingly for a week with the same method. Thenthe contents of Mn、 Zn、 Cu and Fe in the livers of the new-bom rats were determined by atomic absorptionspectroscopy; The level of HSP70 in the brains and thelivers of the new-born rats as detected by Westsrn-dot-blotting, and the SOD activities were measuredsimultaneously.RESULTS: The contents of Mn in the livers of new-bom ratsof the experimental groups(respective 1.38 ± 0.18, 2.73 ±0.65, 3.44 ± 0.89μg @ g-1) were significantly increasedcompared with the control group(0.88 ± 0.18μg@ g-1; p <0.01); The contents of Fe in the livers of new-bom rats of 15and 30 mg@ kg-1 experimental groups (426 ± 125,572 ± 175μg@g-1, respectively) were significantly increased comparedwith the control group(286±42μg@g-1; P<0.05); the levelsof Zn in the livers of the new-bom rats of three experimentalgroups( 254 ± 49, 263 ± 47, 213 ± 28μg@ g-1, respectively)were lower than those of the control group(335 ± 50μg@g-1;respective P<0.05, P<0.01); and the levels of Cu showedno significant difference among the four groups (threeexperimental groups: 75 ± 21, 68 ± 241 and 78 ± 18μg@g-1;control group: 83 ± 9μg@ g-1; p > 0.05). There was asignificant increase in the levels of HSP70 in the brains ofnew-bom rats of the 30 mg@kg-1 group (19.5 × 103 ± 1.3 ×103A; control group: 14.3 × 103 ± 1.4 × 103A; P< 0.01),andthe levels of HSP70 in the livers of new-bom rats of threeexperinental groups(respective 19.6 × 103

  14. Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Çagil Gökdogan

    2016-04-01

    Full Text Available ABSTRACT INTRODUCTION: Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD. OBJECTIVE: The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. METHODS: Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. RESULTS: In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67% and unilaterally in 2 rats (16.67% and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%. Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p < 0.05. CONCLUSION: Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder.

  15. Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia.

    Science.gov (United States)

    Gökdoğan, Çağıl; Genç, Aydan; Gülbahar, Özlem; Gökdoğan, Ozan; Helvacı, Ayşe; Bezgin, Selin Üstün; Memiş, Leyla

    2016-01-01

    Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD). The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67%) and unilaterally in 2 rats (16.67%) and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%). Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p<0.05). Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. No priming of the immune response in newborn Brown Norway rats dosed with ovalbumin in the mouth

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Pilegaard, Kirsten

    2003-01-01

    Background: Other researchers have reported that the specific immune response to subsequent antigen challenge is primed in newborn mice or rats dosed orally by gavage. We wanted to investigate if priming of a subsequent specific IgE response could be achieved by dosing newborn rats orally...... with ovalbumin in the mouth as neonates do not prime the specific immune response. The decrease in immune response found in our experiments when dosing newborn animals in the mouth in opposition to the priming seen by others when dosing by intra-gastric intubation may be explained by a dissimilar antigen...

  17. Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

    Science.gov (United States)

    Martínez-Orgado, José; Fernández-Frutos, Beatriz; González, Rita; Romero, Eva; Urigüen, Leire; Romero, Julián; Viveros, M Paz

    2003-06-10

    This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

  18. Successful xenotransplantation of microencapsulated newborn pig parathyroid cells in the treatment of hypoparathyroidism in rats

    Institute of Scientific and Technical Information of China (English)

    林乐岷; 宋一民; 宋纯; 许评; 宋春芳

    2003-01-01

    Objective To study the effect of xenotransplantation with pig parathyroid cells, which was prepared using cell microencapsulation technique, on the treatment of hypoparathyroidism in rats without immunosuppressor. Methods Parathyroid cells were isolated from 10 healthy newborn pigs and encapsulated in alginate-polylysine-alginate (APA) membranes. Thirty-two aparathyroid Wistar rats were randomly allocated to microcapsule, non-microcapsule, empty microcapsule, and control groups. Each rat was injected intraperitoneally with encapsulated porcine parathyroid cells, free porcine parathyroid cells, empty capsules or 0.9% NaCl, respectively. Total serum calcium and parathyroid hormone levels were monitored continuously for 40 weeks. And then, the transplant beds were retrieved and subjected to morphologic and electron microscopic examination. Results In those animals xenotransplanted with microencapsulated porcine parathyroid cells, the calcium and PTH levels were consistently within the normal range during the 40 weeks. In contrast, no therapeutic effects were observed in rats in the non-microcapsule group. Furthermore, neither empty capsules nor 0.9% NaCl were shown to have any effect on the recipient's serum calcium or PTH levels. After 40 weeks, electron microscopic examination demonstrated that the parathyroid cells within the microcapsules had survived well in vivo. Conclusions Xenotransplantation of microencapsulated newborn pig parathyroid cells can successfully treat hypoparathyroidism in rats without using immunosuppressive drugs. The results of this study show the possible clinical use of microencapsulated porcine parathyroid cells.

  19. Relationship between Notch Receptors and Hyperoxia-induced Lung Injury in Newborn Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate role of Notch1-3 in hyperoxia-induced lung injury in newborn rat exposed to 85% O2, SD rat litters born on the 22th day were randomly divided into two groups: room air group and hyperoxia group. The animals were sacrificed 1, 4, 7, 10, 14 and 21 days after continued exposure to oxygen (n=40, oxygen>0.85) or room air (n=40). 6 rats each group were used to assess lung histological changes by HE staining and expression of Notch in lungs by immunohistochemistry. Total RNA was extracted by Trizol reagent from frozen lung tissues. Notch mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that 7, 14 and 21 days after O2 exposure, hyperoxia group showed lung injury characterized by pulmonary edema, hemorrhage and lung development arrest. Positive staining for Notch1,Notch 2 in hyperoxia group was much lower than those in room air group at all time points (P<0.01, P<0.05), but compared with the controls, the hyperoxia group showed higher expression of Notch3 (P>0.05). Immunostained cells were typically airways epithelia, alveolar epithelial and inflammatory cells, and fibroblasts in hyperoxia group (P<0.01). Notch mRNA levels showed similar change as protein level (P< 0.01). It is concluded that the prolonged exposure to 85 % O2 resulted in abnormal expression of Notch receptors, which might contribute to the pathogenesis of hyperoxia-induced lung injury in newborn rats. The decreased inhibition of Notch1 might be one of the protective reaction and major mechanisms for proliferation/differentiation of type Ⅱ alveolar epithelial cells. The up-regulation of Notch3 activity might result in the lung development arrest of the newborn rats.

  20. Stereological evaluation of the volume and volume fraction of newborns' brain compartment and brain in magnetic resonance images.

    Science.gov (United States)

    Nisari, Mehtap; Ertekin, Tolga; Ozçelik, Ozlem; Cınar, Serife; Doğanay, Selim; Acer, Niyazi

    2012-11-01

    Brain development in early life is thought to be critical period in neurodevelopmental disorder. Knowledge relating to this period is currently quite limited. This study aimed to evaluate the volume relation of total brain (TB), cerebrum, cerebellum and bulbus+pons by the use of Archimedes' principle and stereological (point-counting) method and after that to compare these approaches with each other in newborns. This study was carried out on five newborn cadavers mean weighing 2.220 ± 1.056 g with no signs of neuropathology. The mean (±SD) age of the subjects was 39.7 (±1.5) weeks. The volume and volume fraction of the total brain, cerebrum, cerebellum and bulbus+pons were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods and by the use of fluid displacement technique. The mean (±SD) TB, cerebrum, cerebellum and bulbus+pons volumes by fluid displacement were 271.48 ± 78.3, 256.6 ± 71.8, 12.16 ± 6.1 and 2.72 ± 1.6 cm3, respectively. By the Cavalieri principle (point-counting) using sagittal MRIs, they were 262.01 ± 74.9, 248.11 ± 68.03, 11.68 ± 6.1 and 2.21 ± 1.13 cm3, respectively. The mean (± SD) volumes by point-counting technique using axial MR images were 288.06 ± 88.5, 275.2 ± 83.1, 19.75 ± 5.3 and 2.11 ± 0.7 cm3, respectively. There were no differences between the fluid displacement and point-counting (using axial and sagittal images) for all structures (p > 0.05). This study presents the basic data for studies relative to newborn's brain volume fractions according to two methods. Stereological (point-counting) estimation may be accepted a beneficial and new tool for neurological evaluation in vivo research of the brain. Based on these techniques we introduce here, the clinician may evaluate the growth of the brain in a more efficient and precise manner.

  1. Respiratory responses to progesterone and allopregnanolone following chronic caffeine treatment in newborn female rats.

    Science.gov (United States)

    Uppari, Naga Praveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    We recently showed that in 12-day-old male rats exposed to caffeine for 10 consecutive days, progesterone inhibits the respiratory response to hypoxia and increases apnea frequency (Uppari et al., 2016). This was partly due to a higher inhibitory response of GABAa receptor to allopregnanolone, the neuroactive metabolite of progesterone. In the present study, we addressed whether similar effects occur in females. We used newborn female rats daily gavaged with water (control) or caffeine (15mg/kg) between the postnatal (P) days 3-12. At P12, we recorded ventilation, metabolic rate, and apnea frequency and duration in normoxia and in response to moderate hypoxia, following an intraperitonial injection of progesterone (4mg/kg) or allopregnanolone (10mg/kg). In control rats, progesterone had no effect on breathing in normoxia and in hypoxia, and in rats treated with caffeine it decreased the initial increase in respiratory frequency in hypoxia. In both groups, allopregnalone decreased breathing frequency in normoxia and in hypoxia and increased the frequency of apnea in normoxia in control rats and in rats treated with caffeine. Injection of bicuculline (a specific GABAa receptor antagonist) prevented the inhibitory effects of allopregnanolone on breathing in both groups. These data indicate that chronic caffeine treatment unmasked an inhibitory effect of progesterone on the hypoxic response but this was weaker than in males, and contrasting to what was observed in male rats (Uppari et al., 2016), GABAa receptors are not significantly affected by chronic caffeine treatment in newborn female rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2.

    Science.gov (United States)

    Kirby, Elizabeth D; Muroy, Sandra E; Sun, Wayne G; Covarrubias, David; Leong, Megan J; Barchas, Laurel A; Kaufer, Daniela

    2013-04-16

    Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain. DOI:http://dx.doi.org/10.7554/eLife.00362.001.

  3. Repeated maternal dexamethasone treatments in late gestation increases 11beta-hydroxysteroid dehydrogenase type 1 expression in the hippocampus of the newborn rat.

    Science.gov (United States)

    Wan, Shunlun; Hao, Rusong; Sun, Kang

    This study was designed to investigate the effect of repeated maternal injections of dexamethasone in late gestation on the expression of newborn hippocampal 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), the enzyme amplifying glucocorticoids' action by converting biologically inactive 11-ketone metabolites into active glucocorticoids. Daily dexamethasone treatments (0.10 mg/kg body weight) in the last week of gestation were carried out in the pregnant rat. The expression of 11beta-HSD1 in the newborn hippocampal tissue was analyzed with Western blot and real-time polymerase chain reaction (PCR). The effect of corticosterone on the expression of 11beta-HSD1 was studied in cultured hippocampal neurons derived from newborn offspring received prenatal dexamethasone treatments. Both body and brain weights of the offspring were reduced significantly by repeated dexamethasone treatments in the last week of gestation. Western blot and real-time PCR analysis showed that both 11beta-HSD1 protein and mRNA expressions were increased significantly in the hippocampus of the newborn offspring on the first and seventh days after birth. Corticosterone could induce 11beta-HSD1 expression in cultured hippocampal neurons prepared from newborns received prenatal dexamethasone treatments, which was blocked by glucocorticoid receptor antagonist RU38486. The above findings suggest that repeated prenatal dexamethasone treatments at the end of gestation increase 11beta-HSD1 expression in the hippocampal tissue of the offspring, which may trigger a positive feedback pathway for the generation of biologically active glucocorticoids in the hippocampal tissue of the newborns.

  4. Labor Contractions Enhance Oxygenation and Behavioral Activity of Newborn Rat Pups

    Science.gov (United States)

    Mills, N. A.; Baer, L. A.; Ronca, A. E.; Balton, Bonnie (Technical Monitor)

    2002-01-01

    Labor contractions help instigate behavioral responses at birth (viz., breathing and suckling) that are vital for the newborn's adaptation to the extrauterine world (Ronca et al., 1996). In the present study, we analyzed the role of labor contractions in postpartum oxygenation and behavioral activity of newborn rat pups. Newborns were observed following either vaginal (V) or cesarean delivery. For cesarean delivery, day 21 pregnant dams' were administered a spinal transaction to eliminate lower body sensation, a laparotomy was performed and the uterus was maintained in a heated (37.5 C) bath. Four rat fetuses in one of the dams' paired uterine horn were compressed (C) to Simulate labor contractions (20 sec/min for 10 min) while four fetuses in the opposite horn were not compressed (NC). Fetuses were surgically removed from the uterus, stroked with a soft brush to mimic postnatal licking by the dam, the umbilical cord occluded. Pups were exposed to room temperature (22 C) for one hr, then nest temperature (33 C) for one hr. PO2, CO2, and O2, saturation were determined at 0, 30, 60, or 120 min post delivery using a blood gas analyzer. V and C delivered neonates showed comparable rates of PO2, CO2 and O2 saturation whereas NC neonates showed depressed levels at all time points (pcontractions in early postpartum adaptation.

  5. Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

    Science.gov (United States)

    Albert, Benjamin B; Vickers, Mark H; Gray, Clint; Reynolds, Clare M; Segovia, Stephanie A; Derraik, José G B; Lewandowski, Paul A; Garg, Manohar L; Cameron-Smith, David; Hofman, Paul L; Cutfield, Wayne S

    2016-09-01

    Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.

  6. Sensory feedback modulates quipazine-induced stepping behavior in the newborn rat.

    Science.gov (United States)

    Brumley, Michele R; Roberto, Megan E; Strain, Misty M

    2012-04-01

    Research has shown that sensory feedback modulates locomotor behavior in intact as well as spinal adult animals. Here we examined if locomotor activity ("stepping") in newborn rats is influenced by cutaneous and proprioceptive feedback. One-day-old rats were treated with the serotonergic receptor agonist quipazine (3.0mg/kg) to induce air-stepping behavior or with saline (vehicle control). During stepping, a substrate/floor (elastic, stiff, or none) was placed beneath their limbs so that the feet could make plantar surface contact with a substrate. Pups treated with quipazine showed significantly more alternated fore- and hindlimb steps and plantar paw contact with the substrate, compared to pups treated with saline. Pups also made proportionately less contact with the stiff substrate versus the elastic substrate during stepping. Different types of movements made on the substrate (paw pushes, taps, swipes, and stances) were also characterized. These results indicate that sensory feedback modulates locomotor mechanisms and behavior in perinatal rats.

  7. Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn

    Directory of Open Access Journals (Sweden)

    Mark Daniel WILSON

    2015-06-01

    Full Text Available How to Cite This Article: Wilson MD. Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn. Iran J Child Neurol. Spring2015; 9(2:9-16.AbstractObjectiveHypoxic insults are implicated in the spectrum of fetal disorders, including cerebral palsy (CP. In view of the major contribution of intrapartum risk factors and prematurity to subsequent neurological morbidity and mortality in humans, this study aimed to clarify the pathophysiology of brain injury, especially periventricular white matter damage (WMD, that occur in utero to the immature and near-term fetal CNS.Materials & MethodsAn evaluation of the resulting neurological and behavioural phenotype in the newborn was performed by utilising a battery of neurobehavioural tests, including the Morris water-maze and the open-field test, followed by cerebral MRI and histopathology.ResultsThis study used a murine model to examine the deleterious effects of WMD brought about by cerebral hypoxia-ischemia (HI and the characteristic features of CP in mice. Murine models have proven themselves valuable in the area of experimental neuroscience.Conclusion Hypoxia-treated mice were observed to demonstrate a significant neurofunctional deficit compared with sham mice on two behavioral measures. Indeed, different brain regions, including the sensorimotor cortex, the striatum, and the hippocampus were noticeably damaged after HI insult, as determined by both MRI and histopathology. These results, albeit qualitative in nature, appear to support the pre-existing finding that the long-term neurofunctional outcome in animal subjects with CP is strongly associated with the anatomical extent and pattern of cerebral damage as determined by both delayed neuroimaging and histopathology.

  8. Effect of Retinoic acid on Platelet-derived Growth Factor and Lung Development in Newborn Rats

    Institute of Scientific and Technical Information of China (English)

    陈红兵; 常立文; 刘汉楚; 容志惠; 祝华平; 张谦慎; 李文斌

    2004-01-01

    Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group.The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention, Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and pro tein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

  9. The Sex Differences of Morphology and Immunology of SIRS of Newborn Wistar Rats.

    Science.gov (United States)

    Kosyreva, A M

    2014-01-01

    The sex differences of infection and inflammatory diseases particularly appear at reproductive age and depend on the sex hormone level, varied between male and female. There are a few sets of data about the sex differences of infection and inflammatory diseases course, including systemic inflammatory response syndrome (SIRS) and sepsis, of newborns. The aim of our research was the estimation of morphological and immunological manifestation of SIRS of the newborn Wistar rats. Investigations were carried out on male and female two-day-old Wistar rats (10-12 g). SIRS was modeled by intraperitoneal injection of LPS (E. coli, O26: B6 strain, Sigma) in high dose-15 mg/kg. We did not find out any sex differences of the liver lesions severity between newborn males and females after LPS injection. The levels of endotoxin and estradiol in the serum, as the number of neutrophils in the intra-alveolar septa of the lungs, were higher in males than females with SIRS. Production of IL-2 and TNF-α by the spleen cells of males was higher than that in control group that reflects polarization predominantly on the Th1-type immune response. The secretion of IL-2, TNF-α, and IFN-γ by ConA activated spleen cells of females decreased that reflects the suppression of Th1-type immune response. We suppose that the LPS administration in the high dose causes the multidirectional reaction of the immune system of neonatal males and females Wistar rats.

  10. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, J; Liu, L; Chen, H

    2011-05-05

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (ptaurine was supplemented (ptaurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (ptaurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (ptaurine can significantly improve the IUGR fetal brain development.

  11. Bioavailability of cadmium from infant diets in newborn rats

    Energy Technology Data Exchange (ETDEWEB)

    Eklund, G.; Oskarsson, A. [Dept. of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala (Sweden); Petersson Grawe, K. [Toxicology Div., National Food Administration, Uppsala (Sweden)

    2001-11-01

    Infants are exposed to higher levels of cadmium (Cd) from infant and follow-on formulas than from breast milk. We studied the bioavailability of {sup 109}CdCl{sub 2} from cows' milk formula, soy formula, wheat/oat/milk formula, wholemeal/milk formula and water in 11-day-old rat pups. The pups received a single oral dose of one diet labelled with {sup 109}Cd, 0.1 or 0.3 mg Cd/kg body weight. After 2 or 24 h or 4, 9 or 12 days the fractional retention of {sup 109}Cd in the whole body, in segments of rinsed small intestine and in tissue was measured in a gamma counter. Pups receiving {sup 109}Cd in water or cows' milk formula had the highest mean whole-body retention. It ranged from 67% of the dose in the water group to 52% in the wholemeal/milk formula group 4 days after dosing. The retention of {sup 109}Cd in the rinsed small intestine was significantly higher in the water group and the cows' milk formula group than in the cereal-based formula groups at 24 h and 4 days after dosing. It was still high in all groups on day 9, ranging from 26 to 11%. Initially most of the {sup 109}Cd was retained in the duodenum but by day 4 it had moved further down into the jejunum. In the liver, the highest and lowest retention on day 4 was 16 permille and 3 permille of the dose in the water group and wholemeal/milk formula group, respectively. In the kidney, {sup 109}Cd was still increasing 12 days after exposure in all groups. Whole-body retention and tissue levels were higher than previously reported in adult animals. The lower bioavailability of {sup 109}Cd from the cereal-based formulas compared to water and cows' milk formula on the longer survival times is most likely explained by Cd binding to dietary fibre and phytic acid in the cereal-based formulas reducing the intestinal binding and decreasing the bioavailability of Cd. The high retention of {sup 109}Cd in the small intestine, leading to a prolonged absorption period, emphasizes the importance of

  12. Altered Functional Connectivity Following an Inflammatory White Matter Injury in the Newborn Rat: A High Spatial and Temporal Resolution Intrinsic Optical Imaging Study

    Directory of Open Access Journals (Sweden)

    Edgar Guevara

    2017-07-01

    Full Text Available Very preterm newborns have an increased risk of developing an inflammatory cerebral white matter injury that may lead to severe neuro-cognitive impairment. In this study we performed functional connectivity (fc analysis using resting-state optical imaging of intrinsic signals (rs-OIS to assess the impact of inflammation on resting-state networks (RSN in a pre-clinical model of perinatal inflammatory brain injury. Lipopolysaccharide (LPS or saline injections were administered in postnatal day (P3 rat pups and optical imaging of intrinsic signals were obtained 3 weeks later. (rs-OIS fc seed-based analysis including spatial extent were performed. A support vector machine (SVM was then used to classify rat pups in two categories using fc measures and an artificial neural network (ANN was implemented to predict lesion size from those same fc measures. A significant decrease in the spatial extent of fc statistical maps was observed in the injured group, across contrasts and seeds (*p = 0.0452 for HbO2 and **p = 0.0036 for HbR. Both machine learning techniques were applied successfully, yielding 92% accuracy in group classification and a significant correlation r = 0.9431 in fractional lesion volume prediction (**p = 0.0020. Our results suggest that fc is altered in the injured newborn brain, showing the long-standing effect of inflammation.

  13. Effectiveness of topical anesthetics on reducing tactile sensitivity in the paws of newborn rats.

    Science.gov (United States)

    Strain, Misty M; Vineyard, Mary Ann; Roberto, Megan E; Brumley, Michele R

    2014-01-01

    The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.5% prilocaine), alcaine (.5% proparacaine), triocaine (20% benzocaine, 6% lidocaine, and 4% tetracaine), or petroleum jelly (treatment control). Touch thresholds significantly increased after treatment with EMLA 18% of the time, and there was no evidence of a systemic effect. Touch thresholds were not significantly altered after treatment with alcaine, triocaine, or petroleum jelly. Therefore, EMLA appears to be a slightly effective topical anesthetic for reducing tactile sensitivity in newborn rats.

  14. Sensory feedback alters spontaneous limb movements in newborn rats: effects of unilateral forelimb weighting.

    Science.gov (United States)

    Brumley, Michele R; Robinson, Scott R

    2013-05-01

    Perinatal mammals show spontaneous movements that often appear random and uncoordinated. Here, we examined if spontaneous limb movements are responsive to a proprioceptive manipulation by applying a weight unilaterally to a forelimb of postnatal day 0 (P0; day of birth) and P1 rats. Weights were calibrated to approximate 0%, 25%, 50%, or 100% of the average mass of a forelimb, and were attached at the wrist. P0 and P1 pups showed different levels of activity during the period of limb weighting, in response to weight removal, and during the period after weighting. Pups exposed to 50% and 100% weights showed proportionately more activity in the nonweighted forelimb during the period of weighting, suggesting a threshold for evoking proprioceptive changes. Findings suggest that newborn rats use movement-related feedback to modulate spontaneous motor activity, and corroborate studies of human infants that have suggested a role for proprioception during early motor development.

  15. Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats.

    Science.gov (United States)

    Gargouri, M; Ben Saad, H; Ben Amara, I; Magné, C; El Feki, A

    2016-08-31

    Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.

  16. Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung.

    Directory of Open Access Journals (Sweden)

    Andreas A Kroon

    Full Text Available RATIONALE: The molecular mechanism(s by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. OBJECTIVE: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. METHODS: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg⁻¹. MEASUREMENT AND MAIN RESULTS: Ventilation for 24 h (h decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27(Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57(Kip2, decreased that of p16(INK4a, while the levels of p21(Waf/Cip1 and p15(INK4b were unchanged. Increased p27(Kip1 expression coincided with reduced phosphorylation of p27(Kip1 at Thr¹⁵⁷, Thr¹⁸⁷ and Thr¹⁹⁸ (p<0.05, thereby promoting its nuclear localization. Similar -but more rapid- changes in cell cycle regulators were noted when 7-day rats were ventilated with high tidal volume (40 mL.kg⁻¹ and when fetal lung epithelial cells were subjected to a continuous (17% elongation cyclic stretch. CONCLUSION: This is the first demonstration that prolonged (24 h of mechanical ventilation causes cell cycle arrest in newborn rat lungs; the arrest occurs in G₁ and is caused by increased expression and nuclear localization of Cdk inhibitor proteins (p27(Kip1, p57(Kip2 from the Kip family.

  17. Failure of the Nemo trial: bumetanide is a promising agent to treat many brain disorders but not newborn seizures

    Directory of Open Access Journals (Sweden)

    Yehezkel eBen-Ari

    2016-04-01

    Full Text Available The diuretic bumetanide failed to treat acute seizures due to hypoxic ischemic encephalopathy (HIE in newborn babies and was associated with hearing loss (NEMO trial; 1. On the other hand, clinical and experimental observations suggest that the diuretic might provide novel therapy for many brain disorders including autistic spectrum disorder, schizophrenia, Rett syndrome and Parkinson disease. Here, we discuss the differences between the pathophysiology of severe recurrent seizures in the neonates and neurological and psychiatric disorders stressing the uniqueness of severe seizures in newborn in comparison to other disorders.

  18. Failure of the Nemo Trial: Bumetanide Is a Promising Agent to Treat Many Brain Disorders but Not Newborn Seizures.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Damier, Philippe; Lemonnier, Eric

    2016-01-01

    The diuretic bumetanide failed to treat acute seizures due to hypoxic ischemic encephalopathy (HIE) in newborn babies and was associated with hearing loss (NEMO trial, Pressler et al., 2015). On the other hand, clinical and experimental observations suggest that the diuretic might provide novel therapy for many brain disorders including Autism Spectrum Disorders (ASD), schizophrenia, Rett syndrome, and Parkinson disease. Here, we discuss the differences between the pathophysiology of severe recurrent seizures in the neonates and neurological and psychiatric disorders stressing the uniqueness of severe seizures in newborn in comparison to other disorders.

  19. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  20. Neuroglobin in the rat brain: localization

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Allen, Gregg C; Nyengaard, Jens Randel

    2008-01-01

    in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation...

  1. {sup 26}Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, Sakae, E-mail: yumoto-s@viola.ocn.ne.j [Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, Tokyo (Japan); Kakimi, Shigeo [Faculty of Medicine, Nihon University, Tokyo (Japan); Matsuzaki, Hiroyuki [School of Engineering, The University of Tokyo, Tokyo (Japan)

    2010-04-15

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used {sup 26}Al as a tracer, and measured {sup 26}Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, {sup 26}AlCl{sub 3} was subcutaneously injected into pregnant rats. Considerable amounts of {sup 26}Al were measured in the tissues of newborn rats immediately after birth. The amounts of {sup 26}Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of {sup 26}Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  2. Aquaporin 9 in rat brain after severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2012-03-01

    Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

  3. CHANGES OF NITRIC OXIDE AND PROTECTIVE EFFECTS OF NITRIC OXIDE INHIBITORS IN NEWBORN RATS WITH SEPSIS

    Institute of Scientific and Technical Information of China (English)

    史源; 李华强; 潘捷; 沈际皋

    1995-01-01

    In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue or/and dexaraethason were investigated. The results revealed that plasma nitric oxide levels were ele-cted at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexam-etbasone was found to Munt hypoglycenua and hyperlacdcemla, to reduce the occurrence rate of loss ot re-sponse to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to de-crease the 24 h mortality. The results suggested that nitric coide play an important role during the course of fatal P. aeruginosa sepsis, hut it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.

  4. Effect of EGF on initiation of primordial follicle growth in ovary of newborn rat

    Institute of Scientific and Technical Information of China (English)

    柳海珍; 许复华; 刘以训

    2000-01-01

    The present study was designed to look at the effect of epidermal growth factor (EGF) and tomcie-stimulating hormone (FSH) on initiation of primordial follicle growth and differentiation in the ovary of newborn rat with a sensitive marker of proliferating cell nuclear antigen (PCNA). The results showed that more cuboidal granulosa cells (GC) were found in the ovary two days after injection of EGF. More proliferative GC were observed on D4. No such action of FSH on primordial follicles was demonstrated. Using in situ hybridization, inhibin a mRNA expression in GC was detected from D5, while FSH receptor (FSHR) mRNA expression started from D6 after birth. Both mRNAs increased following further development of the follicles. These results suggest that it is EGF, but not FSH, that may play a certain role in initiation of primordial follicle growth. FSH may be involved in further differentiation and growth of the early developmental follicles.

  5. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups.

    Science.gov (United States)

    Yazdani, Armin; Khoja, Zehra; Johnstone, Aaron; Dale, Laura; Rampakakis, Emmanouil; Wintermark, Pia

    2016-01-01

    Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

  6. [Rat brain cells containing ezrin (cytovillin)].

    Science.gov (United States)

    Korzhevskiĭ, D E; Kirik, O V; Giliarov, A V

    2011-01-01

    Ezrin (cytovillin or p81 protein) is an actin-binding protein, a member of ERM (ezrin, radixin and moesin) family, which species contribute to stabilization of the plasma membrane-formed structures. The aim of the present study was to demonstrate the ezrin-containing cells in the rat brain and to describe their topography and morphological features. The most pronounced immunohistochemical reaction to ezrin was found in the epithelium of the choroid plexus, cells of the subcommissural organ and ventricular ependyma. Moreover, ezrin staining was also detected in the unidentifiable cells in the subventricular zone, rostral migration pathway and astrocytes in various brain areas. Preferential ezrin localization in the brain cells contributing to formation of barrier structures suggests its involvement in transport processes in the CNS.

  7. The brains of very preterm newborns in clinically stable condition may be hyperoxygenated

    DEFF Research Database (Denmark)

    Sorensen, Line Caroe; Greisen, Gorm

    2009-01-01

    near-infrared spectroscopy in clinical steady state on the first day of life (median age: 19.2 hours). The mean gestational ages and birth weights in the 2 groups were 29.1 +/- 2.6 weeks versus 39.7 +/- 1.3 weeks and 1307 +/- 437 g versus 3484 +/- 346 g, respectively. Three preterm infants needed......OBJECTIVE: The objective was to compare cerebral oxygenation in preterm newborns with that in healthy term newborns. METHODS: Forty-six preterm newborns with gestational ages of weeks and 25 healthy term newborns were included. The cerebral tissue oxygenation index (c-TOI) was measured by using...... mechanical ventilation and 11 received inotropic drugs. Later, 3 preterm infants developed intraventricular hemorrhage and 2 infants died. All term infants were healthy newborns recruited in the maternity ward. RESULTS: There was a significant difference in c-TOI (preterm: 78.6% [95% confidence interval: 76.9%-80...

  8. Experimental modelling of the consequences of brief late gestation asphyxia on newborn lamb behaviour and brain structure.

    Directory of Open Access Journals (Sweden)

    Margie Castillo-Melendez

    Full Text Available Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient in utero asphyxia in late gestation fetal sheep, on the newborn lamb after birth. Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term, the cuff was inflated to induce umbilical cord occlusion (UCO, or sham (control. Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i use all four legs, (ii attain a standing position, (iii find the udder, and (iv successfully suckle--compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies.

  9. Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.

    Science.gov (United States)

    Mantovani, A; Macrì, C; Stazi, A V; Ricciardi, C; Guastadisegni, C; Maranghi, F

    1992-01-01

    Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.

  10. Protective Effects of Lycopene and Ellagic Acid on Gonadal Tissue, Maternal Newborn Rats Induced by Cadmiumchloride

    Directory of Open Access Journals (Sweden)

    K Hoshmand Motlagh

    2015-08-01

    Full Text Available Background & aim: Cadmium is a toxin which reduces the ability of the reproduction in humans .Different antioxidants damaging effects of toxins are eliminated .The purpose of this study was to investigate the protective effects of lycopene and Ellagic acid induced by cadmium chloride on the gonadal tissue of newborn rats during pregnancy. Methods: In the present experimental study, 30 adult female Wistar rats (180-200 gr were prepared and maintained in standard conditions. The female rats were used for mating with the male. After observation of vaginal plaque, pregnant rats were randomly divided into 5 groups of 6 rats. Group I (normal: They were given normal saline in 13 days during pregnancy. Group II (Control: Cadmium chloride (1.5 mg / kg/ IP was injected and normal saline was given to them in 13 days of during pregnancy. Group III: Cadmium chloride (1.5 mg / kg/ IP was injected and ellagic acid (10 mg/kg/orally in 13 days were injected during pregnancy. Group IV: Cadmium chloride (1.5 mg / kg/ IP was injected and copene acid (20 mg/kg/orally was injected in 13 days of during pregnancy. Group V: Cadmium chloride (1.5 mg / kg/ IP was injected and ellagic acid (10 mg/kg/orally and lycopene acid (20 mg/kg/orally were injected in 13 days during pregnancy. After postpartum, Neonatal rats were anesthetized with ether. Animals were dissected, then the testes and Ovaries were removed and transferred to 10% formalin solution. After tissue processing, tissue sections were prepared and H&E stained. Data were analyzed by SPSS software and ANOVA test. Results: Average number of Sertoli cells ,spermatogonia ,Leydig, and the number of seminiferous tube in control group were compared to other groups that were treated with lycopene - ellagic acid and ellagic acid had been reduced-proves to be significant(P <0.05. Average diameter of seminiferous tube in control group compared to other groups that are treated with lycopene - ellagic acid and ellagic acid had

  11. Postnatal Hyperoxia Exposure Differentially Affects Hepatocytes and Liver Haemopoietic Cells in Newborn Rats

    Science.gov (United States)

    Marconi, Guya Diletta; Zara, Susi; De Colli, Marianna; Di Valerio, Valentina; Rapino, Monica; Zaramella, Patrizia; Dedja, Arben; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

    2014-01-01

    Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized. PMID:25115881

  12. A study of the effects of pinealectomy on intestinal cell proliferation in infant newborn rats

    Directory of Open Access Journals (Sweden)

    Dalio Marcelo Belini

    2006-01-01

    Full Text Available PURPOSE: Study the proliferation rate of jejunum and large intestine crypt epithelial cells, in rats pinealectomized immediately after borning. METHODS: Twenty-four male Wistar rats were distributed into two groups: Acute group (n=12 and Chronic group (n=12. Six animals of each group were operated for removal of the pineal gland (pinealectomy-PnX, and other six were controls (sham pinealectomy-C. Animals from acute and chronic group were sacrificed 15 and 90 days after the surgery, respectively. RESULTS: In acute group, pinealectomy of new-born rats has not caused significant alteration in cell proliferation (PnX=58,77?1,77 and C=60,88?1,10 in the descending colon/ PnX=31,56?0,45 and C=31,73?0,47 in the proximal jejunum and in crypt cell population (PnX=24,92?4,82 and C=23,60?2,48 in the descending colon/ PnX=39,92?3,49 and C=44,32?5,56 in the proximal jejunum. However, in chronic group there was an uprising crypt cell production per crypt in the proximal jejunum (PnX=57,54?2,19 and C=47,19?7,3and in the descending colon (PnX=37,78?2,22 and C=17,92?2,28. CONCLUSION: As the increase of intestinal crypts epithelial cells in chronic group is a carcinogenesis predetermining factor, the understanding of the interaction between pineal gland and this event has great importance.

  13. Retrovirus-Mediated Gene Transfer in Immortalization of Progenitor Hair Cell Lines in Newborn Rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuan; ZHAI Suo-qiang; SONG Wei; GUO Wei; ZHENG Gui-liang; HU Yin-yan

    2008-01-01

    Objective To present an experimental method that allows isolation of greater epithelial ridge (GER) and lesser epithelial ridge(LER) cells from postnatal rat cochleae using a combinatorial approach of enzymatic digestion and mechanical separation and to investigate a retrovirus-mediated gene transfer technique for its possibl utility in immortalization of the GER and LER cell lines, in an effort to establish an in vitro model system of hair cell differentiation. Methods GER and LER cells were dissected from postnatal rat cochleae and immortalized by transferring the SV40 large T antigen using a retrovirus. The established cell lines were confirmed through morphology observation, immunnocytochemical staining and RT-PCR analysis. The Hathl gene was transferred into the cell lines using adenovirus-mediated techniques to explore their potential to differentiate into hair cells. Results The established cell lines were stably maintained for more than 20 passages and displayed many features similar to primary GER and LER cells. They grew in patches and assumed a polygonal morphology. Immunostaining showed labeling by SV40 large T antigen and Islet1 (a specific marker for GER and LER). All passages of the cell lines expressed SV40 large T antigen on RT-PCR analysis. The cells also showed the capability to differenti-ate into hair cell-like cells when forced to express Hathl. Conclusion Retrovirus-mediated gene transfer can be used in establishing immortalized progenitor hair cell lines in newborn rat, which may provide an invaluable system for studying hair cell differentiation and regeneration for new treatment of sensory hearing loss caused by hair cell loss.

  14. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......, and control of heart beat. Here we show that the rostral compact formation's ambiguus neurons, which control the esophageal phase of swallowing, display calcium-dependent plateau potentials in response to tetanic orthodromic stimulation or current injection. Whole cell recordings were made from visualized...... neurons in the rostral nucleus ambiguus using a slice preparation from the newborn mouse. Biocytin-labeling revealed dendritic trees with pronounced rostrocaudal orientations confined to the nucleus ambiguus, a morphological profile matching that of vagal motoneurons projecting to the esophagus. Single...

  15. Studies of aluminum in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  16. Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy

    Science.gov (United States)

    Fantini, Sergio; Hueber, Dennis; Franceschini, Maria Angela; Gratton, Enrico; Rosenfeld, Warren; Stubblefield, Phillip G.; Maulik, Dev; Stankovic, Miljan R.

    1999-06-01

    We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 µM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured

  17. [The expression of GFAP after brain concussion in rats].

    Science.gov (United States)

    Zhang, Chun-Bing; Li, Yong-Hong

    2006-04-01

    To study the expression of GFAP and pathologic changes after rats brain concussion, so that to provide evidence on brain concussion for forensic identification. Forty-five SD rats were divided into 3, 6, 12, 24 h and 2, 4, 7, 10 d and normal control groups in terms of different wounding time after brain concussion model established, and the expression of GFAP after rats brain concussion were then observed by using SP immunohistochemical method. In normal control brain, low-level GFAP expressions could be observed. After six hours' brain concussion, GFAP positive cells increased obviously. The trend reached to the peak at 7d, partly declined at 10d, then decreased gradually. Brain concussion induced the expression of GFAP. The detection of GFAP could be useful for diagnosis of brain concussion on forensic pathology, and could be a reference index for timing of injury after brain concussion.

  18. Brain perfusion monitoring with frequency-domain and continuous-wave near-infrared spectroscopy: a cross-correlation study in newborn piglets

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, G.; Katz, A.; Alfano, R.R. [Institute for Ultrafast Spectroscopy and Lasers and New York State Center for Advanced Technology for Ultrafast Photonic Materials and Applications Department of Electrical Engineering and Physics, The City College of the City University of New York, 138th Street and Convent Avenue, New York, NY 10031 (United States); Kofinas, A.D.; Kofinas, D.A.; Beyer, D. [Departments of Obstetrics and Gynecology and Medicine, The Brooklyn Hospital Center, The Affiliate of Weill Medical College of Cornell University, 121 De Kalb Avenue, Brooklyn, NY 11201 (United States); Stubblefield, P.G. [Department of Obstetrics and Gynecology, Boston University School of Medicine, 1 Boston Medical Center Place, Boston, MA 02118 (United States); Rosenfeld, W.; Maulik, D. [Departments of Obstetrics and Gynecology and Pediatrics, Winthrop University Hospital, State University of New York at Stony Brook, 251 First Street, Mineola, New York 11501 (United States); Stankovic, M.R. [Departments of Obstetrics and Gynecology and Medicine, The Brooklyn Hospital Center, The Affiliate of Weill Medical College of Cornell University, 121 De Kalb Avenue, Brooklyn, NY 11201 (United States); Department of Obstetrics and Gynecology, Boston University School of Medicine, 1 Boston Medical Center Place, Boston, MA 02118 (United States); Departments of Obstetrics and Gynecology and Pediatrics, Winthrop University Hospital, State University of New York at Stony Brook, 251 First Street, Mineola, New York 11501 (United States)

    2000-11-01

    The newborn piglet brain model was used to correlate continuous-wave (CW) and frequency-domain (FD) near-infrared spectroscopy. Six ventilated and instrumented newborn piglets were subjected to a series of manipulations in blood oxygenation with the effects on brain perfusion known to be associated with brain hypoxia-ischaemia. An excellent agreement between the CW and FD was demonstrated. This agreement improved when the scattering properties (determined by the FD device) were employed to calculate the differential pathlength factor, an important step in CW data processing. (author)

  19. Thalamic network oscillations synchronize ontogenetic columns in the newborn rat barrel cortex.

    Science.gov (United States)

    Yang, Jenq-Wei; An, Shuming; Sun, Jyh-Jang; Reyes-Puerta, Vicente; Kindler, Jennifer; Berger, Thomas; Kilb, Werner; Luhmann, Heiko J

    2013-06-01

    Neocortical areas are organized in columns, which form the basic structural and functional modules of intracortical information processing. Using voltage-sensitive dye imaging and simultaneous multi-channel extracellular recordings in the barrel cortex of newborn rats in vivo, we found that spontaneously occurring and whisker stimulation-induced gamma bursts followed by longer lasting spindle bursts were topographically organized in functional cortical columns already at the day of birth. Gamma bursts synchronized a cortical network of 300-400 µm in diameter and were coherent with gamma activity recorded simultaneously in the thalamic ventral posterior medial (VPM) nucleus. Cortical gamma bursts could be elicited by focal electrical stimulation of the VPM. Whisker stimulation-induced spindle and gamma bursts and the majority of spontaneously occurring events were profoundly reduced by the local inactivation of the VPM, indicating that the thalamus is important to generate these activity patterns. Furthermore, inactivation of the barrel cortex with lidocaine reduced the gamma activity in the thalamus, suggesting that a cortico-thalamic feedback loop modulates this early thalamic network activity.

  20. Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.

    Directory of Open Access Journals (Sweden)

    Maresha S Gay

    Full Text Available The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1, 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner.

  1. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    Directory of Open Access Journals (Sweden)

    Thông Hua-Huy

    2016-02-01

    Full Text Available Inhaled nitric oxide (iNO is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group or 20 ppm (iNO-20 ppm group, or in room air (control group. Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  2. Postnatal leptin is necessary for maturation of numerous organs in newborn rats.

    Science.gov (United States)

    Attig, Linda; Larcher, Thibaut; Gertler, Arieh; Abdennebi-Najar, Latifa; Djiane, Jean

    2011-01-01

    The postnatal leptin surge, described particularly in rodents, has been demonstrated to be crucial for hypothalamic maturation and brain development. In the present study, the possible general effects of this hormone on maturation of numerous peripheral organs have been explored. To test this hypothesis, we used a leptin antagonist (L39A/D40A/F41A) to investigate the effects of the blockage of postnatal leptin action on neonatal growth and maturation of organs involved in metabolism regulation, reproduction and immunity. For that purpose, newborn female pups were subcutaneously injected from days 2-13 with either saline or leptin antagonist and sacrificed at weaning. Organs were submitted to histological and immunohistochemical analyses. Leptin antagonist treatment clearly impaired the maturation of pancreas, kidney, thymus and ovary. All these alterations, at the organ level, occurred without changes in the whole-body mass of the animals. Leptin antagonist treatment induced: (1) a reduction in b cell area and a concomitant increase of a cells in Langherans islets in the pancreas, (2) a reduction in the number of glomeruli and a persistence of immature glomeruli in kidney, (3) an increase in the thymic cortical layer thickness, reflecting an unmatured stage, (4) a drastic reduction of the pool of primordial follicles, in ovaries. All these results strongly argue for a crucial role of leptin for the achievement of organ maturation, opening new perspectives in the field of leptin physiology and organ development.

  3. Regulation of oxidative stress and somatostatin, cholecystokinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats.

    Science.gov (United States)

    Coskun, Zeynep Mine; Sacan, Ozlem; Karatug, Ayse; Turk, Neslihan; Yanardag, Refiye; Bolkent, Sehnaz; Bolkent, Sema

    2013-09-01

    The aim of the study was to determine whether ghrelin treatment has a protective effect on gene expression and biochemical changes in the stomach of newborn streptozotocin (STZ) induced diabetic rats. In this study, four groups of Wistar rats were used: control, ghrelin control, diabetic and diabetic+ghrelin. The rats were sacrificed after four weeks of treatment for diabetes. The gene expressions of: somatostatin, cholecystokinin, apelin and the altered active caspase-3, active caspase-8, proliferating cell nuclear antigen, were investigated in the pyloric region of the stomach and antioxidant parameters were measured in all the stomach. Although ghrelin treatment to diabetic rats lowered the stomach lipid peroxidation levels, the stomach glutathione levels were increased. Exogenous ghrelin caused an increased activities of stomach catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase in diabetic rats. Numbers of somatostatin, cholecystokinin and proliferating cell nuclear antigen immunoreactive cells decreased in the diabetic+ghrelin group compared to the diabetic group. Apelin mRNA expressions were remarkably less in the diabetic+ghrelin rats than in diabetic rats. The results may indicate that ghrelin treatment has a protective effect to some extent on the diabetic rats. This protection is possibly accomplished through the antioxidant activity of ghrelin observed in type 2 diabetes. Consequently exogenous ghrelin may be a candidate for therapeutic treatment of diabetes. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Near-Infrared Image Reconstruction of Newborns' Brains: Robustness to Perturbations of the Source/Detector Location.

    Science.gov (United States)

    Ahnen, L; Wolf, M; Hagmann, C; Sanchez, S

    2016-01-01

    The brain of preterm infants is the most vulnerable organ and can be severely injured by cerebral ischemia. We are working on a near-infrared imager to early detect cerebral ischemia. During imaging of the brain, movements of the newborn infants are inevitable and the near-infrared sensor has to be able to function on irregular geometries. Our aim is to determine the robustness of the near-infrared image reconstruction to small variations of the source and detector locations. In analytical and numerical simulations, the error estimations for a homogeneous medium agree well. The worst case estimates of errors in reduced scattering and absorption coefficient for distances of r=40 mm are acceptable for a single source-detector pair. The optical properties of an inhomogeneity representing an ischemia are reconstructed correctly within a homogeneous medium, if the error in placement is random.

  5. Extra corporeal membrane oxygenation in newborns : implications for brain and lung

    NARCIS (Netherlands)

    Heijst, Adrianus Franciscus Jacobus van

    2004-01-01

    Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for newborns with severe respiratory insufficiency. In veno-arterial ECMO, venous blood is drained from the right atrium, oxygenated in an artificial lung and reinfused in the aorta. For vascular access the right internal jugular vein

  6. Biochemical studies of mouse brain tubulin: colchicine binding (DEAE-cellulose filter) assay and subunits ( α and β) biosynthesis and degradation (in newborn brain)

    Energy Technology Data Exchange (ETDEWEB)

    Tse, Cek-Fyne [Univ. of Rochester, NY (United States)

    1978-01-01

    A DEAE-cellulose filter assay, measuring (3H)colchicine bound to colchicine binding protein (CBP) absorbed on filter discs, has been modified to include lM sucrose in the incubation medium for complexing colchicine to CBP in samples before applying the samples to filter discs (single point assay). Due to the much greater stability of colchicine binding capacity in the presence of lM sucrose, multiple time-point assays and least squares linear regression analysis were not necessary for accurate determination of CBP in hybrid mouse brain at different stages of development. The highest concentrations of CBP were observed in the 160,000g supernatant and pellet of newborn brain homogenate. Further studies of the modified filter assay documented that the assay has an overall counting efficiency of 27.3%, that DEAE-cellulose filters bind and retain all tubulin in the assay samples, and that one molecule of colchicine binds approximately one molecule of tubulin dimer. Therefore, millimoles of colchicine bound per milligram total protein can be used to calculate tubulin content. With this technique tubulin content of brain supernatant was found to be 11.9% for newborn, and 7.15% for 11 month old mice. Quantitative densitometry was also used to measure mouse brain supernatant actin content for these two stages. In vivo synthesis and degradation rates of tubulin ..cap alpha.. and ..beta.. subunits of two day mouse brain 100,000g supernatant were studied after intracerebral injection of (3H)leucine. Quantitative changes of the ratio of tritium specific activities of tubulin ..cap alpha.. and ..beta.. subunits with time were determined. The pattern of change was biphasic. During the first phase the ratio decreased; during the second phase the ratio increased continuously. An interpretation consistent with all the data in this study is that the ..cap alpha.. subunit is synthesized at a more rapid rate than the ..beta.. subunit. (ERB)

  7. Maternal consumption of trans-fatty acids during the first half of gestation are metabolically available to suckled newborn rats.

    Science.gov (United States)

    Amusquivar, Encarnacíón; Sánchez-Blanco, Clara; Clayton, Jaime; Cammarata, Giulia; Herrera, Emilio

    2014-03-01

    Dietary trans-fatty acids (t-FA) during pregnancy have adverse effects on growth and development. To determine the effect of dietary t-FA during just the first half of pregnancy, rats were given a diet containing 8 % hydrogenated peanut oil and 2 % olive oil (PO) and compared to rats given a diet containing 10 % olive oil (OO). After 12 days all rats were fed standard diet and were studied at days 12 or 20 of pregnancy or days 1 or 6 postpartum. At day 12 of pregnancy there were small differences in the plasma and lumbar adipose tissue fatty acid profiles and elaidic acid [18:1(n-9)t] was present in the PO group. From day 12 to 20 of pregnancy, plasma non-esterified fatty acids, glycerol, triacylglycerols (TAG) and most individual fatty acids increased more in PO than in OO. At day 20 of pregnancy in the PO group most plasma elaidic acid appeared as plasma TAG and was also present in the mammary gland, to decline in both sites at day 1 postpartum. Elaidic acid concentration was low in the plasma of 20-day fetuses, increased in 1-day newborns declining at day 6. Thus t-FA, eaten during early pregnancy, accumulated in maternal adipose tissue and were released during late pregnancy to be taken up by the mammary gland becoming available to the newborns during suckling.

  8. Cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets.

    Directory of Open Access Journals (Sweden)

    Richdeep S Gill

    Full Text Available Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H(2O(2 production and markers of oxidative stress. Piglets (1-4 d, 1.4-2.5 kg were block-randomized into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation (n = 8/group. At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls or cyclosporine (2.5 or 10 mg/kg i.v. bolus in a blinded-randomized fashion. An additional sham-operated group (n = 4 underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe, cerebral cortical H(2O(2 production (electrochemical sensor, cerebral tissue glutathione (ELISA and cytosolic cytochrome-c (western blot levels were examined. Hypoxic piglets had cardiogenic shock (cardiac output 40-48% of baseline, hypotension (mean arterial pressure 27-31 mmHg and acidosis (pH 7.04 at the end of 2 h of hypoxia. Post-resuscitation cyclosporine treatment, particularly the higher dose (10 mg/kg, significantly attenuated the increase in cortical H(2O(2 concentration during reoxygenation, and was associated with lower cerebral oxidized glutathione levels. Furthermore, cyclosporine treatment significantly attenuated the increase in cortical cytochrome-c and lactate levels. Carotid blood arterial flow was similar among groups during reoxygenation. Conclusively, post-resuscitation administration of cyclosporine significantly attenuates H(2O(2 production and minimizes oxidative stress in newborn piglets following hypoxia-reoxygenation.

  9. Brain Cooling With Ventilation of Cold Air Over Respiratory Tract in Newborn Piglets: An Experimental and Numerical Study.

    Science.gov (United States)

    Bakhsheshi, Mohammad Fazel; Moradi, Hadi Vafadar; Stewart, Errol E; Keenliside, Lynn; Lee, Ting-Yim

    2015-01-01

    We investigate thermal effects of pulmonary cooling which was induced by cold air through an endotracheal tube via a ventilator on newborn piglets. A mathematical model was initially employed to compare the thermal impact of two different gas mixtures, O2-medical air (1:2) and O2-Xe (1:2), across the respiratory tract and within the brain. Following mathematical simulations, we examined the theoretical predictions with O2-medical air condition on nine anesthetized piglets which were randomized to two treatment groups: 1) control group ([Formula: see text]) and 2) pulmonary cooling group ([Formula: see text]). Numerical and experimental results using O2-medical air mixture show that brain temperature fell from 38.5 °C and 38.3 °C ± 0.3 °C to 35.7 °C ± 0.9 °C and 36.5 °C ± 0.6 °C during 3 h cooling which corresponded to a mean cooling rate of 0.9 °C/h ± 0.2 °C/h and 0.6 °C/h ± 0.1 °C/h, respectively. According to the numerical results, decreasing the metabolic rate and increasing air velocity are helpful to maximize the cooling effect. We demonstrated that pulmonary cooling by cooling of inhalation gases immediately before they enter the trachea can slowly reduce brain and core body temperature of newborn piglets. Numerical simulations show no significant differences between two different inhaled conditions, i.e., O2-medical air (1:2) and O2-Xe (1:2) with respect to cooling rate.

  10. Cyclosporine Treatment Reduces Oxygen Free Radical Generation and Oxidative Stress in the Brain of Hypoxia-Reoxygenated Newborn Piglets

    Science.gov (United States)

    Liu, Jiang-Qin; Chaudhary, Hetal; Brocks, Dion R.; Bigam, David L.; Cheung, Po-Yin

    2012-01-01

    Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H2O2) production and markers of oxidative stress. Piglets (1–4 d, 1.4–2.5 kg) were block-randomized into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation)(n = 8/group). At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls) or cyclosporine (2.5 or 10 mg/kg i.v. bolus) in a blinded-randomized fashion. An additional sham-operated group (n = 4) underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H2O2 production (electrochemical sensor), cerebral tissue glutathione (ELISA) and cytosolic cytochrome-c (western blot) levels were examined. Hypoxic piglets had cardiogenic shock (cardiac output 40–48% of baseline), hypotension (mean arterial pressure 27–31 mmHg) and acidosis (pH 7.04) at the end of 2 h of hypoxia. Post-resuscitation cyclosporine treatment, particularly the higher dose (10 mg/kg), significantly attenuated the increase in cortical H2O2 concentration during reoxygenation, and was associated with lower cerebral oxidized glutathione levels. Furthermore, cyclosporine treatment significantly attenuated the increase in cortical cytochrome-c and lactate levels. Carotid blood arterial flow was similar among groups during reoxygenation. Conclusively, post-resuscitation administration of cyclosporine significantly attenuates H2O2 production and minimizes oxidative stress in newborn piglets following hypoxia

  11. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke

    National Research Council Canada - National Science Library

    Zhang, Qiu-Wan; Deng, Xu-Xu; Sun, Xiao; Xu, Jin-Xiu; Sun, Feng-Yan

    2013-01-01

    Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO) can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function...

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

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

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

  13. Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Dezhi Kang; Zhang Guo

    2008-01-01

    BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats

  14. Ultrastructural features of the myotendinous junction of the sternomastoid muscle in Wistar rats: from newborn to aging.

    Science.gov (United States)

    Polican Ciena, Adriano; Yokomizo De Almeida, Sonia Regina; De Sousa Bolina, Cristina; De Sousa Bolina-Matos, Regina; Grassi Rici, Rose Eli; Pereira Da Silva, Marcelo Cavenaghi; Miglino, Maria Angélica; Watanabe, Ii-sei

    2012-09-01

    The myotendinous junction (MTJ) is a major area for transmitting force from the skeletal muscle system and acts in joint position and stabilization. This study aimed to use transmission electron microscopy to describe the ultrastructural features of the MTJ of the sternomastoid muscle in Wistar rats from newborn to formation during adulthood and possible changes with aging. Ultrastructural features of the MTJ from the newborn group revealed pattern during development with interactions between muscle cells and extracellular matrix elements with thin folds in the sarcolemma and high cellular activity evidenced through numerous oval mitochondria groupings. The adult group had classical morphological features of the MTJ, with folds in the sarcolemma forming long projections called "finger-like processes" and sarcoplasmic invaginations. Sarcomeres were aligned in series, showing mitochondria near the Z line in groupings between collagen fiber bundles. The old group had altered "finger-like processes," thickened in both levels of sarcoplasmic invaginations and in central connections with the lateral junctions. We conclude that the MTJ undergoes intense activity from newborn to its formation during adulthood. With increasing age, changes to the MTJ were observed in the shapes of the invaginations and "finger-like processes" due to hypoactivity, potentially compromising force transmission and joint stability. Copyright © 2012 Wiley Periodicals, Inc.

  15. 26Al uptake and accumulation in the rat brain

    Science.gov (United States)

    Yumoto, S.; Nagai, H.; Imamura, M.; Matsuzaki, H.; Hayashi, K.; Masuda, A.; Kumazawa, H.; Ohashi, H.; Kobayashi, K.

    1997-03-01

    To investigate the cause of Alzheimer's disease (senile dementia), 26Al incorporation in the rat brain was studied by accelerator mass spectrometry (AMS). When 26Al was injected into healthy rats, a considerable amount of 26Al entered the brain (cerebrum) through the blood-brain barrier 5 days after a single injection, and the brain 26Al level remained almost constant from 5 to 270 days. On the other hand, the level of 26Al in the blood decreased remarkably 75 days after injection. Approximately 89% of the 26Al taken in by the brain cell nuclei bound to chromatin. This study supports the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium (Al) in the brain, and brain cell nuclei.

  16. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    JTEkanem

    effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ... SOD is an important enzyme family in living cells for maintaining ..... one unit of activity with oxidation rate of organic substrate in.

  17. Further characterization of the process of in vitro uptake of radiolabeled copper by the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Barnea, A.; Hartter, D.E.; Cho, G.; Bhasker, K.R.; Katz, B.M.; Edwards, M.D. (Univ. of Texas, Dallas (USA))

    1990-10-01

    We have previously demonstrated that hypothalmic slices obtained from adult male rats accumulate {sup 67}Cu by two ligand-dependent, saturable processes: a high and low affinity process. To further establish the generality of these uptake processes, we defined the ligand requirements and the saturation kinetics of {sup 67}Cu uptake by tissue slices obtained from the newborn hypothalamus (HT); adult male hypothalamus, hippocampus, cortex, median eminence, and caudate nucleus; hypothalamus and hippocampus of castrated (14 days) males and of pregnant (19 days) and ovariectomized (14 days) females. It was found that ionic {sup 67}Cu{sup 2}{sup +} was poorly taken up by newborn HT and adult caudate, complexation with His enhanced {sup 67}Cu uptake 3-4-fold, and complexation with albumin inhibited {sup 67}Cu uptake. These ligand requirements are identical to those we have previously shown for the adult HT. When {sup 67}Cu uptake was evaluated under conditions optimal for the high or the low affinity process, for each process the dose response curves generated from these various tissues were very similar. In addition, we assessed the uptake of both components of the CuHis2 complex by incubating tissues with {sup 67}Cu{sup 3 H}-His2 and found that the tissue ratio of {sup 67}Cu:{sup 3}H was a sigmoidal function of the concentration of the Cu complex such that at greater than 5 microM, the ratio was about 3-fold greater than the medium ratio; indicating preferential uptake of {sup 67}Cu relative to {sup 3}H-His. The changes in isotope ratios were observed in newborn HT and adult HT, as well as caudate. These similarities in the ligand requirements and saturation kinetics of {sup 67}Cu uptake establish the generality of these two processes of in vitro uptake of copper in the rat brain.

  18. Immunocytochemical study of amelogenin deposition during the early odontogenesis of molars in alendronate-treated newborn rats.

    Science.gov (United States)

    Massa, Luciana F; Bradaschia-Correa, Vivian; Arana-Chavez, Victor E

    2006-06-01

    Newborn rats were treated with sodium alendronate to study how enamel is formed and the effect of alendronate during early odontogenesis. Ultrastructural analysis combined with high-resolution immunocytochemistry for amelogenin was carried out. Twelve rats were subjected to daily SC injections of sodium alendronate (2.5 mg/kg/day) for 3 days on their dorsal region, whereas three rats were daily injected with saline solution as a control. Molar tooth germs from 3-day-old rats were fixed under microwave irradiation in 0.1% glutaraldehyde + 4% formaldehyde buffered at pH 7.2 with 0.1 M sodium cacodylate. The specimens were left undecalcified, postfixed with osmium tetroxide, dehydrated, and embedded in LR White resin. Ultrathin sections were incubated with a chicken anti-24-kDa rat amelogenin antibody, a secondary antibody, and finally with a protein A-gold complex. Large patches of amelogenin were present over the unmineralized mantle dentin and at early secretory ameloblasts. At more advanced stages, they were also detected at the enamel matrix, as well as in the mineralized dentin, at the periodontoblastic space of the dentinal tubules, and at the predentin. It is likely that the main effect of alendronate at early stages of odontogenesis is the increase of synthesis/secretion of amelogenin, promoting its deposition within the forming dentin and enamel.

  19. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  20. Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups.

    Directory of Open Access Journals (Sweden)

    Winfried Neuhaus

    Full Text Available Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl-D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4. Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation.

  1. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    Energy Technology Data Exchange (ETDEWEB)

    Ancora, G. [Neonatal Intensive Care Unit, Department of Mother and Infant Infermi Hospital of Rimini, Rimini (Italy); Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R. [Department of Biomedical and Neuromotor Sciences University of Bologna, MR Functional Unit, Bologna (Italy); Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G. [University of Bologna, Neonatology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Tani, G. [University of Bologna, Radiology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Malucelli, E. [University of Bologna, Department of Pharmacy and Biotechnologies, Bologna (Italy)

    2013-08-15

    MRI, proton magnetic resonance spectroscopy ({sup 1}H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on {sup 1}H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and {sup 1}H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both {sup 1}H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of {sup 1}H-MRS and DTI, which outperform conventional MRI. (orig.)

  2. Waxholm Space atlas of the Sprague Dawley rat brain

    OpenAIRE

    Papp, Eszter A.; Trygve B. Leergaard; Calabrese, Evan; Johnson, G. Allan; Bjaalie, Jan G.

    2014-01-01

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in ...

  3. Actin purification from a gel of rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Peron-Renner, M; Coffe, G; Pudles, J

    1984-01-01

    Actin, 99% pure, has been recovered from rat brain with a high yield (greater than 15 mg/100 g brain). We have shown that: 1. a low ionic strength extract from rat brain tissue is capable of giving rise to a gel; 2. actin is the main gel component and its proportion is one order of magnitude higher than in the original extract; 3. actin can be isolated from this extract by a three-step procedure involving gelation, dissociation of the gel in 0.6 M KCl, followed by one or two depolymerization-polymerization cycles.

  4. Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

    Science.gov (United States)

    Yang, Dianer; Sun, Yu-Yo; Bhaumik, Siddhartha Kumar; Li, Yikun; Baumann, Jessica M; Lin, Xiaoyi; Zhang, Yujin; Lin, Shang-Hsuan; Dunn, R Scott; Liu, Chia-Yang; Shie, Feng-Shiun; Lee, Yi-Hsuan; Wills-Karp, Marsha; Chougnet, Claire A; Kallapur, Suhas G; Lewkowich, Ian P; Lindquist, Diana M; Murali-Krishna, Kaja; Kuan, Chia-Yi

    2014-12-03

    Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.

  5. Hemispheric Asymmetries in Repetition Enhancement and Suppression Effects in the Newborn Brain.

    Directory of Open Access Journals (Sweden)

    Camillia Bouchon

    Full Text Available The repeated presentation of stimuli typically attenuates neural responses (repetition suppression or, less commonly, increases them (repetition enhancement when stimuli are highly complex, degraded or presented under noisy conditions. In adult functional neuroimaging research, these repetition effects are considered as neural correlates of habituation. The development and respective functional significance of these effects in infancy remain largely unknown.This study investigates repetition effects in newborns using functional near-infrared spectroscopy, and specifically the role of stimulus complexity in evoking a repetition enhancement vs. a repetition suppression response, following up on Gervain et al. (2008. In that study, abstract rule-learning was found at birth in cortical areas specific to speech processing, as evidenced by a left-lateralized repetition enhancement of the hemodynamic response to highly variable speech sequences conforming to a repetition-based ABB artificial grammar, but not to a random ABC grammar.Here, the same paradigm was used to investigate how simpler stimuli (12 different sequences per condition as opposed to 140, and simpler presentation conditions (blocked rather than interleaved would influence repetition effects at birth.Results revealed that the two grammars elicited different dynamics in the two hemispheres. In left fronto-temporal areas, we reproduce the early perceptual discrimination of the two grammars, with ABB giving rise to a greater response at the beginning of the experiment than ABC. In addition, the ABC grammar evoked a repetition enhancement effect over time, whereas a stable response was found for the ABB grammar. Right fronto-temporal areas showed neither initial discrimination, nor change over time to either pattern.Taken together with Gervain et al. (2008, this is the first evidence that manipulating methodological factors influences the presence or absence of neural repetition enhancement

  6. Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; Fekete, Saskia; Zhu, Anli; Frank, Melissa

    2010-09-01

    Neural stem/progenitor cell (NSP) biology and neurogenesis in adult central nervous system (CNS) are important both towards potential future therapeutic applications for CNS repair, and for the fundamental function of the CNS. In the present study, we report the characterization of NSP population from subventricular zone (SVZ) of neonatal piglet brain using in vivo and in vitro systems. We show that the nestin and vimentin-positive neural progenitor cells are present in the SVZ of the lateral ventricles of neonatal piglet brain. In vitro, piglet NSPs proliferated as neurospheres, expressed the typical protein of neural progenitors, nestin and a range of well-established neurodevelopmental markers. Upon dissociation and subculture, piglet NSPs differentiated into neurons and glial cells. Clonal analysis demonstrates that piglet NSPs are multipotent and retain the capacity to generate both glia and neurons. These cells expressed VEGF, VEGFR1, VEGFR2 and Neuropilin-1 and -2 mRNAs. Real time PCR revealed that SVZ NSPs from newborn piglet expressed total VEGF and all VEGF splice variants. These findings show that piglet NSPs may be helpful to more effectively design growth factor based strategies to enhance endogenous precursor cells for cell transplantation studies potentially leading to the application of this strategy in the nervous system disease and injury.

  7. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  8. Effect of propofol in the immature rat brain on short- and long-term neurodevelopmental outcome.

    Directory of Open Access Journals (Sweden)

    Tanja Karen

    Full Text Available BACKGROUND: Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment. METHODS: 6-day-old Wistar rats (P6, randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120. RESULTS: Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3 in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point. CONCLUSION: Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.

  9. Non-signalling energy use in the developing rat brain.

    Science.gov (United States)

    Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N; Attwell, David

    2017-03-01

    Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.

  10. EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA

    Directory of Open Access Journals (Sweden)

    Hector Lafuente

    2016-07-01

    Full Text Available Background: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.Methods: Hypoxic-ischemic animals were randomized to receive 30 min after the insult: 1 normothermia- and vehicle-treated group; 2 normothermia- and cannabidiol-treated group; 3 hypothermia- and vehicle-treated group; and 4 hypothermia- and cannabidiol-treated group. Six hours after treatment, brains were processed to qualify the number of neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate and excitotoxicity (glutamate/Nacetyl-aspartate. Western blot studies were performed to quantify protein nitrosylation (oxidative stress and expression of caspase-3 (apoptosis and TNFα (inflammation.Results: Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on histological damage, was greater than either hypothermia or cannabidiol alone.Conclusion: Cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage.

  11. Gestational Undernourishment Modifies the Composition of Skeletal Muscle Transverse Tubule Membranes and the Mechanical Properties of Muscles in Newborn Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Tonathiu Ramírez-Oseguera

    2013-10-01

    Full Text Available Backgroud/Aims: Skeletal muscle (SM constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4 located in the Transverse tubule membrane system (TT. The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Methods: Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL muscle. Results: We demonstrate that compared to control, GUN in the new-born produces; i decreases body weight; ii diminution in SM mass; iii decreases the formation of TT membranes; iv expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. Conclusion; These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood.

  12. Repetitive exposures to a surrogate nipple providing nutritive and non-nutritive fluids: effects on suckling behavior of the newborn rat.

    Science.gov (United States)

    Petrov, Evgeniy S; Nizhnikov, Michael E; Kozlov, Andrey P; Varlinskaya, Elena I; Kramskaya, Tatiana A; Spear, Norman E

    2004-10-01

    Responsiveness to a surrogate nipple providing water, 0.1% saccharin, 10% sucrose, pedialyte, or milk was tested in naïve-to-suckling newborn rats during six 10-min exposures, one every 1.5 h over a 7.5 h period. Across a succession of exposures, newborn rats repeatedly attached to and ingested milk from a surrogate nipple, yielding significant body weight gain and increased concentration of blood plasma glucose. Initially, pups ingested considerable amounts of saccharin and sucrose, but then dramatically decreased their consumption of these fluids across the experimental sessions. Intake of milk was significantly higher than that of all other substances. Blood glucose concentration in pups treated with water, saccharin, sucrose, and pedialyte did not differ significantly from that of non-treated pups. The present data suggest a potential contribution of a fluid's palatability and nutritive value in the persistence and efficacy of diet intake for neonatal rats in the context of suckling behavior.

  13. Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

    Science.gov (United States)

    Liapi, Charis; Stolakis, Vasileios; Zarros, Apostolos; Zissis, Konstantinos M; Botis, John; Al-Humadi, Hussam; Tsakiris, Stylianos

    2013-11-01

    The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions. These findings could provide the basis for a further evaluation of the herein discussed neurotoxic effects of in utero exposure to Cd, in a brain region-specific manner.

  14. Pharmacotherapeutical reduction of post-hypoxic-ischemic brain injury in the newborn

    NARCIS (Netherlands)

    Peeters, C; van Bel, F

    2001-01-01

    Perinatal hypoxia-ischemia (PHI) is a major cause of morbidity and mortality. A substantial part of PHI-related brain damage occurs upon reperfusion and reoxygenation by the excess production of excitatory amino acids, free (pro)radicals and the release of cytokines, triggering programmed cell death

  15. Automatic MRI-based quantication of brain characteristics in preterm newborns

    NARCIS (Netherlands)

    Moeskops, P.

    2016-01-01

    Even though survival of preterm infants has improved in recent years, preterm birth is still associated with developmental impairments, such as cognitive and behavioural problems. Brain development is particularly vulnerable in this population because an important part of development takes place aft

  16. Newborn jaundice

    Science.gov (United States)

    ... of life for babies sent home from the hospital in 72 hours Alternative Names Jaundice of the newborn; Neonatal hyperbilirubinemia; Bili lights - jaundice; Infant - yellow skin; Newborn - yellow skin Patient Instructions Newborn jaundice - discharge Newborn jaundice - what to ask your doctor Images ...

  17. Neuroglobin expression in rats after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Xin Lin; Min Li; Aijia Shang; Yazhuo Hu; Xiao Yang; Ling Ye; Suyan Bian; Zhongfeng Wang; Dingbiao Zhou

    2012-01-01

    In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex, and peaked at 30 minutes and 48 hours following traumatic brain injury. Immunohistochemical staining demonstrated that neuroglobin expression increased and remained high 2 hours to 5 days following injury. The rate of increase in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury. Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased, while that of the proapoptotic factor decreased, in the cerebral cortex post severe closed traumatic brain injury. It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.

  18. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus Brain

    Directory of Open Access Journals (Sweden)

    Ahmed A. Allam

    2016-01-01

    Full Text Available Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication; Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns.

  19. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain.

    Science.gov (United States)

    Allam, Ahmed A; Maodaa, Salah N; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns.

  20. Distribution of nimodipine in brain following intranasal administration in rats

    Institute of Scientific and Technical Information of China (English)

    Qi-zhi ZHANG; Xin-guo JIANG; Chun-hua WU

    2004-01-01

    AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS:Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively.The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

  1. The effects of sex on brain iron status in rats

    Institute of Scientific and Technical Information of China (English)

    HAO Qian; CHANG Yanzhong

    2015-01-01

    Objective:Iron plays essential roles in the human body. Studies have shown that iron is dis-tributed differently in male and female Rats in liver, spleen, bone marrow, kidney, heart. However, the effects of sex on iron distribution in central nervous system are not well established. Methods:To explore the effects of the above mentioned, in this study, female and male Sprague Dawley rats were used at 4 months of age. The synthesis of ferritin light chain (FTL), transferrin receptor1 (TfR1), ferroportin 1 (FPN1), divalent metal transporter 1 ( DMT1) in the cortex, hippocampus, striatum, cerebellum, and olfactory bulb was determined by Western blot a-nalysis. Results:The results showed that the levels of FTL protein in the cortex, hippocampus, striatum, cerebel-lum, and olfactory bulb were higher in female rats than in male rats, but the levels of TfR1 protein were lower in female rats than in male rats. There was no significant change in FPN1 and DMT1 expression in brain. Conclu-sions:These data suggest that sex have effects on brain iron status. Iron is distributed differently in central nervous system in male and female rats. However, the precise mechanisms need further study.

  2. Spatiotemporal expression patterns of Pax6 in the brain of embryonic, newborn, and adult mice.

    Science.gov (United States)

    Duan, Deyi; Fu, Yuhong; Paxinos, George; Watson, Charles

    2013-03-01

    The transcription factor Pax6 has been reported to specify neural progenitor cell fates during development and maintain neuronal commitments in the adult. The spatiotemporal patterns of Pax6 expression were examined in sagittal and horizontal sections of the embryonic, postnatal, and adult brains using immunohistochemistry and double immunolabeling. The proportion of Pax6-immunopositive cells in various parts of the adult brain was estimated using the isotropic fractionator methodology. It was shown that at embryonic day 11 (E11) Pax6 was robustly expressed in the proliferative neuroepithelia of the ventricular zone in the forebrain and hindbrain, and in the floor and the mesencephalic reticular formation (mRt) in the midbrain. At E12, its expression emerged in the nucleus of the lateral lemniscus in the rhombencephalon and disappeared from the floor of the midbrain. As neurodevelopment proceeds, the expression pattern of Pax6 changes from the mitotic germinal zone in the ventricular zone to become extensively distributed in cell groups in the forebrain and hindbrain, and the expression persisted in the mRt. The majority of Pax6-positive cell groups were maintained until adult life, but the intensity of Pax6 expression became much weaker. Pax6 expression was maintained in the mitotic subventricular zone in the adult brain, but not in the germinal region dentate gyrus in the adult hippocampus. There was no obvious colocalization of Pax6 and NeuN during embryonic development, suggesting Pax6 is found primarily in developing progenitor cells. In the adult brain, however, Pax6 maintains neuronal features of some subtypes of neurons, as indicated by 97.1% of Pax6-positive cells co-expressing NeuN in the cerebellum, 40.7% in the olfactory bulb, 38.3% in the cerebrum, and 73.9% in the remaining brain except the hippocampus. Differentiated tyrosine hydroxylase (TH) neurons were observed in the floor of the E11 midbrain where Pax6 was also expressed, but no obvious

  3. Oxidative damage to rat brain in iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  4. Demonstration of endogenous imipramine like material in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  5. Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.

    Science.gov (United States)

    Ma, W; Cao, Y-Y; Qu, S; Ma, S-S; Wang, J-Z; Deng, L-Q; Yuan, W-J; Meng, J-H

    2016-12-01

    Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test. The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age. Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.

  6. Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

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    Bijaya Upadhyaya

    2017-04-01

    Full Text Available Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0.1. In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1 are associated with the “metabolic process” in general and particularly with “positive regulation of cholesterol biosynthesis” (FDR = 0.03; (2 overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR < 0.1; and (3 are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero.

  7. The effect of chemotherapy on rat brain PET: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)

    2010-10-15

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  8. BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

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    Boris Đinđić

    2003-04-01

    Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

  9. Structural linear measurements in the newborn brain: accuracy of cranial ultrasound compared to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Leijser, Lara M. [Hammersmith Hospital, Imperial College, Department of Paediatrics, London (United Kingdom); Srinivasan, Latha; Cowan, Frances M. [Hammersmith Hospital, Imperial College, Department of Paediatrics, London (United Kingdom); Hammersmith Hospital, Imperial College, Department of Imaging Sciences, London (United Kingdom); Rutherford, Mary A.; Counsell, Serena J.; Allsop, Joanna M. [Hammersmith Hospital, Imperial College, Department of Imaging Sciences, London (United Kingdom)

    2007-07-15

    Structural size in the neonatal brain is of clinical importance. Cranial ultrasonography (cUS) is the primary method used for evaluating the neonatal brain and it is important to know whether linear measurements made using this technique are accurate. To compare linear measurements of different cerebral structures made from neonatal cUS and contemporaneous MRI. Preterm and term infants studies with cUS and MRI on the same day were studied. Linear measurements made using both techniques from many cerebral structures were compared using a paired t-test. A total of 44 sets of scans from 26 preterm and 8 term infants were assessed. Small but significant differences between the cUS and MRI measurements (P<0.05) were found for the ventricular index, the posterior horn depth of the lateral ventricle, the extracerebral space and interhemispheric fissure, and the cortex of the cingulate gyrus. No significant differences were found for any other measurements. Linear measurements from cUS are accurate for most neonatal cerebral structures. Significant differences compared to MRI were found for a few structures, but only for the cortex were the absolute differences marked and possibly of clinical importance. (orig.)

  10. Brain asymmetry modulates perception of biological motion in newborn chicks (Gallus gallus).

    Science.gov (United States)

    Rugani, Rosa; Rosa Salva, Orsola; Regolin, Lucia; Vallortigara, Giorgio

    2015-09-01

    Few light-points on the joints of a moving animal give the impression of biological motion (BM). Day-old chicks prefer BM to non-BM, suggesting a conserved predisposition to attend to moving animals. In humans and other mammals a network of regions, primarily in the right hemisphere, provides the neural substrate for BM perception. However, this has not been investigated in avians. In birds the information from each eye is mainly feeding to the contralateral hemisphere. To study brain asymmetry, we recorded the eye spontaneously used by chicks to inspect a BM stimulus. We also investigated the effect of lateralization following light exposure of the embryos. In Experiment 1, highly lateralized chicks aligned with the apparent direction of motion only when they were exposed to a BM-stimulus moving rightward first, monitoring it with the left-eye-system. In Experiment 2 weakly lateralized chicks did not show any behavioral asymmetry. Moreover, they counter aligned with the apparent direction of motion. Brain lateralization affects chicks behavior while processing and approaching a BM stimulus. Highly lateralized chicks aligned their body with the apparent direction of the BM, a behavior akin to a following response, monitoring the stimulus preferentially with their left eye. This suggests a right hemisphere dominance in BM processing. Weakly lateralized chicks counter-aligned with the apparent direction of the BM, facing it during interaction, and monitored it equally with both eyes. Environmental factors (light stimulation) seem to affect the development of lateralization, and consequently social behavior.

  11. Effects of magnesium sulfate on traumatic brain edema in rats

    Institute of Scientific and Technical Information of China (English)

    冯东福; 朱志安; 卢亦成

    2004-01-01

    Objective: To investigate the effects of magnesium sulfate on traumatic brain edema and explore its possible mechanism.Methods: Forty-eight Sprague-Dawley ( SD ) rats were randomly divided into three groups: Control, Trauma and Treatment groups. In Treatment group, magnesium sulfate was intraperitoneally administered immediately after the induction of brain trauma. At 24 h after trauma, total tissue water content and Na + , K + , Ca2 + , Mg2+ contents were measured. Permeability of blood-brain barrier (BBB)was assessed quantitatively by Evans Blue (EB) dye technique. The pathological changes were also studied.Results: Water, Na + , Ca2 + and EB contents in Treatment group were significantly lower than those in Trauma group ( P < 0. 05 ). Results of light microscopy and electron microscopy confirmed that magnesium sulfate can attenuate traumatic brain injury and relieve BBB injury.Conclusions: Treatment with MgSO4 in the early stage can attenuate traumatic brain edema and prevent BBB injury.

  12. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants,. Inflammatory markers .... were then moved back to their respective dams and immediately ..... various pro-inflammatory cytokines is stimulated.

  13. Arrhenius plots of membrane-bound enzymes of mitochondria and microsomes in the brain cortex of developing and old rats.

    Science.gov (United States)

    Gorgani, M N; Pour-Rahimi, F; Meisami, E

    1986-06-01

    To study changes in lipid-protein-interaction and fluidity in mitochondrial and microsomal membranes of brain during development and aging, the Arrhenius plots of marker enzymes for mitochondrial inner and outer membranes as well as those of microsomal membranes were compared at different ages. The enzymes were, beta-hydroxybutyrate dehydrogenase (BDH) for the inner mitochondrial membrane and rotenone-insensitive-NADH-cytochrome c reductase (Mit-NADH-CytR) for the outer membrane; also antimycin-insensitive-NADH-cytochrome c reductase (Micr-NADH-CytR) and NADPH-cytochrome c reductase for the microsomal membranes. The ages studied were, 1, 5, 30, 60 days postnatal and 2 years. In the microsomes, the plots of NADH-cytochrome c reductase were found to be biphasic at all ages except in the newborn where no break temperature was observed. The activation energy of this enzyme in the physiological range of temperature was found to be high in the newborn, declining with brain maturation. The plot of this enzyme in the old rat showed no difference when compared with the mature. The specific activity of the enzyme, however, was markedly reduced in the old brain microsomal fraction. In contrast, comparison of the plots of microsomal NADPH-cytochrome c reductase at the various ages revealed no break temperature and very similar energies of activation. For the inner mitochondrial membrane beta-hydroxybutyrate dehydrogenase, the Arrhenius plots were generally biphasic at all ages studied with a break temperature of about 20 degrees C. However, the newborn plot was only barely biphasic showing a high energy of activation in the physiological range of temperature. In contrast, for the outer membrane NADH-cytochrome c reductase, the newborn plots were definitely biphasic, exhibiting low activation energy above the breaks. There was also a significant decline in the break temperature with brain development. No significant differences in the plots of this enzyme were found between the

  14. Inducible gene manipulations in brain serotonergic neurons of transgenic rats.

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    Tillmann Weber

    Full Text Available The serotonergic (5-HT system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP, in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system.

  15. Changes in intracellular calcium in brain cells of aged rats

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Yunpeng Cao

    2008-01-01

    BACKGROUND: Studies have shown that voltage-dependent calcium influx, and enhancement of certain calcium-dependent processes in neurons, is related to aging. OBJECTIVE: To observe changes in intracellular calcium ([Ca2+]i) in neurons of aged rats, and to compare with young rats. DESIGN, TIME AND SETTING: A randomized control experiment of neurophysiology was performed at the Central Laboratory of School of Pharmaceutical Science, China Medical University from June to August 2004. MATERIALS: Ten male, healthy, Wistar rats, 19 months old, were selected for the aged group. Ten male, 3-month-old, Wistar rats were selected for the young control group. Fura-2/AM was provided by the Institute of Pharmaceutical Research of Chinese Academy of Medical Sciences, and the F-2000 fluorospectrophotometer was a product of Hitachi, Japan. METHODS: Fluorescence Fura-2 spectrophotometer was used to measure [Ca2+]i in acutely dissociated brain cells of aged and young rats. The concentration of extracellular potassium was controlled by adding different volumes of chloridated potassium solution of high concentration. MAIN OUTCOME MEASURES: [Ca2+]i in neurons of young and aged rats in the presence of 1 mmol/L extracellular calcium concentration and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium. Absolute increase of [Ca2+]i in neurons of young and aged rats when extraceUular potassium was 5,10,20, 40 mmol/L. RESULTS: In the presence of 1 mmol/L extracellular Ca2+ and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium, [Ca2+]i in the neurons of aged rats was significantly less than that in young rats (P 0.05). CONCLUSION: The overload of [Ca2+]i in neurons of aged rats is greater than that of young rats under the same circumstances.

  16. Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe international study.

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    Diego Gazzolo

    Full Text Available Perinatal asphyxia (PA is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury.We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth.S100B salivary levels were significantly (P3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100% and a specificity of 100% (CI5-95%: 98.6%-100% as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0.S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

  17. Cariogenic effect of caffeine intake during lactation on first molars of newborn rats.

    Science.gov (United States)

    Nakamoto, T; Cheuk, S L; Yoshino, S; Falster, A U; Simmons, W B

    1993-10-01

    Lactating dams with eight suckling pups were fed either a 20% protein diet as a control or experimentally a 20% protein diet supplemented with caffeine (2 mg/100g body weight) from the birth of the pups to day 22. At day 22, the pups from both groups were weaned and fed a cariogenic diet until day 50, when they were killed. Dental caries of the molars were scored from randomized mandibles. The enamel of the first molars in the caffeine group showed significantly higher caries scores than that of the controls. This appears to be the first unequivocal evidence that caffeine is a cariogenic agent when newborns are exposed to it during critical periods of tooth development. Therefore, the widespread human consumption of caffeine could be a threat to the healthy development of teeth.

  18. Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

    Directory of Open Access Journals (Sweden)

    G. A. Karkashadze

    2016-01-01

    Full Text Available Hypoxic-ischemic brain lesions in children are the main environmental (non-genetic factor in forming severe neurological pathology with subsequent disability. Scientists see the improvement of therapeutic approaches in acute phase of the disease as a main way to reduce the severity of neurologic complications. Due to the achievements in neuroscience in the field of perinatal hypoxicischemic injury mechanisms, three energy phases of pathologic events deployment were identified: primary (up to 6 hours from the lesion, secondary (6 to 24–48 h after the lesion and distal tertiary (during few weeks, months. At the same time, necrosis, apoptosis, glutamate excitotoxicity, oxidative stress, inflammation, angiogenesis and neurogenesis make up separate links of destruction process. On the basis of new data on the pathogenesis of the disease, scientists from different countries have already offered modern treatment methods for perinatal hypoxic-ischemic injury with erythropoietin, allopurinol, melatonin, N-acetylcysteine, magnesium sulphate, albumin, -interferon, as well as with the help of controlled hypothermia, xenon, the use of stem cells, etc. This article presents a review of new data on pathogenesis and promising treatment methods for perinatal hypoxic-ischemic injuries.

  19. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  20. Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

    Science.gov (United States)

    Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Expression of neuropeptide Y in rat brain ischemia

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    Babović Siniša S.

    2013-01-01

    Full Text Available Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum - especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack.

  2. Nerve growth factor receptor molecules in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Taniuchi, M.; Schweitzer, J.B.; Johnson, E.M. Jr.

    1986-03-01

    The authors have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking /sup 125/I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. They applied the /sup 125/I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of rat brain: NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. They also observed retrograde transport of /sup 125/I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

  3. Preserved modular network organization in the sedated rat brain.

    Directory of Open Access Journals (Sweden)

    Dany V D'Souza

    Full Text Available Translation of resting-state functional connectivity (FC magnetic resonance imaging (rs-fMRI applications from human to rodents has experienced growing interest, and bears a great potential in pre-clinical imaging as it enables assessing non-invasively the topological organization of complex FC networks (FCNs in rodent models under normal and various pathophysiological conditions. However, to date, little is known about the organizational architecture of FCNs in rodents in a mentally healthy state, although an understanding of the same is of paramount importance before investigating networks under compromised states. In this study, we characterized the properties of resting-state FCN in an extensive number of Sprague-Dawley rats (n = 40 under medetomidine sedation by evaluating its modular organization and centrality of brain regions and tested for reproducibility. Fully-connected large-scale complex networks of positively and negatively weighted connections were constructed based on Pearson partial correlation analysis between the time courses of 36 brain regions encompassing almost the entire brain. Applying recently proposed complex network analysis measures, we show that the rat FCN exhibits a modular architecture, comprising six modules with a high between subject reproducibility. In addition, we identified network hubs with strong connections to diverse brain regions. Overall our results obtained under a straight medetomidine protocol show for the first time that the community structure of the rat brain is preserved under pharmacologically induced sedation with a network modularity contrasting from the one reported for deep anesthesia but closely resembles the organization described for the rat in conscious state.

  4. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    Science.gov (United States)

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  5. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  6. Noninvasive method to assess the electrical brain activity from rats

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    Rosana Ferrari

    2013-10-01

    Full Text Available This research presents a noninvasive method for the acquisition of brain electrical signal in rat. Was used an electroencephalography (EEG system developed for bovine and adapted to rats. The bipolar electrode system (needle electrodes was glued on the surface of the head of the animal without surgical procedures and the other electrode was glued to the tail, as ground. The EEG activity was sampled at 120Hz for an hour. The accuracy and precision of the EEG measurement was performed using Fourier analysis and signal energy. For this, the digital signal was divided into sections successive of 3 seconds and was decomposed into four frequency bands: delta (0.3 to 4Hz, theta (4-8Hz, alpha (8-12Hz and beta (12-30Hz and energy (µV² of the series of time filtered were calculated. The method allowed the acquisition of non-invasive electrical brain signals in conscious rats and their frequency patterns were in agreement with previous studies that used surgical procedures to acquire EEG in rats. This system showed accuracy and precision and will allow further studies on behavior and to investigate the action of drugs on the central nervous system in rats without surgical procedures.

  7. Determination of sevoflurane minimum alveolar concentration in newborn and adult rats%新生及成年大鼠七氟醚 MAC 值的测定

    Institute of Scientific and Technical Information of China (English)

    黄艳; 杨小霖; 黄三

    2016-01-01

    Objective To measure and compare sevoflurane minimum alveolar concentration (MAC)in newborn and adult rats.Methods The rats were divided into newborn rat (6-8 days) group (25 cases)and adult rat (8-10 weeks)group (25 cases).All rats were settled in the self-made device for anesthesia with inhaled sevoflurane,and the tails of rats were exposed out of the device. Sevoflurane was given via an anesthesia machine.Up-and-down method and clamping tail stimulus were applied to measure the MAC values of sevoflurane in the two groups.1.5% of sevoflurane was set as the initial concentration,and± 0.2% as adjustable gradient.A positive or negative response was judged by clamping tail stimulus in a 20 minutes interval.The mean MAC value of all rats in each group was defined as the MAC value.Results The MAC value of newborn rats was (2.58 ± 0.1 1)%,and the MAC value of adult rats was (2.32 ±0.13)%.A significant difference was found between the two groups (P <0.01).Conclusion The MAC value of newborn rats was much higher than that of adult rats.Newborn rats need a higher concentration of sevoflurane at the same depth of anesthesia when compared with adult rats.%目的:测定并比较新生及成年大鼠七氟醚的最低肺泡有效浓度(MAC)。方法选择健康新生及成年 SD 大鼠各25只。两组大鼠分别放入自制大鼠麻醉装置,露出其尾部。七氟醚气体经麻醉机挥发罐输入麻醉装置。采用序贯法及夹尾刺激测定七氟醚 MAC。七氟醚初始测定浓度为1.5%,调节梯度为±0.2%。每间隔20 min 重复夹尾试验判断麻醉效果并抽取气体样本3~5 ml 测定七氟醚浓度。如此反复,使每只大鼠均获得一个阳性与阴性反应的交叉点。组内每只大鼠 MAC值的均值即为该组大鼠的 MAC 值。结果新生大鼠 MAC 值为(2.58±0.11)%,明显高于成年大鼠的 MAC 值(2.32±0.13)%(P <0.01)。结论新生大鼠的七氟醚 MAC 值明显高于成年大鼠,达到同一麻醉深度时

  8. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

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    Strazielle Nathalie

    2008-03-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  9. Differential Expression of Sirtuins in the Ageing Rat Brain

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    Gilles J. Guillemin

    2015-05-01

    Full Text Available Although there are seven mammalian sirtuins (SIRT1-7, little is known about their expression in the ageing brain. To characterise the change(s in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of ‘physiologically’ aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy ageing.

  10. Molecular cloning of partial cDNAs for rat DNA topoisomerase II isoforms and their differential expression in brain development.

    Science.gov (United States)

    Tsutsui, K; Tsutsui, K; Okada, S; Watanabe, M; Shohmori, T; Seki, S; Inoue, Y

    1993-09-05

    cDNA segments for DNA topoisomerase II were amplified from rat brain RNA after reverse transcription by the polymerase chain reaction, using degenerate oligonucleotide primers deduced from the conserved regions of topoisomerase II of higher eukaryotes. The cDNA product from a successful amplification was homogeneous in length but heterogeneous in sequence. Restriction mapping of the cloned cDNA fragments revealed that they consisted of two distinct sequence groups. DNA sequencing of representative clones from each group, designated A and B, showed that they are highly homologous to cDNAs of human topoisomerase II isoforms, alpha and beta, respectively. Northern blot analysis indicated that the transcript level for rat topoisomerase II alpha was high in embryonic brain and in the cerebellum of 2-day newborns, followed by rapid decrease to a undetectable level at 4 weeks after birth. In contrast, rat topoisomerase II beta transcript was present throughout the embryonic and postnatal stages. In the developing cerebellum, cells expressing topoisomerase II alpha were confirmed exclusively to the outer mitotic zone of the external granular layer, whereas the transcript of topoisomerase II beta was detected over the entire cortical region. These results clearly indicate that the isoform alpha is expressed only in proliferating cells. The differential expression of topoisomerase II isozymes was also observed among developed tissues. Therefore, the isozymes are most likely to be involved in the following different physiological processes: topoisomerase II alpha in cell proliferation, and topoisomerase II beta in some processes unrelated to cell proliferation.

  11. Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid.

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    Gioia Altobelli

    Full Text Available A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%. The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.

  12. Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains

    Institute of Scientific and Technical Information of China (English)

    唐涛; 黎杏群; 武衡; 罗杰坤; 张花先; 罗团连

    2004-01-01

    Background Many researchers suggest that adult mammalian central nervous system (CNS) is incapable of completing self-repair or regeneration. And there are accumulating lines of evidence which suggest that endogenous neural stem cells (NSCs) are activated in many pathological conditions, including stroke in the past decades, which might partly account for rehabilitation afterwards. In this study, we investigated whether there was endogenous neural stem cell activation in intracerebral hemorrhagic (ICH) rat brains.Methods After ICH induction by stereotactical injection of collagenase type Ⅶ into globus pallidus, 5-Bromo-2 Deoxyuridine (BrdU) was administered intraperitoneally to label newborn cells. Immunohistochemical method was used to detect Nestin, a marker for neural stem cells, and BrdU.Results Nestin-positive or BrdU-Labeled cells were predominantly located at 2 sites: basal ganglion around hemotoma, ependyma and nearby subventricular zone (SVZ). No positive cells for the 2 markers were found in the 2 sites of normal control group and sham group, as well as in non-leisoned parenchyma, both hippocampi and olfactory bulbs in the 4 groups. Nestin+ cells presented 4 types of morphology, and BrdU+ nucleus were polymorphologic. Postive cell counting around hemotoma showed that at day 2, Nestin+ cells were seen around hemotoma in model group , the number of which increased at day 4, day 7(P<0.01), peaked at day 14(P<0.05), and reduced significantly by day 28(P<0.01).Conclusion Endogenous neural stem cells were activated in experimental intracerebral hemorrhagic rat brains.

  13. Direct in vivo cell lineage analysis in the retrorsine and 2AAF models of liver injury after genetic labeling in adult and newborn rats.

    Directory of Open Access Journals (Sweden)

    Virginie Pichard

    Full Text Available BACKGROUNDS AND AIMS: When hepatocyte proliferation is impaired, liver regeneration proceeds from the division of non parenchymal hepatocyte progenitors. Oval cells and Small Hepatocyte-like Progenitor Cells (SHPCs represent the two most studied examples of such epithelial cells with putative stem cell capacity. In the present study we wished to compare the origin of SHPCs proliferating after retrorsine administration to the one of oval cells observed after 2-Acetyl-Amino fluorene (2-AAF treatment. METHODOLOGY/PRINCIPAL FINDINGS: We used retroviral-mediated nlslacZ genetic labeling of dividing cells to study the fate of cells in the liver. Labeling was performed either in adult rats before treatment or in newborn animals. Labeled cells were identified and characterised by immunohistochemistry. In adult-labeled animals, labeling was restricted to mature hepatocytes. Retrorsine treatment did not modify the overall number of labeled cells in the liver whereas after 2-AAF administration unlabeled oval cells were recorded and the total number of labeled cells decreased significantly. When labeling was performed in newborn rats, results after retrorsine administration were identical to those obtained in adult-labeled rats. In contrast, in the 2-AAF regimen numerous labeled oval cells were present and were able to generate new labeled hepatocytes. Furthermore, we also observed labeled biliary tracts in 2-AAF treated rats. CONCLUSIONS: Our results strongly suggest that SHPCs are derived from hepatocytes and we confirm that SHPCs and oval cells do not share the same origin. We also show that hepatic progenitors are labeled in newborn rats suggesting future directions for in vivo lineage studies.

  14. Orexin-A expression in dissociated neuronal cultures of the newborn rat cortex

    NARCIS (Netherlands)

    Stoyanova, I.; Feber, le J.; Wiertz, R.W.F.; Rutten, W.L.C.

    2009-01-01

    Orexin A is a neuropeptide isolated from a small group of neurons in the hypothalamus, which orchestrates many different brain functions. Despite the extensive information about orexin A expression and function in the nervous system of adults, data about the formation and maturation of the orexin sy

  15. Postnatal development of aminopeptidase (arylamidase) activity in rat brain.

    Science.gov (United States)

    de Gandarias, J M; Ramírez, M; Zulaica, J; Iribar, C; Casis, L

    1989-01-01

    Changes in the activities of Leu- and Arg-arylamidase in rat frontal and parietal cortices and the subcortical area (including thalamus, hypothalamus, and striatum) were examined in the 2nd, 4th, 8th, 12th, and 24th weeks of life. Average levels found in the subcortical region were greater than those in the cortical areas. The most marked changes in enzymatic activity in the course of brain development were found in the subcortical structure. Leu-arylamidase activity increased from the 2nd week up to the 8th week, returning to the 2nd week level at the 12th and 24th weeks. The maximum levels of Arg-arylamidase activity were found at the 4th and 8th weeks. These data suggest that proteolytic activity is involved in the postnatal development of rat brain.

  16. Nerve protective effect of rhTPO and G-CSF on hypoxic ischemic brain damage in rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Zhou; Chun-Lai Zhang; Yue-Hong Li; Yu-Xin Zhang; Zi-Feng Wei; Xi Wang Meng Ling-Li

    2014-01-01

    Objective:To observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage(HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible.Methods:A total of120 newbornSD rats aging7 d were randomly divided into control group, model group,TPO group andG-CSF group, using the method of blockingleft carotid artery to establishHIBD model.The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment andG-CSF treatment were adopted in the model group,TPO group andG-CSF group respectively.Then10 rats of4 groups were executed atDay3,7,14 after modeling, brain tissue was extracted to observe the brain damage;Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein(nestin) expression.Results:Injured brain mass of model group,TPO group andG-CSF group were significantly higher than that of control group at corresponding time point(P<0.05).Injured brain mass ofTPO group andG-CSF group were significantly lower than that of model group(P<0.05), and with the increase of age, more significant increasing trend.AtDay3 after modeling, the expression of nestin positive cells in cerebral cortex of model group,TPO group andG-CSF group increased significantly than that of control group(P<0.05); nestin positive cells ofG-CSF group outnumberedTPO group significantly (P<0.05).Conclusions:The earlyTPO,G-CSF treatment ofHIBD rats can improve brain function after hypoxia ischemia by neural protection.G-CSF can promote the differentiation of neural cells proliferation, and reduce degeneration and necrosis of nerve cells.

  17. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

    Institute of Scientific and Technical Information of China (English)

    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

  18. Altered vestibular function in fetal and newborn rats gestated in space

    Science.gov (United States)

    Ronca, A. E.; Alberts, J. R.

    1997-01-01

    Researchers evaluated vestibular development and function in rat pups flown during gestation on the NASA-NIH R1 and R2 missions. Fetal and postnatal vestibular function were examined. Altered vestibular-mediated responses in the experimental fetal pups are attributed to either direct effect of gravity on the vestibular system or indirect effects of microgravity transduced through the mother. The postnatal tests confirmed the hypothesis that the vestibular system continually adapts and responds to tonic stimulation.

  19. Effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    许民辉; 代文光; 邓洵鼎

    2002-01-01

    Objective: To study the effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury and the possible mechanism.Methods: The middle degree brain injury in rats was made by BIM-III multi-function impacting machine. The brain mitochondrial respiratory function was measured with oxygen electrode and the ultra-structural changes were observed with transmission electron microscope (TEM).Results: 1. The brain mitochondrial respiratory stage III and respiration control rate reduced significantly in the untreated groups within 24 and 72 hours. But treated Group A showed certain degree of recovery of respiratory function; treated Group B showed further improvement. 2. Untreated Group, treated Groups A and B had different degrees of mitochondrial ultra-structural damage respectively, which could be attenuated after the treatment with magnesium sulfate.Conclusions: The mitochondrial respiratory function decreases significantly after traumatic brain injury. But it can be apparently improved after magnesium sulfate management along with the attenuated damage of mitochondria discovered by TEM. The longer course of treatment can obtain a better improvement of mitochondrial respiratory function.

  20. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  1. Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation.

    Science.gov (United States)

    García-Calatayud, Salvador; Redondo, Carlos; Martín, Eva; Ruiz, José Ignacio; García-Fuentes, Miguel; Sanjurjo, Pablo

    2005-05-01

    N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

  2. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  3. Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹

    2004-01-01

    @@ Marrow stromal cells(MSCs) have been reported to transplant into injured brain via intravenous or intraarterial or direct intracerebral administration.1-3 In the present study, we observed that MSCs migrated into the brain, survived and diffeneriated into neural cells after they were injected into the cisterna magna of rats, and that the behavior of the rats after traumatic brain injury (TBI) was improved.

  4. Brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Chroni, Elisabeth; Patsoukis, Nikolaos; Karageorgos, Nikolaos; Konstantinou, Dimitris; Georgiou, Christos

    2006-02-01

    The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

  5. Gelation and fodrin purification from rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Péron-Renner, M; Coffe, G; Pudles, J

    1986-06-03

    Extracts from rat brain tissue have been shown to give rise to a gel which exhibits the following features. It is mainly enriched in actin and in a high-molecular-weight protein with polypeptide chains of 235 and 240 kDa, which we identified as fodrin. Tubulin is also a major component of the gel but it appears to be trapped non-specifically during the gelation process. Gelation is pH-, ionic strength- and Ca2+-concentration-dependent, and is optimal under the conditions which promote the interaction between polymerized actin and fodrin. In a similar way to that described for the purification of rat brain actin (Levilliers, N., Péron-Renner, M., Coffe, G. and Pudles, J. (1984) Biochimie 66, 531-537), we used the gelation system as a selective means of recovering fodrin from the mixture of a low-ionic-strength extract from whole rat brain and a high-ionic-strength extract of the particulate fraction. From this gel, fodrin was purified with a good yield by a simple procedure involving gel dissociation in 0.5 M KCl and depolymerization in 0.7 M KI, Bio-Gel A-15m chromatography, followed by ammonium sulfate precipitation.

  6. Carbofuran Modulating Functions of Acetylcholinesterase from Rat Brain In Vitro

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Gupta

    2016-01-01

    Full Text Available Carbofuran, a potential environmental xenobiotic, has the ability to cross blood brain barrier and to adversely influence brain functions. In the present study, the impact of carbofuran on the biophysical and biochemical properties of rat brain AChE has been evaluated in vitro. This enzyme was membrane-bound which could be solubilised using Triton-X100 (0.2%, v/v, a nonionic detergent, in the extraction buffer (50 mM phosphate, pH 7.4. The enzyme was highly stable up to one month when stored at -20°C and exhibited optimum activity at pH 7.4 and 37°C. AChE displayed a direct relationship between activity and varying substrate concentrations (acetylthiocholine iodide (ATI by following Michaelis-Menten curve. The Km and Vmax values as computed from the Lineweaver-Burk double reciprocal plot of the data were found to be 0.07 mM and 0.066 µmole/mL/min, respectively. The enzyme exhibited IC50 value for carbofuran equal to 6.0 nM. The steady-state kinetic studies to determine mode of action of carbofuran on rat brain AChE displayed it to be noncompetitive in nature with Ki value equal to 5 nm. These experiments suggested that rat brain AChE was very sensitive to carbofuran and this enzyme might serve as a significant biomarker of carbofuran induced neurotoxicity.

  7. Oxymatrine reduces neuroinflammation in rat brain A signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Jiahui Mao; Yae Hu; Ailing Zhou; Bing Zheng; Yi Liu; Yueming Du; Jia Li; Jinyang Lu; Pengcheng Zhou

    2012-01-01

    Cerebral neuroinflammation models were established by injecting 10 μg lipopolysaccharide into the hippocampus of male Sprague-Dawley rats.The rats were treated with an intraperitoneal injection of 120,90,or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection.Twenty-four hours after model induction,the hippocampus was analyzed by real-time quantitative PCR,and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay.The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine.Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine.Additionally,120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-kB p65 in the nucleus and of phosphorylated IkBα in the cytoplasm of brain cells,as detected by western blot assay.Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-kB signaling pathway.

  8. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    Science.gov (United States)

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.

  9. Hypothermia and room air resuscitation in NT2-N neurons, immature rats and newborn pigs

    OpenAIRE

    2011-01-01

    Perinatal asphyxia remains one of the major causes of perinatal mortality and morbidity worldwide. Mild therapeutic hypothermia reduces brain injury after perinatal asphyxia. There is an ongoing search for strategies to further improve outcome, including best practice resuscitation and interventions that can be used in combination with hypothermia. The use of supplemental oxygen during resuscitation causes a number of harmful effects including increased cerebral injury. It is not known whethe...

  10. Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

    Science.gov (United States)

    Quiróz, Ubaldo; Morales-Ledesma, Leticia; Morán, Carolina; Trujillo, Angélica; Domínguez, Roberto

    2014-06-01

    There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH.

  11. Effects of protein malnutrition on oxidative status in rat brain.

    Science.gov (United States)

    Feoli, Ana M; Siqueira, Ionara R; Almeida, Lúcia; Tramontina, Ana C; Vanzella, Cláudia; Sbaraini, Sabrina; Schweigert, Ingrid D; Netto, Carlos A; Perry, Marcos L S; Gonçalves, Carlos A

    2006-02-01

    This study evaluated the effects of protein malnutrition on oxidative status in rat brain areas. We investigated various parameters of oxidative status, free radical content (dichlorofluorescein formation), indexes of damage to lipid (thiobarbituric acid-reactive substances assay), and protein damage (tryptophan and tyrosine content) in addition to total antioxidant reactivity levels and antioxidant enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase in different cerebral regions (cortex, hippocampus, and cerebellum) from rats subjected to prenatal and postnatal protein malnutrition (control 25% casein and protein malnutrition 7% casein). Protein malnutrition altered various parameters of oxidative stress, especially damage to macromolecules. Free radical content was unchanged by protein malnutrition. There was an increase in levels of thiobarbituric acid-reactive substances, the index of lipid peroxidation, in the cerebellum and cerebral cortex (P brain structures (P malnutrition increased oxidative damage to lipids and proteins from the studied brain areas. These results may be an indication of an important mechanism for changes in brain development that are caused by protein malnutrition.

  12. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    Science.gov (United States)

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  13. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    Science.gov (United States)

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

  14. Distinct transcriptional changes in donor kidneys upon brain death induction in rats : Insights in the processes of brain death

    NARCIS (Netherlands)

    Schuurs, TA; Gerbens, F; van der Hoeven, JAB; Ottens, PJ; Kooi, KA; Leuvenink, HGD; Hofstra, RMW; Ploeg, RJ

    2004-01-01

    Brain death affects hormone regulation, inflammatory reactivity and hemodynamic stability. In transplant models, donor organs retrieved from brain dead (BD) rats suffer from increased rates of primary nonfunction and lower graft survival. To unravel the mechanisms behind brain death we have performe

  15. Influence of histidine on zinc transport into rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto [Shizuoka Univ. (Japan). School of Pharmaceutical Sciences

    2000-06-01

    The brain of rats injected intravenously with {sup 65}Zn-His or {sup 65}ZnCl{sub 2} was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from {sup 65}Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from {sup 65}Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of {sup 65}Zn-His in the brain was similar to that of {sup 65}ZnCl{sub 2} group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the {sup 65}Zn-His group from the blood was higher than that of the {sup 65}ZnCl{sub 2} group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  16. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  17. Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat.

    Directory of Open Access Journals (Sweden)

    Myriam Antri

    Full Text Available Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca(2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat.

  18. Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury.

    Science.gov (United States)

    Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Post, Jeremy; Baldwin, Katherine; Hoffer, Barry; Balaban, Carey D; Barbacci, Damon; Schultz, J Albert; Gouty, Shawn; Cox, Brian M; Woods, Amina S

    2016-10-15

    Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50μm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments. Copyright © 2016. Published by Elsevier B.V.

  19. Primary culture and identification of sinoatrial node cells from newborn rat

    Institute of Scientific and Technical Information of China (English)

    宋治远; 钟理; 仝识非; 何国祥

    2003-01-01

    Objective To establish a reliable approach to primary culture and identification of sinoatrial node (SAN) cells. Methods The SAN cells were cultured from SAN tissue removed from neonatal Wistar rats and purified with differential attachment and 5'-bromodeoxyuridine (BrdU) treatment. The obtained cells were morphologically observed with inverted microscopy and transmission electron microscopy. Its action potential was recorded using electrophysiological methods.Results Three distinctly different cells were observed in the cultured SAN cells: spindle, triangle and irregular. Of these, the spindle cells comprised the greatest proportion, with their shape, structure and electrophysiological characteristics consistent with those of the pacemaker cells of SAN. The triangle cells were similar in features to the similarly shaped myocytes located in the atrial myocardium. Conclusions The culture method of differential attachment combined with BrdU treatment is a reliable approach to growing SAN cells. Of the cells cultured from SAN, the spindle cells appear to function as pacemaker cells.

  20. Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass.

    Science.gov (United States)

    Xu, Tao; Li, Wenjie; Liang, Yiqun; Yang, Zhonghua; Liu, Jingdong; Wang, Yejun; Su, Nailun

    2014-11-01

    Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.

  1. Contribution of Ca2+-dependent conductances to membrane potential fluctuations of medullary respiratory neurons of newborn rats in vitro.

    Science.gov (United States)

    Onimaru, Hiroshi; Ballanyi, Klaus; Homma, Ikuo

    2003-11-01

    Ca2+-dependent conductances were studied in respiratory interneurons in the brainstem-spinal cord preparation of newborn rats. omega-Conotoxin-GVIA attenuated evoked postsynaptic potentials, spontaneous or evoked inspiratory spinal nerve activity and blocked spike afterhyperpolarization. Furthermore, omega-conotoxin-GVIA augmented rhythmic drive potentials of pre-inspiratory and inspiratory neurons and increased respiratory-related spike frequency of pre-inspiratory cells with no effect on inspiratory hyperpolarization. In contrast, omega-agatoxin-IVA depressed drive potentials of pre-inspiratory and inspiratory neurons and attenuated inspiratory hyperpolarization and spike frequency of pre-inspiratory cells. It did not affect spike shape and exerted only minor, non-significant, attenuating effects on spontaneous or evoked nerve bursts or evoked postsynaptic potentials. Nifedipine diminished drive potentials and spike frequency of pre-inspiratory neurons and shortened drive potentials in some cells. omega-Conotoxin-MVIIC attenuated drive potentials and intraburst firing rate of pre-inspiratory neurons and decreased substantially respiratory frequency. Respiratory rhythm disappeared following combined application of omega-conotoxin-GVIA, omega-conotoxin-MVIIC, omega-agatoxin-IVA and nifedipine. Apamin potentiated drive potentials and abolished spike afterhyperpolarization, whereas charybdotoxin and tetraethylammonium prolonged spike duration without effect on shape of drive potentials. The results show that specific sets of voltage-activated L-, N- and P/Q-type Ca2+ channels determine the activity of particular subclasses of neonatal respiratory neurons, whereas SK- and BK-type K+ channels attenuate drive potentials and shorten spikes, respectively, independent of cell type. We hypothesize that modulation of spontaneous activity of pre-inspiratory neurons via N-, L- and P/Q-type Ca2+ channels is important for respiratory rhythm or pattern generation.

  2. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    Science.gov (United States)

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions.

  3. In utero exposure to microwave radiation and rat brain development.

    Science.gov (United States)

    Merritt, J H; Hardy, K A; Chamness, A F

    1984-01-01

    Timed-pregnancy rats were exposed in a circular waveguide system starting on day 2 of gestation. The system operated at 2,450 MHz (pulsed waves; 8 microseconds PW; 830 pps). Specific absorption rate (SAR) was maintained at 0.4 W/kg by increasing the input power as the animals grew in size. On day 18 of gestation the dams were removed from the waveguide cages and euthanized; the fetuses were removed and weighed. Fetal brains were excised and weighed, and brain RNA, DNA and protein were determined. Values for measured parameters of the radiated fetuses did not differ significantly from those of sham-exposed fetuses. A regression of brain weight on body weight showed no micrencephalous fetuses in the radiation group when using as a criterion a regression line based on two standard errors of the estimate of the sham-exposed group. In addition, metrics derived from brain DNA (ie, cell number and cell size) showed no significant differences when radiation was compared to sham exposure. We conclude that 2,450-MHz microwave radiation, at an SAR of 0.4 W/kg, did not produce significant alterations in brain organogenesis.

  4. Gene Expression Profiling during Pregnancy in Rat Brain Tissue.

    Science.gov (United States)

    Mann, Phyllis E

    2014-03-04

    The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases "expectant brain" and "maternal brain". Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  5. Characteristics of muscarinic acetylcholine receptors in rat brain.

    Directory of Open Access Journals (Sweden)

    Nukina,Itaru

    1983-06-01

    Full Text Available Characteristics of muscarinic acetylcholine (ACh receptors were studied in the rat central nervous system (CNS using 3H-quinuclidinyl benzilate (QNB, an antagonist of muscarinic ACh receptors. Scatchard analysis indicated that the rat CNS had a single 3H-QNB binding site with an apparent dissociation constant (Kd of 5.0 X 10(-10 M. Li+, Zn++ and Cu++ had strong effects on 3H-QNB binding which indicates that these metal ions might play important roles at muscarinic ACh receptor sites in the brain. Since antidepressants and antischizophrenic drugs displaced the binding of 3H-QNB, the anticholinergic effects of these drugs need to be taken into account when they are applied clinically. The muscarinic ACh receptor was successfully solubilized with lysophosphatidylcholine. By gel chromatography, with a Sepharose 6B column, the solubilized muscarinic ACh receptor molecule eluted at the fraction corresponding to a Stokes' radius of 6.1 nm. With the use of sucrose-density-gradient centrifugation, the molecular weight of the solubilized muscarinic ACh receptor was determined to be about 90,000 daltons. The regional distribution of 3H-QNB binding in rat brain was examined, and the highest level of 3H-QNB binding was found to be in the striatum followed by cerebral cortex and hippocampus, indicating that muscarinic ACh mechanisms affect CNS function mainly through these areas.

  6. Measurement of tritiated norepinephrine metabolism in intact rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Levitt, M.; Kowalik, S.; Barkai, A.I. (New York State Psychiatric Inst., New York (USA))

    1983-06-01

    A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing (/sup 3/H)NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in the rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism.

  7. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    Science.gov (United States)

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  8. eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Xing Hua Tang

    Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

  9. Unilateral whisker trimming in newborn rats alters neuronal coincident discharge among mature barrel cortex neurons.

    Science.gov (United States)

    Ghoshal, Ayan; Lustig, Brian; Popescu, Maria; Ebner, Ford; Pouget, Pierre

    2014-10-15

    It is known that sensory deprivation, including postnatal whisker trimming, can lead to severe deficits in the firing rate properties of cortical neurons. Recent results indicate that development of synchronous discharge among cortical neurons is also activity influenced, and that correlated discharge is significantly impaired following loss of bilateral sensory input in rats. Here we investigate whether unilateral whisker trimming (unilateral deprivation or UD) after birth interferes in the same way with the development of synchronous discharge in cortex. We measured the coincidence of spikes among pairs of neurons recorded under urethane anesthesia in one whisker barrel field deprived by trimming all contralateral whiskers for 60 days after birth (UD), and in untrimmed controls (CON). In the septal columns around barrels, UD significantly increased the coincident discharge among cortical neurons compared with CON, most notably in layers II/III. In contrast, synchronous discharge was normal between layer IV UD barrel neurons: i.e., not different from CON. Thus, while bilateral whisker deprivation (BD) produced a global deficit in the development of synchrony in layer IV, UD did not block the development of synchrony between neurons in layer IV barrels and increased synchrony within septal circuits. We conclude that changes in synchronous discharge after UD are unexpectedly different from those recorded after BD, and we speculate that this effect may be due to the driven activity from active commissural inputs arising from the contralateral hemisphere that received normal activity levels during postnatal development. Copyright © 2014 the American Physiological Society.

  10. Cerebrolysin attenuates blood-brain barrier and brain pathology following whole body hyperthermia in the rat.

    Science.gov (United States)

    Sharma, Hari Shanker; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Johanson, Conrad E

    2010-01-01

    The possibility that Cerebrolysin, a mixture of several neurotrophic factors, has some neuroprotective effects on whole body hyperthermia (WBH) induced breakdown of the blood-brain barrier (BBB), blood-CSF barrier (BCSFB), brain edema formation and neuropathology were examined in a rat model. Rats subjected to a 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited profound increases in BBB and BCSFB permeability to Evans blue and radioiodine tracers compared to controls. Hippocampus, caudate nucleus, thalamus and hypothalamus exhibited pronounced increase in water content and brain pathology following 4 h heat stress. Pretreatment with Cerebrolysin (1, 2 or 5 mL/kg i.v.) 24 h before WBH significantly attenuated breakdown of the BBB or BCSFB and brain edema formation. This effect was dose dependent. Interestingly, the cell and tissue injury following WBH in cerebrolysin-treated groups were also considerably reduced. These novel observations suggest that cerebrolysin can attenuate WBH induced BBB and BCSFB damage resulting in neuroprotection.

  11. Parvalbumin immunoreactivity is enhanced by brain-derived neurotrophic factor in organotypic cultures of rat retina.

    Science.gov (United States)

    Rickman, D W

    1999-11-15

    The rodent retina undergoes considerable postnatal neurogenesis and phenotypic differentiation, and it is likely that diffusible neurotrophic factors contribute to this development and to the subsequent formation of functional retinal circuitry. Accordingly, perturbation of specific neurotrophin ligand-receptor interactions has provided valuable information as to the fundamental processes underlying this development. In the present studies we have built upon our previous observation that suppression of expression of trk(B), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), in the postnatal rat retina results in the alteration of a specific interneuron in the rod pathway-the parvalbumin (PV)-immunoreactive AII amacrine cell. Here, we isolated retinas from newborn rats and maintained them in organotypic culture for up to 14 days (approximating the time of eye opening, in vivo) in the presence of individual neurotrophins [BDNF or nerve growth factor (NGF)]. We then examined histological sections of cultures for PV immunoreactivity. In control cultures, only sparse PV-immunostained cells were observed. In cultures supplemented with NGF, numerous lightly immunostained somata were present in the inner nuclear layer (INL) at the border of the inner plexiform layer (IPL). Many of these cells had rudimentary dendritic arborizations in the IPL. Cultures supplemented with BDNF displayed numerous well-immunostained somata at the INL/IPL border that gave rise to elaborate dendritic arborizations that approximated the morphology of mature AII amacrine cells in vivo. These observations indicate that neurotrophins have specific effects upon the neurochemical and, perhaps, morphological differentiation of an important interneuron in a specific functional retinal circuit.

  12. The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

    Directory of Open Access Journals (Sweden)

    S. Pejic

    2003-05-01

    Full Text Available The sensitivity of copper,zinc (CuZn- and manganese (Mn-superoxide dismutase (SOD to exogenous estradiol benzoate (EB was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 µg EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%, 8 (72.7% and 15 (81.7%. In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6% disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively. EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8% changed to an inhibitory effect on day 8 (38.4% and disappeared by day 45 when inhibition was detected again (48.7%. In males, the inhibitory effect on this enzyme was observed on days 0 (45.0% and 15 (28.9%, and then disappeared until day 60 when a stimulatory effect was observed (38.4%. EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process.

  13. Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.

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    Céline Méhats

    Full Text Available BACKGROUND: Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. METHODOLOGY/FINDINGS: Rat pups were placed under hyperoxia (FiO2>95% or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. CONCLUSIONS: Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization.

  14. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  15. Properties of Opiate-Receptor Binding in Rat Brain

    Science.gov (United States)

    Pert, Candace B.; Snyder, Solomon H.

    1973-01-01

    [3H]Naloxone, a potent opiate antagonist, binds stereospecifically to opiate-receptor sites in rat-brain tissue. The binding is time, temperature, and pH dependent and saturable with respect to [3H]naloxone and tissue concentration. The [3H]naloxone-receptor complex formation is bimolecular with a dissociation constant of 20 nM. 15 Opiate agonists and antagonists compete for the same receptors, whose density is 30 pmol/g. Potencies of opiates and their antagonists in displacing [3H]naloxone binding parallel their pharmacological potencies. PMID:4525427

  16. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte

    2010-01-01

    BACKGROUND/AIMS: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB(1)), the serotonin receptor 2C...... positively correlated with visceral fat mass. Risperidone treatment increased CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA. CONCLUSION: The present study...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  17. Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

    1998-03-01

    Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

  18. 胎儿炎症反应与早产儿脑损伤%Fetal inflammatory response and brain injury in preterm newborns

    Institute of Scientific and Technical Information of China (English)

    马江林

    2014-01-01

    宫内感染后胎儿炎症反应在早产及早产儿脑损伤中发挥重要作用.胎儿炎症反应表现为胎儿循环中前炎症细胞因子增加.炎症信号可通过血脑屏障启动胎儿神经炎症反应,导致发育中大脑损伤.全面理解胎儿炎症反应有助于提出干预措施并改善早产儿神经发育结局.该文就胎儿炎症反应与早产儿脑损伤相关问题作一综述.%The fetal inflammatory response to intrauterine infection plays a crucial role in the pathogenesis of preterm birth and preterm brain injury.The fetal inflammatory response is characterized by elevated levels of proinflammatory cytokines in the fetal circulation.The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response and triggers damage in the developing brain.A better understanding of the fetal inflammatory response will help design interventions to improve neurodevelopmental outcomes after preterm birth.This review summarizes researches of fetal inflammatory response and brain injury in the preterm newborn.

  19. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

    Energy Technology Data Exchange (ETDEWEB)

    Doormaal, Pieter Jan van [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands); Meander Medical Center Amersfoort, Department of Radiology, PO Box 1502, Amersfoort (Netherlands); Meiners, Linda C.; Sijens, Paul E. [University Medical Center Groningen and University of Groningen, Department of Radiology, Groningen (Netherlands); Horst, Hendrik J. ter; Veere, Christa N. van der [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands)

    2012-04-15

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. (orig.)

  20. Plasminogen activator inhibitor-1 mitigates brain injury in a rat model of infection-sensitized neonatal hypoxia-ischemia.

    Science.gov (United States)

    Yang, Dianer; Sun, Yu-Yo; Nemkul, Niza; Baumann, Jessica M; Shereen, Ahmed; Dunn, R Scott; Wills-Karp, Marsha; Lawrence, Daniel A; Lindquist, Diana M; Kuan, Chia-Yi

    2013-05-01

    Intrauterine infection exacerbates neonatal hypoxic-ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inflammatory cytokines in newborn brains. Remarkably, these pathogenic responses were all blocked by intracerebroventricular injection of a stable-mutant form of plasminogen activator protein-1 called CPAI. Similarly, LPS pre-exposure amplified, while CPAI therapy mitigated HI-induced blood-brain-barrier damage and the brain tissue loss with a therapeutic window at 4 h after the LPS/HI insult. The CPAI also blocks microglia activation following a brain injection of LPS, which requires the contribution by tPA, but not the urinary-type plasminogen activator (uPA), as shown by experiments in tPA-null and uPA-null mice. These results implicate the nonproteolytic tPA activity in LPS/HI-induced brain damage and microglia activation. Finally, the CPAI treatment protects near-normal motor and white matter development despite neonatal LPS/HI insult. Together, because CPAI blocks both proteolytic and nonproteolytic tPA neurotoxicity, it is a promising therapeutics of neonatal HI injury either with or without infection.

  1. Is beat induction innate or learned? Probing emergent meter perception in adults and newborns using event-related brain potentials.

    Science.gov (United States)

    Honing, Henkjan; Ladinig, Olivia; Háden, Gábor P; Winkler, István

    2009-07-01

    Meter is considered an important structuring mechanism in the perception and experience of rhythm in music. Combining behavioral and electrophysiological measures, in the present study we investigate whether meter is more likely a learned phenomenon, possibly a result of musical expertise, or whether sensitivity to meter is also active in adult nonmusicians and newborn infants. The results provide evidence that meter induction is active in adult nonmusicians and that beat induction is already functional right after birth.

  2. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  3. Distribution of the mRNA for protein phosphatase T in rat brain

    NARCIS (Netherlands)

    Becker, W; Buttini, M; Limonta, S; Boddeke, H; Joost, HG

    1996-01-01

    We have recently cloned a novel protein serine/threonine phosphatase (PPT) from rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol. Chem., 269 (1994) 22586-22592). In the present study, the regional distribution of PPT mRNA in the brain of adult rats was characterized by

  4. Distribution of the mRNA for protein phosphatase T in rat brain

    NARCIS (Netherlands)

    Becker, W; Buttini, M; Limonta, S; Boddeke, H; Joost, HG

    1996-01-01

    We have recently cloned a novel protein serine/threonine phosphatase (PPT) from rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol. Chem., 269 (1994) 22586-22592). In the present study, the regional distribution of PPT mRNA in the brain of adult rats was characterized by

  5. Role of stanniocalcin1 in brain injury of coal-burning-borne fluorosis rats

    Institute of Scientific and Technical Information of China (English)

    陈旭义

    2013-01-01

    Objective To observe the change of stanniocalcin 1(STC1) and calcium content in brain of coal-burning-borne fluorosis rats,and to explore the role of STC1 in brain injury of coal-burning-borne fluorosis.Methods Twenty four male SD rats were randomly divided into control,low,medium,

  6. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  7. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

    Directory of Open Access Journals (Sweden)

    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  8. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    Directory of Open Access Journals (Sweden)

    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  9. DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

    Institute of Scientific and Technical Information of China (English)

    YING XIAO; LING WANG; RUO-JUN XU; ZHEN-YU CHEN

    2006-01-01

    Objective To examine the effect of docosahexaenoic acid (DHA) deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain. DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze (MWM) was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain. The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Conclusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

  10. Whole-body new-born and young rats' exposure assessment in a reverberating chamber operating at 2.4 GHz

    Science.gov (United States)

    Wu, Tongning; Hadjem, Abdelhamid; Wong, Man-Fai; Gati, Azzedine; Picon, Odile; Wiart, Joe

    2010-03-01

    This paper presents the whole-body specific absorption rate (WBSAR) assessment of embryos and new-born rats' exposure in a reverberating chamber (RC) operating at 2.4 GHz (WiFi). The finite difference in time domain (FDTD) method often used in bio-electromagnetism is facing very slow convergence. A new simulation-measurement hybrid approach has been proposed to characterize the incident power related to the RC and the WBSAR in rats, which are linked by the mean squared electric field strength in the working volume. Peak localized SAR in the rat under exposure is not included in the content of the study. Detailed parameters of this approach are determined by simulations. Evolutions for the physical and physiological parameters of the small rats at different ages are discussed. Simulations have been made to analyse all the variability factors contributing to the global results. WBSAR information and the variability for rats at different ages are also discussed in the paper.

  11. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    Science.gov (United States)

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  12. NO-tryptophan: a new small molecule located in the rat brain

    Directory of Open Access Journals (Sweden)

    A. Mangas

    2016-09-01

    Full Text Available A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W with good affinity (10-9 M and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. 

  13. NO-tryptophan: a new small molecule located in the rat brain.

    Science.gov (United States)

    Mangas, A; Yajeya, J; González, N; Duleu, S; Geffard, M; Coveñas, R

    2016-09-22

    A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms.

  14. Pain indicators in newborns

    Directory of Open Access Journals (Sweden)

    Spasojević Slobodan

    2008-01-01

    Full Text Available Definition of pain. The International Association for the Study of Pain has defined pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage." The interpretation of pain is subjective. Each person forms an internal construct of pain through encountered injury. Pain and newborn. The issue of pain perception in newborns, its management and prevention has been neglected for decades. The inability of "self-report" of painful experience has contributed significantly to misunderstanding of the importance of this problem and in­adequate treatment. The main characteristic of this 'critical window of brain development' period is rapid enlargement of brain volume and its great plasticity. Harmful short-term and long-term consequences can arise as a consequence of disturbance of the sophisticated balance between newborn and its surrounding. Neonatal pain indicators. As a response to a present painful stimulus, the newborn adapts to this acute stress with changes in endocrine, vegetative, immune and behavioral area. An ideal pain indicator in neonatal period does not exist. There are several different groups o them, namely contextual and developmental indicators (gestational age, contributed illness, medication, for example, physiological (heart rate, vagal tone, breathing rate, blood pressure, oxygen saturation, transcutaneous partial pressures of oxygen and carbon-dioxide, intracranial pressure, palm sweating and behavioral ones (face expression, movements of limbs, cry, several neonatal pain scales were constructed on the basis of these indicators. .

  15. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...

  16. Anticancer and antioxidant properties of terpinolene in rat brain cells.

    Science.gov (United States)

    Aydin, Elanur; Türkez, Hasan; Taşdemir, Sener

    2013-09-01

    Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

  17. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  18. Inhibition of lipid peroxidation in rat brain by nifedipine and clorazepate after electrically induced seizures.

    Science.gov (United States)

    Kułak, W; Sobaniec, W; Sobaniec-Lotowska, M

    1993-01-01

    The effect of nifedipine and clorazepate on the concentration of lipid peroxides (LP) in rat brain, and the characteristics of electrically induced seizures were assessed. A significant increase in the concentration of brain LP after electroshock was found. Both nifedipine (1.00 mg/kg per os) and clorazepate (20 mg/kg intraperitoneally) decreased the levels of LP in the rat brain after electroshock. Nifedipine combined with clorazepate brought an inhibition of LP formation and an additive anticonvulsant activity.

  19. Selective glial vulnerability following transient global ischemia in rat brain.

    Science.gov (United States)

    Petito, C K; Olarte, J P; Roberts, B; Nowak, T S; Pulsinelli, W A

    1998-03-01

    Global cerebral ischemia selectively damages neurons, but its contribution to glial cell death is uncertain. Accordingly, adult male rats were sacrificed by perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic (PI) day 3, but minor or no damage to neurons in other regions. In situ end labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia, astrocytes, and microglia were present in control brain. Apoptotic bodies and ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p < 0.05), but were similar to controls in other regions and at other PI intervals. Most were oligodendroglia, although ISEL-positive microglia and astrocytes were also observed. These results show that oligodendroglia die rapidly after brief global ischemia and are more sensitive than neurons in certain brain regions. Their selective vulnerability to ischemia may be responsible for the delayed white matter damage following anoxia or CO poisoning or that associated with white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders of apoptotic oligonucleosomes that have been found in post-ischemic brain.

  20. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  1. Quinolinic acid induces oxidative stress in rat brain synaptosomes.

    Science.gov (United States)

    Santamaría, A; Galván-Arzate, S; Lisý, V; Ali, S F; Duhart, H M; Osorio-Rico, L; Ríos, C; St'astný, F

    2001-03-26

    The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

  2. Newborn brain event-related potentials revealing atypical processing of sound frequency and the subsequent association with later literacy skills in children with familial dyslexia.

    Science.gov (United States)

    Leppänen, Paavo H T; Hämäläinen, Jarmo A; Salminen, Hanne K; Eklund, Kenneth M; Guttorm, Tomi K; Lohvansuu, Kaisa; Puolakanaho, Anne; Lyytinen, Heikki

    2010-01-01

    The role played by an auditory-processing deficit in dyslexia has been debated for several decades. In a longitudinal study using brain event-related potentials (ERPs) we investigated 1) whether dyslexic children with familial risk background would show atypical pitch processing from birth and 2) how these newborn ERPs later relate to these same children's pre-reading cognitive skills and literacy outcomes. Auditory ERPs were measured at birth for tones varying in pitch and presented in an oddball paradigm (1100 Hz, 12%, and 1000 Hz, 88%). The brain responses of the typically reading control group children (TRC group, N=25) showed clear differentiation between the frequencies, while those of the group of reading disability with familial risk (RDFR, 8 children) and the group of typical readers with familial risk (TRFR, 14 children) did not differentiate between the tones. The ERPs of the latter two groups differed from those of the TRC group. However, the two risk groups also showed a differential hemispheric ERP pattern. Furthermore, newborn ERPs reflecting passive change detection were associated with phonological skills and letter knowledge prior to school age and with phoneme duration perception, reading speed (RS) and spelling accuracy in the 2nd grade of school. The early obligatory response was associated with more general pre-school language skills, as well as with RS and reading accuracy (RA). Results suggest that a proportion of dyslexic readers with familial risk background are affected by atypical auditory processing. This is already present at birth and also relates to pre-reading phonological processing and speech perception. These early differences in auditory processing could later affect phonological representations and reading development. However, atypical auditory processing is unlikely to suffice as a sole explanation for dyslexia but rather as one risk factor, dependent on the genetic profile of the child. Copyright © 2010 Elsevier Srl. All

  3. Thyrotropin-releasing hormone (TRH) depolarizes a subset of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    was accompanied by an increase in spontaneous excitatory synaptic activity that disappeared late during the TRH application. The duration of the inspiratory potentials was increased, indicating that the hypoglossal motoneurons received a longer duration synaptic input from the respiratory rhythm generator. 4...... markedly during TRH. Four cells showed a transient depolarization with an increase in input resistance during TRH with TTX present in the superfusing solution. Thus type-3 neurons are depolarized postsynaptically by TRH. 7. We conclude that TRH increases the frequency of the respiratory rhythm in newborn...

  4. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    Science.gov (United States)

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  5. Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype.

    Science.gov (United States)

    Pacelli, Consiglia; Coluccia, Addolorata; Grattagliano, Ignazio; Cocco, Tiziana; Petrosillo, Giuseppe; Paradies, Giuseppe; De Nitto, Emanuele; Massaro, Antonio; Persichella, Michele; Borracci, Pietro; Portincasa, Piero; Carratù, Maria Rosaria

    2010-06-01

    Dietary choline deprivation (CD) is associated with behavioral changes, but mechanisms underlying these detrimental effects are not well characterized. For instance, no literature data are available concerning the CD effects on brain mitochondrial function related to impairment in cognition. Therefore, we investigated brain mitochondrial function and redox status in male Wistar rats fed a CD diet for 28 d. Moreover, the CD behavioral phenotype was characterized. Compared with rats fed a control diet (CTRL), CD rats showed lower NAD-dependent mitochondrial state III and state IV respiration, 40% lower complex I activity, and significantly higher reactive oxygen species production. Total glutathione was oxidatively consumed more in CD than in CTRL rats and the rate of protein oxidation was 40% higher in CD than in CTRL rats, reflecting an oxidative stress condition. The mitochondrial concentrations of cardiolipin, a phospholipid required for optimal activity of complex I, was 20% lower in CD rats than in CTRL rats. Compared with CTRL rats, the behavioral phenotype of CD rats was characterized by impairment in motor coordination and motor learning assessed with the rotarod/accelerod test. Furthermore, compared with CTRL rats, CD rats were less capable of learning the active avoidance task and the number of attempts they made to avoid foot shock was fewer. The results suggest that CD-induced dysfunction in brain mitochondria may be responsible for impairment in cognition and underline that, similar to the liver, the brain also needs an adequate choline supply for its normal functioning.

  6. Lipopolysaccharide-induced expression of IP-10 mRNA in rat brain and in cultured rat astrocytes and microglia

    NARCIS (Netherlands)

    Ren, LQ; Gourmala, N; Boddeke, HWGM; Gebicke-Haerter, PJ

    1998-01-01

    Using mRNA differential display technique, we have found a differentially expressed band in rat brain, designated HAP(2)G1, which was the strongest one induced in response to peripheral administration of lipopolysaccharide (LPS). Sequence analysis showed that HAP(2)G1 cDNA is the rat homologue of th

  7. Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus

    OpenAIRE

    2012-01-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns. GMH causes neurological sequelae such as cerebral palsy, post-hemorrhagic hydrocephalus, and mental retardation. Despite this, there is no standardized animal model of spontaneous GMH using newborn rats to depict the condition. We asked whether stereotactic injection of collagenase type VII (0.3 U) into the ganglionic eminence of neonatal rats would reproduce the acute brain injury, gliosis, hydroc...

  8. Angiotensin II type 2 receptor ligand PD123319 attenuates hyperoxia-induced lung and heart injury at a low dose in newborn rats.

    Science.gov (United States)

    Wagenaar, Gerry T M; Sengers, Rozemarijn M A; Laghmani, El Houari; Chen, Xueyu; Lindeboom, Melissa P H A; Roks, Anton J M; Folkerts, Gert; Walther, Frans J

    2014-08-01

    Intervening in angiotensin (Ang)-II type 2 receptor (AT2) signaling may have therapeutic potential for bronchopulmonary dysplasia (BPD) by attenuating lung inflammation and preventing arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We first investigated the role of AT2 inhibition with PD123319 (0.5 and 2 mg·kg(-1)·day(-1)) on the beneficial effect of AT2 agonist LP2-3 (5 μg/kg twice a day) on RVH in newborn rats with hyperoxia-induced BPD. Next we determined the cardiopulmonary effects of PD123319 (0.1 mg·kg(-1)·day(-1)) in two 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 lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression. Ten days of coadministration of LP2-3 and PD123319 abolished the beneficial effects of LP2-3 on RVH in experimental BPD. In the early treatment model PD123319 attenuated cardiopulmonary injury by reducing alveolar septal thickness, pulmonary influx of inflammatory cells, including macrophages and neutrophils, medial wall thickness of small arterioles, and extravascular collagen III deposition, and by preventing RVH. In the late treatment model PD123319 diminished PAH and RVH, demonstrating that PAH is reversible in the neonatal period. At high concentrations PD123319 blocks the beneficial effects of the AT2-agonist LP2-3 on RVH. At low concentrations PD123319 attenuates cardiopulmonary injury by reducing pulmonary inflammation and fibrosis and preventing PAH-induced RVH but does not affect alveolar and vascular development in newborn rats with experimental BPD.

  9. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio [Niigata Univ. (Japan). Brain Research Inst.

    2001-12-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  10. Label-free dopamine imaging in live rat brain slices.

    Science.gov (United States)

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  11. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  12. Antioxidant effects of calcium antagonists in rat brain homogenates.

    Science.gov (United States)

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T

    2000-06-01

    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  13. Localization and labeling of rat brain in MR image based on Paxinos-Watson atlas

    Science.gov (United States)

    Cao, Jie; Cai, Chao; Ding, Mingyue; Zhou, Chengping

    2006-03-01

    Localization and labeling of function regions in brain is an important topic in experimental brain sciences because the huge amount of data collected by neuroscientists will become meaningless if we cannot give them a precise description of their locations. In this paper, we proposed a localization and labelling method of 3D MR image of rat brain based on Paxinos-Watson atlas. Our objective is to use the specific atlas to accomplish localization and labeling of specified tissue of interest (TOI) to mimic a veteran expert such that invisible or unclear anatomic function regions in the MR images of rat brain can be automatically identified and marked. We proposed a multi-step method to locate and label the TOIs from the MR image of rat brain. Firstly, pre-processing. It aims at the digitization and 3D reconstruction of the atlas and MRI of rat brain. Secondly, two-step registration. The global registration is to eliminate the big misalign and section angle offset as well as the scale between the MRI and atlas. We can choose some unambiguous and characteristic points manually, and based on these correspondences a coarse registration is obtained using affine model. The local registration is to address individual variability of rat brain that can be performed by using Snake model. Thirdly, post-processing. The goal is to locate and label the TOIs in the selected MR image of rat brain slice guided by well-registered atlas. The experiments demonstrated the feasibility of our method.

  14. Regional protein synthesis in rat brain following acute hemispheric ischemia.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  15. The quantitative analysis of S100 in the brain tissue and serum following diffuse brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Wang Qi; Huang Ping; Xing Bo; Tuo Ya; Zhang Yongpan; Tian Weiping; Wang Zhenyuan

    2007-01-01

    Objective To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0.5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.

  16. Adenovirally Delivered Brain-derived Neurotrophic Factor to Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Xu Hou; Dan Hu; Yannian Hui

    2004-01-01

    Purpose: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus.Methods: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining, and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA).Results: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point(P < 0.01 ), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01 ).Conclusion: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

  17. Anemia in the Newborn

    Science.gov (United States)

    ... Doctor About Emotional Struggles Additional Content Medical News Anemia in the Newborn By Arthur E. Kopelman, MD, ... of Prematurity Necrotizing Enterocolitis (NEC) Jaundice in Newborns Anemia in the Newborn Polycythemia in the Newborn Thyroid ...

  18. The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

    Science.gov (United States)

    Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

    2014-09-12

    Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

  19. Protocatechuic acid protects brain mitochondrial function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Semaming, Yoswaris; Sripetchwandee, Jirapas; Sa-Nguanmoo, Piangkwan; Pintana, Hiranya; Pannangpetch, Patchareewan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-10-01

    Brain mitochondrial dysfunction has been demonstrated in diabetic animals with neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin, has been shown to exert glycemic control and oxidative stress reduction in the heart. However, its effects on oxidative stress and mitochondrial function in the brain under diabetic condition have never been investigated. We found that PCA exerted glycemic control, attenuates brain mitochondrial dysfunction, and contributes to the prevention of brain oxidative stress in diabetic rats.

  20. Regional energy balance in rat brain after transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1983-05-01

    Phosphocreatine, ATP, and glucose were severely depleted, and the lactate levels were increased in the paramedian neocortex, dorsal-lateral striatum, and CA1 zone of hippocampus of rats exposed to 30 min of forebrain ischemia. Upon recirculation of the brain, phosphocreatine, ATP, and lactate concentrations recovered to control values in the paramedian neocortex and CA1 zone of hippocampus and to near-control values in the striatum. The phosphocreatine and ATP concentrations then fell and the lactate levels rose in the striatum after 6-24 h, and in the CA1 zone of hippocampus after 24-72 h. The initial recovery and subsequent delayed changes in the phosphocreatine, ATP, and lactate concentrations in the striatum and hippocampus coincided with the onset and progression of morphological injury in these brain regions. The results suggest that cells in these regions regain normal or near-normal mitochondrial function and are viable, in terms of energy production, for many hours before unknown mechanisms cause irreversible neuronal before unknown mechanisms cause irreversible neuronal injury.

  1. Rat brain aryl acylamidase: further characterization of multiple forms.

    Science.gov (United States)

    Hsu, L L; Halaris, A E; Freedman, D X

    1982-01-01

    1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

  2. Effect of ethanol on enkephalinergic opioid system of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Belyayev, N.A.; Balakireva, N.N.; Brusov, O.S.; Panchenko, L.F.

    1983-10-13

    Specific binding of /sup 3/H-morphine and /sup 3/H-(D-Ala/sup 2/, D-Leu/sup 5/)-enkephalin (H-EN) with opiatic receptors was studied on white rats along with the content of Met- and Leu-enkephalin and the activity of enkephalinase in various brain segments after single dose (20% solution in 0.9% NaCl, IP; 1.5-4.5 g/kg body weight) and chronic injection (20% EtOH substituted for drinking water) of ethanol. The single injection of EtOH (1.5-4.5 g/kg) resulted in a depression of the specific binding of H-EN with opiate receptors. Doses of 1.5 and 2.5 g/kg led to a lower content of Leu-enkephalin in mid-brain but to an increase of Met-enkephalin; the 4.5 g/kg dose had no effect on the striatum. With chronic administration of EtOH, most of the values obtained on the experimental animals were similar to the control data. 23 references.

  3. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  4. Are soluble and membrane-bound rat brain acetylcholinesterase different

    Energy Technology Data Exchange (ETDEWEB)

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. (Centre de Neurochimie du C.N.R.S., Strasbourg, (France))

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  5. Brain Metabolic Changes in Rats following Acoustic Trauma

    Science.gov (United States)

    He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

    2017-01-01

    Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine

  6. Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.

    Science.gov (United States)

    Yuan, Jing; Wang, Aihua; He, Yan; Si, Zhihua; Xu, Shan; Zhang, Shanchao; Wang, Kun; Wang, Dawei; Liu, Yiming

    2016-10-01

    Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  8. Brain lipids in rats fed a diet supplemented with hen eggs of modified lipid content

    Directory of Open Access Journals (Sweden)

    Hodžić Aida

    2012-01-01

    Full Text Available The aim of this study was to research the impact of a diet supplemented with egg yolks of modified content, having in mind the type of fat added to the laying hens diet, on the brain lipids and their fatty acid composition in rats. During four weeks of the experiment, 64 Wistar rats, divided into four groups of 16 animals each (eight animals of both sexes, were fed the commercial rat feed (group C, or the feed that contained 70% of the commercial rat feed and 30% of freshly boiled yolks from the eggs originating from laying hens fed with 3% fish oil (group F, 3% palm olein (group P or 3% lard (group L. Concentration and content of total lipids and total cholesterol, as well as the fatty-acid composition of the total brain lipids were determined in the lipid extracts of the rats brains. Under unfavourable conditions, which in our case could be high dietary intake of the total fat due to egg yolk addition, the amount of total fat in the brain tissue or the mass of the organ itself can be changed. Applied dietary treatments could also influence the level of de novo synthesis of total cholesterol in the rat brain. High dietary fat intake, as well as the fat quality regarding its fatty acid composition, appear to be able to significantly influence the fatty acid profile of the total brain lipids in adult rats, whereas the level and quality of the changes also depend on sex.

  9. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    Science.gov (United States)

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  10. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    Science.gov (United States)

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

  11. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  12. Irradiation of rat brain reduces P-glycoprotein expression and function

    OpenAIRE

    Bart, J.; Nagengast, W B; Coppes, R P; Wegman, T D; van der Graaf, W T A; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N.H.

    2007-01-01

    The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats wer...

  13. Yawning and stretching predict brain temperature changes in rats:Support for the thermoregulatory hypothesis

    Directory of Open Access Journals (Sweden)

    Melanie L Shoup-Knox

    2010-09-01

    Full Text Available Recent research suggests that yawning is an adaptive behavior that functions to promote brain thermoregulation among homeotherms. To explore the relationship between brain temperature and yawning we implanted thermocoupled probes in the frontal cortex of rats to measure brain temperature before, during and after yawning. Temperature recordings indicate that yawns and stretches occurred during increases in brain temperature, with brain temperatures being restored to baseline following the execution of each of these behaviors. The circulatory changes that accompany yawning and stretching may explain some of the thermal similarities surrounding these events. These results suggest that yawning and stretching may serve to maintain brain thermal homeostasis.

  14. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    In vitro models of the blood-brain barrier are useful tools to study blood-brain barrier function as well as drug permeation from the systemic circulation to the brain parenchyma. However, a large number of the available in vitro models fail to reflect the tightness of the in vivo blood-brain...... barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  15. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats.

    Science.gov (United States)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  16. Localization profile of Cathepsin L in the brain of African giant rat ...

    African Journals Online (AJOL)

    Localization profile of Cathepsin L in the brain of African giant rat ( Cricestomys gambianus ) ... Log in or Register to get access to full text downloads. ... Within the diencephalon high density of positive signals was observed in mediodorsal and ...

  17. Catechins decrease neurological severity score through apoptosis and neurotropic factor pathway in rat traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Retty Ratnawati

    2017-08-01

    Administration of catechins decreased NSS through inhibiting inflammation and apoptosis, as well as induced the neurotrophic factors in rat brain injury. Catechins may serve as a potential intervention for TBI.

  18. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  19. Protective effects of melatonin on the ionizing radiation induced DNA damage in the rat brain.

    Science.gov (United States)

    Undeger, Ulko; Giray, Belma; Zorlu, A Faruk; Oge, Kamil; Baçaran, Nurçen

    2004-03-01

    Melatonin is an endogenously produced antioxidant with radioprotective actions while ionizing radiation is a well-known cytotoxic and mutagenic agent of which the biological results are attributable to its free radical producing effects. The effect of melatonin on the DNA strand breakage and lipid peroxidation induced by ionizing radiation in the rat brain were investigated in order to clarify its radioprotective ability. The DNA strand breakage in rat brain exposed to 1000 cGy ionizing radiation was assessed by alkaline single cell gel electrophoresis and the lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) concentrations. A significant increase in DNA damage (p radiation treated rat brain. Pre-treatment of rats with intraperitoneal doses of 100 mg/kg melatonin provided a significant decrease in the DNA strand breakage and lipid peroxidation. Our results indicate that melatonin can protect brain cells from oxidative damage induced by ionizing radiation.

  20. Changing Numbers of Neuronal and Non-Neuronal Cells Underlie Postnatal Brain Growth in the Rat

    National Research Council Canada - National Science Library

    Fabiana Bandeira; Roberto Lent; Suzana Herculano-Houzel; Jon H. Kaas

    2009-01-01

    .... To test this hypothesis, here we investigate quantitatively the postnatal changes in the total number of neuronal and non-neuronal cells in the developing rat brain, and examine how these changes...

  1. The expression of TRPA1 mRNA in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Peng Du; Shua Li; Jinyu Zheng; Zhi-yuan Yu; Minjie Xie; Wei Wang

    2006-01-01

    Objective: To investigate the distribution of TRPA1 (one kind of the TRP-like ion channel family) channel in the hippocampus and cerebral cortex of rat. Methods: RT-PCR was used to amplify the fragment of TRPA1 in the DRG (dorsal root ganglion), hippocampus and cerebral cortex of adult SD rat. In situ hybridization staining was used to show the distribution of TRPA1 mRNA in the hippocampus and cerebral cortex of adult rat brain. Results: Both RT-PCR and in situ hybridization staining showed that TRPA1 mRNA was expressed in hippocampus and cerebral cortex of the adult rat brain. Conclusion: Ourresults suggest that there is expression of TRPA1 mRNA both in the hippocampus and cerebral cortex of the adult rat brain.

  2. BRAIN VOLUMES OF THE LAMB, RAT AND BIRD DO NOT SHOW HEMISPHERIC ASYMMETRY: A STEREOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    Bünyamin Sahin

    2011-05-01

    Full Text Available It is well known that there are functional differences between right and left brain hemispheres. However, it is not clear whether these functional differences are reflected in morphometric differences. This study was carried out to investigate the right-left asymmetry, and sex and species differences of the brains using the Cavalieri principle for volume estimation. Seventeen lambs, 10 rats and 12 avian brains were used to estimate brain volumes. A transparent point grid was superimposed on the slices of lamb brains directly and the slices of the rat and avian brains were projected onto a screen at 10x magnification. Surface areas of the cut slice faces were estimated by simply counting the points that hit the slices. Mean brain volumes were 37.74 cm3, 598.95 mm3 and 730.38 mm3 and the coefficients of variations were 0.08, 0.05 and 0.05 for lamb, rat and avian brains respectively. The differences between left and right hemispheres did not show statistical significance (P > 0.05. However, the male brain volumes were larger than the females for the lamb and bird (P < 0.05. In light of such findings, it will be necessary to evaluate neuron number of the brain hemispheres to provide more useful data regarding inter-hemispheric brain asymmetry.

  3. Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

    DEFF Research Database (Denmark)

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... the five NCAM mRNAs in rat brain....

  4. Increased expression of aquaporin-4 in brain tissue of amygdala-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Yinghui Chen; Yongbo Zhao

    2011-01-01

    Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures.We hypothesized that the expression of the brain water channel aquaporin-4 (AQP-4) may be upregulated in the epileptic brain.In the present study, we established the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats.We found that AQP-4 was overexpressed in the cerebral cortex of rats with epilepsy compared with controls.These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.

  5. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

    Institute of Scientific and Technical Information of China (English)

    Cai-zhen YAN; Yan-ning HOU

    2004-01-01

    AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain,which suggests that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.

  6. Large litters rearing changes brain expression of GLUT3 and acetylcholinesterase activity in adult rats.

    Science.gov (United States)

    de Vasconcelos, Vivian Sarmento; Machado, Sonia Salgueiro; Guedes, Rubem Carlos Araújo; Bandeira, Bruno Carneiro; Ximenes-da-Silva, Adriana

    2012-09-06

    Effects of malnutrition in the brain are more pronounced during the period of growth spurt, corresponding to the suckling in rodents. Neuronal glucose transporter GLUT3 expression and acetylcholinesterase activity were studied in the brain of adult young rats (84 days old) suckled in litters formed by 6 (control group) or 12 pups (malnourished group). In the adult rats, brain weight, blood glucose levels and GLUT3 expression were decreased in malnourished group (5%, 18%, 58%, respectively, Pmalnutrition during suckling period decreased GLUT3 expression and increased acetylcholinesterase activity in the rat brain that could contribute to possible cognitive deficits and changes of brain metabolic activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    Science.gov (United States)

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  8. Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paravrtamol intoxication

    Institute of Scientific and Technical Information of China (English)

    Camila Scorticati; Juan P. Prestifilippo; Francisco X. Eizayaga; José L. Castro; Salvador Romay; Maria A. Fernández; Abraham Lemberg; Juan C. Perazzo

    2004-01-01

    AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats were divided into four groups. Group Ⅰ: sham operation; Ⅱ: Prehepatic portal hypertension, produced by partial portal vein ligation; Ⅲ:Acetaminophen intoxication and Ⅳ: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.RESULTS: Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ. Liver enzymes and ammonia plasma levels were increased in groups Ⅱ, Ⅳ and Ⅳ. Prehepatic portal hypertension (group Ⅱ), acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ. Behavioral test (rota rod) was altered in group Ⅳ.CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group Ⅳ, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.

  9. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  10. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  11. Cerebrovascular disease in newborn infants: report of three cases with clinical follow-up and brain SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moura-Ribeiro, Maria Valeriana L. de; Ciasca, Sylvia Maria; Vale-Cavalcanti, Mariza; Etchebehere, Elba C.S.C.; Camargo, Edwaldo E. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas

    1999-07-01

    The clinical and neurological findings of three neonates with the diagnosis of cerebrovascular disease are reported. The neuropsychological evaluation disclosed impairment of fine motor function, coordination, language, perception and behavioral disturbances. Brain SPECT imaging revealed perfusional deficits in the three cases. (author)

  12. Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

    Science.gov (United States)

    Veraart, Jelle; Leergaard, Trygve B; Antonsen, Bjørnar T; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G Allan; Verhoye, Marleen; Sijbers, Jan

    2011-10-15

    Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

  13. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non

  14. Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain

    NARCIS (Netherlands)

    Eekelen, J.A.M. van; Kiss, J.Z.; Westphal, H.M.; Kloet, E.R. de

    1987-01-01

    The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stre

  15. Expression of annexin and Annexin-mRNA in rat brain under influence of steroid drugs

    NARCIS (Netherlands)

    Voermans, PH; Go, KG; ter Horst, GJ; Ruiters, MHJ; Solito, E; Parente, L; James, HE; Marshall, LF; Reulen, HJ; Baethmann, A; Marmarou, A; Ito, U; Hoff, JT; Kuroiwa, T; Czernicki, Z

    1997-01-01

    Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of Annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase pr

  16. Comparative proteomics of rat brain in the BCNU-induced model of cortical dysplasia

    Institute of Scientific and Technical Information of China (English)

    郭谊

    2014-01-01

    Objective To screen the differential proteins in the brain(neocortex and hippocampus)between the rats with cortical dysplasia(CD)and control ones,and investigate the role of their alteration in the development of epilepsy in CD.Methods Cortical dysplasia was induced in rat pups via in utero delivery of BCNU.A two-dimensional electrophoresis

  17. The effects of trypsin on rat brain astrocyte activation.

    Directory of Open Access Journals (Sweden)

    Masoud Fereidoni

    2013-12-01

    Full Text Available Astrocytes are cells within the central nervous system which are activated in a wide spectrum of infections, and autoimmune and neurodegenerative diseases. In pathologic states, they produce inflammatory cytokines, chemokines, and nitric oxide (NO, and sometimes they induce apoptosis. Their protease-activated receptors (PARs can be activated by proteases, e.g. thrombin and trypsin, which are important in brain inflammation. The current study aimed to investigate the effects of different concentrations of trypsin (1 to 100U/ml on cultured astrocytes.In the present study, two-day rat infants' brains were isolated and homogenized after meninges removal, then cultivated in DMEM + 10% FBS medium. 10 days later, astrocytes were harvested and recultivated for more purification (up to 95%, using Immunocytochemistry method, in order to be employed for tests. They were affected by different concentrations of trypsin (1, 5, 10, 15, 20, 40, 60, 80, and 100 U/ml. To reveal the inflammation progress, NO concentrations (the Griess test were assessed after 24 and 48 hours.The results showed that trypsin concentration up to 20 U/ml caused a significant increase in NO, in a dose-dependent manner, on cultured astrocytes (P < 0.001. Trypsin 20 U/ml increased NO production fivefold the control group (P < 0.001. At higher concentrations than 20 U/ml, NO production diminished (P < 0.001. At 100 U/ml, NO production was less than the control group (P < 0.001.Inflammatory effects of trypsin 5-20 U/ml are probably due to the stimulation of astrocytes' PAR-2 receptors and the increasing of the activation of NF-κB, PKC, MAPKs. Stimulation of astrocytes' PAR-2 receptors causes an increase in iNOS activation which in turn leads to NO production. However, higher trypsin concentration possibly made astrocyte apoptosis; therefore, NO production diminished. These assumptions need to be further investigated.

  18. The metabolism of malate by cultured rat brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. (Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA))

    1990-12-01

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  19. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

    Science.gov (United States)

    Servatius, Richard J; Marx, Christine E; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D; Naylor, Jennifer C; Pang, Kevin C H

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  20. Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Richard J Servatius

    2016-08-01

    Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  1. Serial Post-mortem Relaxometry in the Normal Rat Brain and Following Stroke

    OpenAIRE

    Fagan, Andrew J.; Mullin, JM; Gallagher, L; Hadley, DM; Macrae, IM; Condon, B

    2008-01-01

    PUBLISHED Purpose: Investigation of MRI for non-invasive autopsy via measurements of serial changes in relaxation parameters of the rat brain during the post-mortem interval. Materials and Methods: Post-mortem relaxometry measurements were performed before and hourly after death for 24 hours on five control rats and five rats which underwent middle cerebral artery occlusion. Analyses were performed on representative regions of grey, white, and mixed grey/white matter structures. ...

  2. Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats.   Methods: The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay.   Results: The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury.   Conclusions: It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

  3. Restoration of brain protein synthesis in mature and aged rats by a DA agonist, piribedil.

    Science.gov (United States)

    Bustany, P; Trenque, T; Crambes, O; Moulin, M

    1995-01-01

    Brain ageing affects numerous cerebral metabolic pathways such as cerebral glucose consumption or protein synthesis rate. The pharmacological effect of a mixed D1-D2 dopaminergic agonist, piribedil, on this last metabolism is reported. Cerebral Protein Synthesis Rate (CPSR) was measured by the [35S]L-methionine autoradiographic procedure in 38 main brain regions of 11 and 26-month-old Wistar rats after a 2-month treatment per os at 9 and 30 mg/kg/day with piribedil. Mean decrease of CPSR was -21% during the 15-month ageing we followed, with important local variations. Mean CPSR increased with the two treatments, +25% in mature and +35% in aged rats. Treatments restored CPSR of aged rats to the exact mature subjects levels in quite all the brain regions. No dose-effect or asymetrical modification was statistically revealed for the two treatments. Metabolic increases involved particularly central brain gray structures, especially some DA-targeted brain nuclei concerned with behaviour and learning. This effect argued for a general metabotrophic effect of D1-D2 dopamine stimulation of the brain. The original pattern of local ageing of brain protein synthesis in rat was also incidentally reported. This was the first direct report of a wide and effective metabolic activation of CPSR in the brain during ageing by a curative dopaminergic agonist treatment.

  4. Alteration of water-soluble S-100 protein content in microembolized rat brain.

    Directory of Open Access Journals (Sweden)

    Harada,Yasuhiro

    1982-12-01

    Full Text Available The amount of S-100 protein in rat brain embolized with carbon microspheres decreased in parallel with the development of cerebral edema as judged by water content, recovering to the normal range by 24h after embolization. These results suggest the participation of S-100 protein in the permeability characterisitics of nervous system capillaries known as the blood-brain barrier.

  5. Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Daniel J Bonthius

    2007-11-01

    Full Text Available The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region-virus-immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV

  6. Simultaneous MRI and PET imaging of a rat brain

    Science.gov (United States)

    Raylman, Raymond R.; Majewski, Stan; Lemieux, Susan K.; Sendhil Velan, S.; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Zorn, Carl; Marano, Gary D.

    2006-12-01

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  7. Simultaneous MRI and PET imaging of a rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raylman, Raymond R [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Majewski, Stan [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Lemieux, Susan K [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Velan, S Sendhil [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Kross, Brian [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Popov, Vladimir [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Smith, Mark F [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Weisenberger, Andrew G [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Zorn, Carl [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Marano, Gary D [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States)

    2006-12-21

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  8. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  9. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  10. Amphetamine administration improves neurochemical outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dhillon, H S; Dose, J M; Prasad, R M

    1998-09-07

    This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.

  11. Photoacoustic imaging of an inflammatory lesion model in the neonatal rat brain

    Science.gov (United States)

    Guevara, Edgar; Berti, Romain; Londono, Irène; Xie, Ningshi; Bellec, Pierre; Lesage, Frédéric; Lodygensky, G. A.

    2014-09-01

    Periventricular leukomalacia (PVL) is a condition that may cause significant neurodevelopmental handicap in premature newborns. It is characterized by white matter injury, associated with inflammation. This work aimed to assess the impact of inflammation on cerebral oxygen saturation (sO2) using depth-sensitive photoacoustic tomography (PAT). The aspects of PVL were reproduced in a rodent model by injection of lipopolysaccharide (LPS) into the corpus callosum. The results of this exploratory work reveal lower sO2 values in LPS group, as compared to sham controls; showing decreased values in the corpus callosum and in the left cortex, ipsilateral to the injection site. Interhemispherical connectivity was not affected by LPS injection, as shown by functional connectivity analysis. This study supports the use of PAT as a non-invasive tool to assess oxygenation values in vivo in the newborn brain.

  12. Phospholipase A_2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Multiple systemorgan failure is often compli-cated with SAP and PLA2could play an i mportantrole in the study of brain damages.Through thestudy of makingthe rat SAP model inthis study,thesignificance of PLA2on brain damages was surveyedand reported.Materials and methods1 The rat SAP model and its classificationEighty male Sprague-Dawley rats,weight(300±30)g,were randomly divided into4groups:thecontrol group,the sham-operation group,the SAPgroup and the treat ment group of SAP.The ratswere not given food but...

  13. Spontaneous oscillatory burst activity in the piriform-amygdala region and its relation to in vitro respiratory activity in newborn rats.

    Science.gov (United States)

    Onimaru, H; Homma, I

    2007-01-05

    The amygdala is important for the formation of emotions that are affected by olfactory information. The piriform cortex is involved in information processing related to olfaction. To investigate functional interactions between the piriform cortex and amygdala and their relation to medullary respiratory activity, we developed a novel in vitro preparation including the limbic system, brainstem, and spinal cord of newborn rats. With the use of optical and electrophysiologic recordings, we analyzed spontaneous neuronal activity in the piriform-amygdala complex in limbic-brainstem-spinal cord preparations from 0- to 1-day-old rats. For optical recordings, the preparation was stained with a voltage-sensitive dye, and inspiratory activity was monitored from the fourth cervical (C4) ventral root. Spontaneous oscillatory burst activity (up to 10/min) was detected from the rostral cut surface of limbic and para-limbic regions including the piriform cortex and amygdala. The burst activity initially appeared in the piriform cortex and then propagated to the amygdala. We averaged the imaging data in the limbic area with the use of C4 inspiratory activity as a trigger signal. The results suggest functional coupling of the rhythmic burst activity in the piriform-amygdala complex to medullary inspiratory activity, which was confirmed electrophysiologically by cross-correlation analysis of these signals. This rhythmic burst activity may be involved in the development of neuronal circuits that process information related to olfaction, emotion, and respiration.

  14. Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet

    Science.gov (United States)

    Pastuszko, Peter; Schears, Gregory J.; Greeley, William J.; Kubin, Joanna; Wilson, David F.; Pastuszko, Anna

    2014-01-01

    Background Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Material and Methods Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18°C, subjected to 60 min of DHCA, re-warmed and recovered for 8-9 hrs. At the end of experiment, the brains were perfused, fixed and cut into 10 μm transverse sections. Apoptotic cells were visualized by in-situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm2. Results The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46±0.37 to 3.67±1.57 (p=0.002); in the CA1, from 0.11±0.19 to 5.16±1.57 (p=0.001), and in the CA3, from 0.28±0.25 to 2.98±1.82 (p=0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51% and 37%, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. Conclusion In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA. PMID:25082120

  15. Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain.

    Science.gov (United States)

    Arias, B; Arufe, M; Alfonso, M; Duran, R

    1995-04-01

    Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

  16. Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

    Directory of Open Access Journals (Sweden)

    Martin R.

    2015-08-01

    Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

  17. Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; YI-HUA AN; MEI-ZHEN SUN; YA-ZHUO ZHANG; ZHONG-CHENG WANG

    2003-01-01

    To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

  18. Stereological brain volume changes in post-weaned socially isolated rats

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn;

    2010-01-01

    have evaluated the neuroanatomical changes in this animal model in comparison to changes seen in schizophrenia. In this study, we applied stereological volume estimates to evaluate the total brain, the ventricular system, and the pyramidal and granular cell layers of the hippocampus in male and female...... Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

  19. Time-dependent changes in ghrelin-immunoreactivity in dissociated neuronal cultures of the newborn rat neocortex

    NARCIS (Netherlands)

    Stoyanova, Irina I.; Wiertz, Remy W.F.; Rutten, Wim L.C.

    2009-01-01

    Ghrelin is a hormone, initially described as a gastric peptide stimulating appetite and growth hormone secretion, which also has an important role in the regulation of many other processes, including higher brain functions. Ghrelin has been described in situ in different parts of the brain, but so f

  20. Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹; 毛颖; 吴雪海

    2005-01-01

    Objective: To examine the effects of rat marrow stromal cells (rMSCs) on gene expression of local brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after injection of rMSCs into Cistern Magnum of adult rats subjected to traumatic brain injury(TBI).Results: Group cell transplantation had higher BDNF and NGF gene expressions than Group saline control during a period of less than 3 weeks (P<0.05).Conclusions: rMSCs transplantation via Cistern Magnum in rats subjected to traumatic brain injury can enhance expressions of local brain NGF and BDNF to a certain extent.

  1. Age and Heat Stress Related Changes in Monoamine Contents and Cholinesterase Activity in Some Central Nervous System Regions of Albino Rat Newborns

    Directory of Open Access Journals (Sweden)

    M. Bahgat

    2007-01-01

    Full Text Available The normal monoamine [norepinephrine (NE, epinephrine (E, dopamine (DA and serotonin (5-HT] contents and cholinestrase (chE activity were significantly and gradually increased with age progress between postnatal days 7 and 21 in cerebrum, cerebellum, medulla oblongata and spinal cord of rat newborns. The daily exposure of the newborns to 401C for 2 h induced deteriorated effects and the withdrawal period of 7 days failed to return these altered variables to normal levels. On the other hand, the high temperature exerted its most potent decreased effect on monoamine contents at 21 days old. This decrease may be attributed to the elevated activity of monoamine oxidase and/or the decreased activity of the key enzymes responsible for monoamine synthesis. The chE activity exhibited different effects in the tested CNS regions as a result of high temperature exposure; the enzyme activity was decreased markedly at days 7, 14 and 21 in cerebellum and medulla oblongata and lowered only at days 7 and 14 in cerebrum and at day 14 in spinal cord. The subsequent withdrawal for 7 days beyond day 21 produced marked weakening of effect of high temperature exposure on monoamine contents in all examined CNS regions except NE and 5-HT contents in cerebellum and DA level in medulla oblongata. In spite of this attenuation, the values recorded in the withdrawal group were still significantly lower than the normal levels. On the other hand, the chE activity became more deleteriously affected at day 28 in the treated CNS regions except in the medulla oblongata where it was profoundly ameliorated after the withdrawal period.

  2. Age-related changes in reactive oxygen species production in rat brain homogenates.

    Science.gov (United States)

    Driver, A S; Kodavanti, P R; Mundy, W R

    2000-01-01

    The generation of reactive oxygen species (ROS) and resultant oxidative stress have been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases or exposure to environmental chemicals. We have investigated intrinsic age-related differences in the ability of the various brain regions to generate ROS in the absence and presence of Fe(2)+. ROS production in crude brain homogenates from adult rats was linear with respect to time and tissue concentration, and was stimulated to a greater extent by Fe(2)+ than was TBARS production. ROS production was then determined in homogenates from cerebral cortex, striatum, hippocampus, and cerebellum of 7-day-old, 14-day-old, 21-day-old, adult (3-6-month old), and aged (24-month-old) rats using the fluorescent probe 2',7'-dichlorodihydrofluorescin (DCFH). Basal levels of ROS production were similar in 7-, 14-, and 21-day olds, increased in adults, and highest in aged rats, and did not differ between brain regions. ROS production was stimulated by Fe(2)+ (0. 3-30 microM) in a concentration-dependent manner in all brain regions. However, the stimulation of ROS production by Fe(2)+ varied with age. ROS production was greater in 14- and 21-day-old rats compared with adult and aged animals. ROS production in 7-day-old rats was decreased at low Fe(2)+ concentrations and increased at high Fe(2)+ concentrations compared to adult and aged rats. These data show that brain homogenates from neonatal rats respond differently to Fe(2)+, and suggest that developing animals may be more sensitive to oxidative stress in the brain after exposure to toxicants. Published by Elsevier Science Inc.

  3. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  4. Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

    Science.gov (United States)

    Smith, T J; Soderlund, D M

    1998-12-01

    Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

  5. Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation in the rat brain.

    Science.gov (United States)

    Bediz, Cem Seref; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2006-02-01

    Extremely low-frequency (0-300 Hz) electromagnetic fields (EMFs) generated by power lines, wiring and home appliances are ubiquitous in our environment. All populations are now exposed to EMF, and exposure to EMF may pose health risks. Some of the adverse health effects of EMF exposure are lipid peroxidation and cell damage in various tissues. This study has investigated the effects of EMF exposure and zinc administration on lipid peroxidation in the rat brain. Twenty-four male Sprague-Dawley rats were randomly allocated to three groups; they were maintained untreated for 6 months (control, n = 8), exposed to low-frequency (50 Hz) EMF for 5 minutes every other day for 6 months (n = 8), or exposed to EMF and received zinc sulfate daily (3 mg/kg/day) intraperitoneally (n = 8). We measured plasma levels of zinc and thiobarbituric acid reactive substances (TBARS), and levels of reduced glutathione (GSH) in erythrocytes. TBARS and GSH levels were also determined in the brain tissues. TBARS levels in the plasma and brain tissues were higher in EMF-exposed rats with or without zinc supplementation, than those in controls (p < 0.001). In addition, TBARS levels were significantly lower in the zinc-supplemented rats than those in the EMF-exposed rats (p < 0.001). GSH levels were significantly decreased in the brain and erythrocytes of the EMF-exposed rats (p < 0.01), and were highest in the zinc-supplemented rats (p < 0.001). Plasma zinc was significantly lower in the EMF-exposed rats than those in controls (p < 0.001), while it was highest in the zinc-supplemented rats (p < 0.001). The present study suggests that long-term exposure to low-frequency EMF increases lipid peroxidation in the brain, which may be ameliorated by zinc supplementation.

  6. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    Science.gov (United States)

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  7. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  8. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jian-Qin Wang

    2014-01-01

    Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

  9. Effect of manganese on the concentration of amino acids in different regions of the rat brain.

    Science.gov (United States)

    Lipe, G W; Duhart, H; Newport, G D; Slikker, W; Ali, S F

    1999-01-01

    The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains.

  10. Protection of GBE50 on brain mitochondria in rats with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    KaiSUN; GangLIU; Yun-xuanZHANG; Ghen-liangYIN; Gaj-junTIAN; Jia-huPAN

    2005-01-01

    AIM To study the protective effects of the new standardized preparation of Ginkgo biloba extracts(GBE50) anainst brain mitochondrial damages induced by hyperlipemia in rats. METHODS Rat model with hyperlipemia was established by feeding the young male SD rats (3 weeks after born) with high lipid food for 3 months. Then the rats were treated with different dosage of GBE50(ig) for 4 weeks. The prophylaxis rat group were fed with the mixture of high lipid food and GBE50 (50mg/kg/d). The brain mitochondria was separated for determination of the R3, R4 and RCR of the respiration function with the method of Clark's electrode. The mitochondrial transmembrane potential(Δψm) was derected by the Rho123 assay and the cytochrome c release was checked by spectrography. In addition, the parameters of oxidative stress (the activities of SOD, GSH-Px, and the MDA leve) and the activities of ATPase were assayed.

  11. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  12. The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal Newborn Neuron Death After Traumatic Brain Injury.

    Science.gov (United States)

    Chen, Liang; Gao, Xiang; Zhao, Shu; Hu, Weipeng; Chen, Jinhui

    2015-06-01

    Previous studies in rodents have shown that after a moderate traumatic brain injury (TBI) with a controlled cortical impact (CCI) device, the adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus. There is no effective approach for preventing immature neuron death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born immature neurons. We determined that the small molecule imitating BDNF, 7, 8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons both in vitro and in vivo. Pretreatment with DHF protected immature neurons from excitotoxicity-mediated death in vitro, and systemic administration of DHF before moderate CCI injury reduced the death of adult-born immature neurons in the hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These data indicate that DHF may be a promising chemical compound that promotes immature neuron survival after TBI through activation of the BDNF signaling pathway.

  13. Differential antiepileptic effects of the organic calcium antagonists verapamil and flunarizine in neurons of organotypic neocortical explants from newborn rats

    NARCIS (Netherlands)

    Bingmann, D; Speckmann, E J; Baker, R E; Ruijter, J; de Jong, B. M.

    1988-01-01

    Effects of the organic calcium antagonists verapamil and flunarizine on pentylenetetrazol induced paroxysmal depolarizations were tested in organotypic neocortical explants taken from neonatal rats. In these in vitro experiments the papaverin derivative verapamil depressed, and finally abolished, ep

  14. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus.

    Science.gov (United States)

    Ke, Xingrao; McKnight, Robert A; Gracey Maniar, Lia E; Sun, Ying; Callaway, Christopher W; Majnik, Amber; Lane, Robert H; Cohen, Susan S

    2015-07-15

    Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine reprogramming involves the glucocorticoid receptor (GR) gene that is epigenetically regulated in the hippocampus. Using a well-characterized rodent model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR transcription may involve chromatin remodeling of the GR gene. A key chromatin remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1 regulates gene expression by affecting nucleosome repositioning and recruiting transcriptional components to target promoters. We hypothesized that IUGR would increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well as alter nucleosome positioning over GR promoters in newborn male pups. Further, we hypothesized that IUGR would lead to accumulation of specificity protein 1 (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active transcription). Furthermore, the transcription start site of GR exon 1.7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats. Copyright © 2015 the American Physiological Society.

  15. Circumventing the blood-brain barrier: Local delivery of cyclosporin A stimulates stem cells in stroke-injured rat brain.

    Science.gov (United States)

    Tuladhar, Anup; Morshead, Cindi M; Shoichet, Molly S

    2015-10-10

    Drug delivery to the central nervous system is limited by the blood-brain barrier, which can be circumvented by local delivery. In applications of stroke therapy, for example, stimulation of endogenous neural stem/progenitor cells (NSPCs) by cyclosporin A (CsA) is promising. However, current strategies rely on high systemic drug doses to achieve small amounts of CsA in the brain tissue, resulting in systemic toxicity and undesirable global immunosuppression. Herein we describe the efficacy of local CsA delivery to the stroke-injured rat brain using an epi-cortically injected hydrogel composed of hyaluronan and methylcellulose (HAMC). CsA was encapsulated in poly(lactic-co-glycolic acid) microparticles dispersed in HAMC, allowing for its sustained release over 14days in vivo. Tissue penetration was sufficient to provide sustained CsA delivery to the sub-cortical NSPC niche. In comparison to systemic delivery using an osmotic minipump, HAMC achieved higher CsA concentrations in the brain while significantly reducing drug exposure in other organs. HAMC alone was beneficial in the stroke-injured rat brain, significantly reducing the stroke infarct volume relative to untreated stroke-injured controls. The combination of HAMC and local CsA release increased the number of proliferating cells in the lateral ventricles - the NSPC niche in the adult brain. Thus, we demonstrate a superior method of drug delivery to the rat brain that provides dual benefits of tissue protection and endogenous NSPC stimulation after stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  17. Sleep and Newborns

    Science.gov (United States)

    ... 12-Month-Old Bed-Sharing All About Sleep Sleep and Your 1- to 2-Year-Old Communication and Your Newborn Medical Care and Your Newborn Your Newborn's Growth Choosing Safe Baby Products: Cribs Flat Head Syndrome ( ...

  18. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  19. Influence of silver nanoparticles on neurons and blood-brain barrier via subcutaneous injection in rats

    Science.gov (United States)

    Tang, Jinglong; Xiong, Ling; Wang, Shuo; Wang, Jianyu; Liu, Li; Li, Jiage; Wan, Ziyi; Xi, Tingfei

    2008-11-01

    Nanosilver has been widely used in medical biology; however, the distribution and interaction of nanosilver with cells is still unclear. There have been some reports demonstrating that nanoparticles can cross the blood-brain barrier (BBB). The present study investigated the accumulation of silver nanoparticles in the brain, and the effects of silver nanoparticles on BBB. Nanosilver and microsilver (62.8 mg/kg) particles were subcutaneously injected into rats. The rats were sacrificed at predetermined time points and the brains were obtained for ultrastructural observation and silver level detection. The results showed that silver nanoparticles could traverse the BBB and move into the brain in the form of particle. The silver nanoparticles can induce neuronal degeneration and necrosis by accumulating in the brain over a long period of time.

  20. Quantitative autoradiography of (/sup 3/H)corticosterone receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Sapolsky, R.M.; McEwen, B.S. (Rockefeller Univ., New York (USA)); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine)

    1983-07-25

    The authors have quantified corticosterone receptors in rat brain by optical density measurements of tritium-film autoradiograms. Rats were injected i.v. with 500 ..mu..Ci (/sup 3/H)corticosterone to label brain receptors. Frozen sections of brain were cut with a cryostat and exposed for 2 months against tritium-sensitive sheet film (LKB Ultrofilm). Tritium standards were used to convert optical density readings into molar concentrations of receptor. High levels of corticosterone receptors were present throughout the pyramidal and granule cell layers of the hippocampus. Moderate levels of receptors were found in the neuropil of the hippocampus, the lateral septum, the cortical nucleus of the amygdala and the entorhinal cortex. All other brain regions had low levels of receptors. These results extend previous non-quantitative autoradiographic studies of corticosterone receptors and provide a general procedure for the quantitative autoradiography of steroid hormone receptors in brain tissue.

  1. The effects of perinatal protein malnutrition on spatial learning and memory behaviour and brain-derived neurotrophic factor concentration in the brain tissue in young rats.

    Science.gov (United States)

    Wang, Ling; Xu, Ruo-Jun

    2007-01-01

    This study aimed to investigate the effects of perinatal protein malnutrition on brain derived-neurotrophic factor (BDNF) concentration in brain tissue and spatial learning and memory performance in young rats. Nine pregnant Wistar rats were assigned into three groups. Rats in one group were fed with a control diet containing 20% protein. Rats in remaining two groups were fed with a diet containing 6% protein from gestation day eight and day 15 respectively till four weeks after birth. At four weeks of age, the rat pups were evaluated for spatial learning ability using Morris Water Maze (MWM) task. At the end of the behaviour tests, rat pups were sacrificed and the brain tissue samples were collected for measurement of total protein and BDNF concentrations. It was found that rat pups fed the low protein diet had lower body weight and slightly lighter brain compared to the control pups. Total protein levels in hippocampus and cerebral cortex were significantly lower in malnourished pups than the controls. The concentration of BDNF in the hippocampus was also significantly lower in rat pups suffered protein malnutrition from early pregnancy than in the controls. MWM tests showed that perinatal protein deprivation, particularly from early pregnancy, significantly impaired learning and memory ability. The results of the present study indicate that perinatal protein malnutrition had adverse influence on spatial navigation and brain BDNF levels in rats. The decreased hippocampal BDNF concentration might partially contribute to the poor learning memory performance in the protein deprived rats.

  2. Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization.

    Science.gov (United States)

    Bonaccorso, A; Musumeci, T; Serapide, M F; Pellitteri, R; Uchegbu, I F; Puglisi, G

    2017-03-18

    Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan. Physico-chemical and technological characterizations of poly-l-lactide-co-glycolide (negative) and chitosan/poly-l-lactide-co-glycolide (positive) fluorescent labeled nanoparticles were performed. The animals were allocated to three groups receiving negative and positive polymeric nanoparticles via single intranasal administration or no treatment. The localization of both nanocarriers in different brain areas was detected using fluorescent microscopy. Our data revealed that both nanocarriers reach the brain and are able to persist in the brain up to 48h after intranasal administration. Surface charge influenced the involved pathways in their translocation from the nasal cavity to the central nervous system. The positive charge of nanoparticles slows down brain reaching and the trigeminal pathway is involved, while the olfactory pathway may be responsible for the transport of negatively charged nanoparticles, and systemic pathways are not excluded.

  3. Standardized Environmental Enrichment Supports Enhanced Brain Plasticity in Healthy Rats and Prevents Cognitive Impairment in Epileptic Rats

    Science.gov (United States)

    Kouchi, Hayet Y.; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S.; Bezin, Laurent

    2013-01-01

    Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories. PMID:23342033

  4. The expression of Fetuin-A in brain tissues of WAG/Rij Rats, genetic rat model of absence epilepsy

    Directory of Open Access Journals (Sweden)

    Ramazan Yüksel

    2015-12-01

    Full Text Available Objective: In the present study, we aimed to determine the Fetuin-A levels in different regions of the brain in absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats in order to contribute the identification of new potential biomarkers of the diagnosis, prognosis and follow up the epilepsy treatment. Methods: 1, 3 and 6 months old male WAG/Rij rats (n=21 with absence epilepsy were used in this study. All of the rats were decapitated under anesthesia and their cortex and thalamus tissues were isolated. Fetuin-A levels of the groups were determined by Western Blot method by using standard techniques and differences between densities of the groups were compared. Results: According to data obtained, there was no Fetuin-A expression in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy. Conclusion: In this study, it was shown that Fetuin-A is not expressed in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy throughout the age-related development. By evaluating the findings obtained, extensive researches that contain molecular and histological methods must be planned, Fetuin-A findings that are obtained experimentally must be confirmed. J Clin Exp Invest 2015; 6 (4: 387-390

  5. Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

    Directory of Open Access Journals (Sweden)

    Raafat P Fares

    Full Text Available Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage, which offers: (1 minimally stressful social interactions; (2 increased voluntary exercise; (3 multiple entertaining activities; (4 cognitive stimulation (maze exploration, and (5 novelty (maze configuration changed three times a week. The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

  6. Hemodynamic changes of brain in newborns with intracranial hemorrhage%颅内出血新生儿的脑血流动力学变化

    Institute of Scientific and Technical Information of China (English)

    程元平; 刘艳平

    2013-01-01

    Objective To explore the hemodynamic changes in the brains of newborns with intracranial hemorrhage.Methods Totally,61 newborns,born in Anyang Maternal and Child Health Hospital of Henan Province,with intracranial hemorrhage diagnosed by ultrasound in early neonatal period,and 50 healthy newborns,also born in the same hospital from December 1,2010 to June30,2012,were selected.Intracranial hemorrhage newborns were graded according to the severity of hemorrhage and divided into mild (n=45) and severe groups (n =7).The peak systolic flow velocity (Vs),end diastolic velocity (Vd),mean flow velocity (Vm) and resistance index (RI) in the middle cerebral artery (MCA) and anterior cerebral artery (ACA) of brain were measured by Doppler ultrasound.Ttest was applied for statistical analysis.Results Among the 61 neonates with intracranialhemorrhage,12(19.7%) were grade Ⅰ,42(68.9%) were grade Ⅱ,6(9.8%) were grade Ⅲ,and one (1.6%) was grade Ⅳ.The Vs,Vm and Vd of MCA and ACA in the mild and severe intracranial hemorrhage group were significantly lower than those in the control group,the differences were statistically significant [MCA:(55.1±9.1) cm/s,(53.0±6.5) cm/s vs (60.1± 10.3) cm/s;(34.2±6.1) cm/s,(32.5±5.2) cm/s vs (38.2±6.9) cm/s; (17.1±4.8) cm/s,(15.3± 4.0) cm/svs (20.2±5.3) cm/s.ACA:(41.3±11.7) cm/s,(39.4±9.2) cm/s vs (45.3±9.8) cm/s;(25.2±5.8) cm/s,(23.3±4.9) cm/s vs (28.1±5.9) cm/s;(15.0±3.9) cm/s,(13.2±3.1) cm/s vs (15.9±3.8) cm/s,all P<0.05].But the RI values were significantly higher in the control group,the differences were statistically significant (MCA:0.70 ± 0.10,0.77 ± 0.07 vs 0.62 ± 0.10 ; ACA:0.67±0.06,0.73±0.08 vs 0.61±0.05;all P<0.05).TheVs,Vm and Vd of MCA and ACA in the severe intracranial hemorrhage group were significantly lower than in the mild hemorrhage group,while the RI values were significantly higher,and the differences were statistically significant (all P<0.05).Conclusions Newborns with intracranial

  7. Brain activation patterns at exhaustion in rats that differ in inherent exercise capacity.

    Directory of Open Access Journals (Sweden)

    Teresa E Foley

    Full Text Available In order to further understand the genetic basis for variation in inherent (untrained exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively. The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5-15 minutes, 15° slope, 10 m/min or after treadmill running to exhaustion (15-51 minutes, 15° slope, initial velocity 10 m/min. During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines.

  8. Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

    Science.gov (United States)

    Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

    2015-02-01

    Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians.

  9. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  10. Acetaldehyde metabolism by brain mitochondria from UChA and UChB rats.

    Science.gov (United States)

    Quintanilla, M E; Tampier, L

    1995-01-01

    The acetaldehyde (AcH) oxidizing capacity of total brain homogenates from the genetically high-ethanol consumer (UChB) appeared to be greater than that of the low-ethanol consumer (UChA) rats. To gain further information about this strain difference, the activity of aldehyde dehydrogenase (AIDH) in different subcellular fractions of whole brain homogenates from naive UChA and UChB rat strains of both sexes has been studied by measuring the rate of AcH disappearance and by following the reduction of NAD to NADH. The results demonstrated that the higher capacity of brain homogenates from UChB rats to oxidize AcH when compared to UChA ones was because the UChB mitochondrial low Km AIDH exhibits a much greater affinity for NAD than that of the UChA rats, as evidenced by four-to fivefold differences in the Km values for NAD. But the dehydrogenases from both strains exhibited a similar maximum rate at saturating NAD concentrations. Because intact brain mitochondria isolated from UChB rats oxidized AcH at a higher rate than did mitochondria from UChA rats only in state 4, but not in state 3, this strain difference in AIDH activity might be restricted in vivo to NAD disposition.

  11. Probing Intrinsic Resting-State Networks in the Infant Rat Brain

    Science.gov (United States)

    Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

    2016-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

  12. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat.

    Science.gov (United States)

    Pulsinelli, W A; Waldman, S; Rawlinson, D; Plum, F

    1982-11-01

    We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.

  13. Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

    Institute of Scientific and Technical Information of China (English)

    Sung Jin Kwon; Jeongsook Park; So Yun Park; Kwang Seop Song; Sun Tae Jung; So Bong Jung; Ik Ryeul Park; Wan Sung Choi; Sun Ok Kwon

    2013-01-01

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

  14. Brain edema after intracerebral hemorrhage in rats: The role of inflammation

    Directory of Open Access Journals (Sweden)

    Zhang Xiangjian

    2006-01-01

    Full Text Available Background: Intracerebral hemorrhage (ICH results in secondary brain edema and injury that may lead to death and disability. ICH also causes inflammation. It is unclear whether inflammation contributes to brain edema and neuron injury or functions in repairing the brain tissue. Aims: To understand the effect of inflammation in ICH, we have carried out an investigation on the various aspects and the dynamic changes of inflammation. Settings and Design: An ICH model was generated by injecting 50 ml autologous tail artery blood stereotactically into the right caudate nucleus of 30 rats, which were randomly divided into five ICH groups. Similarly, five Sham control groups were generated by inserting the needle to the right caudate nucleus of rats. Materials and Methods: Rat behavior was evaluated over the time course (6 h, 24 h, 48 h, 72 h and 7 d in each group. The rats were then killed by administering an overdose of pentobarbital. Following the euthanasia, the brain water content, neuronal loss, glia proliferation, inflammatory infiltration and brain morphology of the rats were measured. Additionally, the expression of TNF-a,IL-6, ICAM-1, VEGF, NF-kB, C3 and CR2 was analyzed by immunohistochemistry. Statistical Analysis: The data were analyzed by student′s t test. Results: Rat brain water content increased progressively over the time course and reached its peak at 48h followed ICH. The maximum of inflammatory infiltrate (especially neutrophils and immunopositive cells of TNF-a, IL-6 and NF-kB, were at 48h. The expression of C3 and CR2 reached their peaks at 48-72h, while the expression ICAM-1 and VEGF were at maximum at 72h followed ICH. Conclusions: The results suggested that the inflammatory cytokines, complement system and VEGF may have a function in the development of the brain edema and neuron injury followed ICH.

  15. 短暂脑缺血诱导成年大鼠纹状体内CRMP-4的表达%Induction of CRMP-4 in striatum of adult rat after transient brain ischemia

    Institute of Scientific and Technical Information of China (English)

    刘鹏翀; 杨增进; 邱梅红; 张玲妹; 孙凤艳

    2003-01-01

    AIM: To study the expression of collapsing response mediated protein-4 (CRMP-4) and nestin in the ischemic adult rat brain following transient brain ischemia. METHODS: Brain ischemia was induced by transient left middle cerebral artery occlusion (MCAO) for 60 min in adult rats. The expression of CRMP-4, nestin and bromodeoxyuridine (BrdU) was analyzed by immunohistochemical method. The co-localization of CRMP-4 and nestin or BrdU was analyzed by double staining combined with confocal laser scanning microscopy. RESULTS: CRMP-4, a marker of immature neuron, could be expressed in the ipsilateral striatum and cerebral cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of neural stem cell, occurred in above regions from several hours to 2 weeks. CRMP-4 costained with nestin and with BrdU incorporation. CONCLUSION: Neural stem cells may present in the striatum and cerebral cortex of adult rat and can be triggered to differentiate into newborn neuron there by ischemic brain trauma.

  16. Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels.

    Science.gov (United States)

    Wu, Wanqiang; Wang, Xin; Xiang, Qisen; Meng, Xu; Peng, Ye; Du, Na; Liu, Zhigang; Sun, Quancai; Wang, Chan; Liu, Xuebo

    2014-01-01

    Astaxanthin (AST) is a carotenoid pigment which possesses potent antioxidative, anti-inflammatory, and neuroprotective properties. The aim of this study was to investigate whether administration of AST had protective effects on D-galactose-induced brain aging in rats, and further examined its protective mechanisms. The results showed that AST treatment significantly restored the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and increased glutathione (GSH) contents and total antioxidant capacity (T-AOC), but decreased malondialdehyde (MDA), protein carbonylation and 8-hydroxy-2- deoxyguanosine (8-OHdG) levels in the brains of aging rats. Furthermore, AST increased the ratio of Bcl-2/Bax, but decreased the expression of Cyclooxygenase-2 (COX-2) in the brains of aging rats. Additionally, AST ameliorated histopathological changes in the hippocampus and restored brain derived neurotrophic factor (BDNF) levels in both the brains and hippocampus of aging rats. These results suggested that AST could alleviate brain aging, which may be due to attenuating oxidative stress, ameliorating hippocampus damage, and upregulating BDNF expression.

  17. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

    Directory of Open Access Journals (Sweden)

    Bárbara B. Garrido-Suárez

    2015-12-01

    Full Text Available Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX and OVX groups, which were tested for mechanical and thermal hypernociception during 6 weeks and a single acetic acid-induced test 6 weeks after surgery. Redox biomarkers determinations of superoxide dismutase (SOD enzyme activity, glutathione (GSH and nitrates/nitrites as an indicator of nitric oxide (NO concentrations were determined in the brain and cerebellum of 6 animals of each group. Results: Exclusivity OVX rats developed a robust state of mechanical hypernociception and allodynia in the abdomen, hindlimbs and proximal tail. Besides, thermal pain thresholds (hot plate decreased. That was established 3-4 weeks after OVX and lasted for the 6 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX rats. SOD enzyme activity decreased in OVX rats, which showed major deficit for this enzymatic defense under visceral inflammatory injury. However GSH concentrations were increased in brain of OVX animals that allow the balance during acute inflammation. NO concentrations were raised only in OVX rats exposure to chemical inflammatory injury. Conclusions: OVX in rats provide a useful model, which mimics the functional pain in females that could be related with brain oxidative stress.

  18. Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain by oral administration of atorvastatin

    Institute of Scientific and Technical Information of China (English)

    LU Fen; LI Xu; SUO Ai-qin; ZHANG Jie-wen

    2010-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in the elderly. The two hallmark lesions in AD brain are deposition of amyloid plaques and neurofibrillary tangles (NFTs).Hypercholesteremia is one of the risk factors of AD. But its role in the pathogenesis of AD is largely unknown. The aim of this study was to investigate the relationship between hypercholesteremia and tau phosphorylation or β-amyloid (Aβ),and evaluate the effect of atorvastatin on the level of tau phosphorylation and Aβ in the brains of rats fed with high cholesterol diet.Methods Sprague-Dawley (SD) rats were randomly divided into normal diet control group, high cholesterol diet group,and high cholesterol diet plus atorvastatin (Lipitor, 15 mg·kg-1·d-1) treated group. Blood from caudal vein was collected to measure total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3th and the 6th months by an enzymatic method. The animals were sacrificed 6 months later and brains were removed. All left brain hemispheres were fixed for immunohistochemistry. Hippocampus and cerebral cortex were separated from right hemispheres and homogenized separately. Tau phosphorylation and Aβ in the brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau-1) and anti-Aβ40/anti-Aβ42, respectively.Results We found that high cholesterol diet led to hypercholesteremia of rats as well as hyperphosphorylation of tau and increased Aβ level in the brains. Treatment of the high cholesterol diet fed rats with atorvastatin prevented the changes of both tau phosphorylation and Aβ level induced by high cholesterol diet.Conclusions Hypercholesteremia could induce tau hyperphosphorylation and Aβ production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and decrease Aβ generation. It may play a protective role in the patho-process of hypercholesteremia

  19. Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a non-neurotropic epidemic influenza A virus in the newborn/suckling period: implications for influenza-associated encephalopathy.

    Science.gov (United States)

    Yao, Dengfu; Kuwajima, Masamichi; Chen, Ye; Shiota, Mayumi; Okumura, Yuushi; Yamada, Hiroshi; Kido, Hiroshi

    2007-05-01

    The neuropathogenesis of influenza-associated encephalopathy in children and Reye's syndrome remains unclear. A surveillance effort conducted during 2000-2003 in South-West Japan reveals that almost all fatal and handicapped influenza-associated encephalopathy patients exhibit a disorder of mitochondrial beta-oxidation with elevated serum acylcarnitine ratios (C(16:0)+C(18:1))/C(2). Here we show invasion by a non-neurotropic epidemic influenza A H3N2 virus in cerebral capillaries with progressive brain edema after intranasal infection of mice having impaired mitochondrial beta-oxidation congenitally or posteriorly in the newborn/ suckling periods. Mice genetically lacking of carnitine transporter OCTN2, resulting in carnitine deficiency and impaired beta-oxidation, exhibited significant higher virus-genome numbers in the brain, accumulation of virus antigen exclusively in the cerebral capillaries and increased brain vascular permeability compared to in wild type mice. Mini-plasmin, which proteolytically potentiates influenza virus multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries of OCTN2-deficient mice but only a little in wild-type mice. These results suggest that the impaired mitochondrial beta-oxidation changes the susceptibility to a non-neurotropic influenza A virus as to multiplication in the brain capillaries and to cause brain edema. These pathological findings in the brain of mice having impaired mitochondrial beta-oxidation after influenza virus infection may have implications for human influenza-associated encephalopathy.

  20. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  1. Effect of borneol and electroacupuncture on the distribution of hyperforin in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Bin Yu; Ming Ruan; Yong Sun; Xiaobing Cui; Yun Yu; Lingling Wang; Taihui Fang

    2011-01-01

    Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of the blood-brain barrier. As such, the current study examined the distribution of hyperforin in the rat brain, and the effects on the brain distribution of hyperforin of borneol alone (orally administered), and borneol combined with electroacupuncture treatment. High-performance liquid chromatography technology and pharmacokinetic analysis revealed that treatment with borneol alone (300, 600 mg/kg) increased peak concentration and the area under the curve for hyperforin in the brain. In addition, the bioavailability of hyperforin in rat brain increased by 42.7%. However, increasing the dose of borneol dose did not appear to increase the distribution of hyperforin in the brain. Importantly, applying electroacupuncture at Baihui (GV 20) or Yamen (GV 15) appeared to enhance the brain-delivery effects of borneol, although this effect was weak. Overall, our results indicated that borneol alone or combined with electroacupuncture can provide promising strategies for brain-targeted delivery in central nervous system therapy.

  2. Chronic prenatal exposure to the 900 megahertz electromagnetic field induces pyramidal cell loss in the hippocampus of newborn rats.

    Science.gov (United States)

    Bas, O; Odaci, E; Mollaoglu, H; Ucok, K; Kaplan, S

    2009-07-01

    Widespread use of mobile phones which are a major source of electromagnetic fields might affect living organisms. However, there has been no investigation concerning prenatal exposure to electromagnetic fields or their roles in the development of the pyramidal cells of the cornu ammonis in postnatal life. Two groups of pregnant rats, a control group and an experimental group, that were exposed to an electromagnetic field were used. For obtaining electromagnetic field offspring, the pregnant rats were exposed to 900 megahertz electromagnetic fields during the 1-19th gestation days. There were no actions performed on the control group during the same period. The offspring rats were spontaneously delivered--control group (n = 6) and electromagnetic field group (n = 6). Offspring were sacrificed for stereological analyses at the end of the 4th week. Pyramidal cell number in rat cornu ammonis was estimated using the optical fractionator technique. It was found that 900 megahertz of electromagnetic field significantly reduced the total pyramidal cell number in the cornu ammonis of the electromagnetic field group (P electromagnetic field exposure in the prenatal period.

  3. Liver and brain tryptophan metabolism following hydrocortisone administration to rats and gerbils.

    Science.gov (United States)

    Green, A R; Sourkes, T L; Young, S N

    1975-02-01

    1 Liver tryptophan pyrrolase activity is low in the mongolian gerbil (Meriones unguiculatus) and is not induced by hydrocortisone (5 mg/kg). In contrast, there is measurable activity in the rat liver and this is induced by hydrocortisone. In vivo measurements confirmed the absence of induction in gerbils but suggested that they were able to metabolize tryptophan. However no detectable pyrrolase activity was found in any other tissues either before or after hydrocortisone. 2 In agreement with previous observations hydrocortisone decreased rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) 6 h after administration. Brain tryptophan concentrations were also decreased at this time. In contrast, hydrocortisone did not alter gerbil brain 5-HT, 5-HIAA or trytophan. alpha-Methyltryptophan activated hepatic tryptophan pyrrolase and decreased brain 5-HT and 5-HIAA in both animals. 3 Results suggest that the decrease in rat brain 5-HT and 5-HIAA following hydrocortisone may be associated with the rise in liver tryptophan pyrrolase and that the brain amine changes are mediated through the decrease in brain tryptophan concentration.

  4. Metabolism and disposition of 3,6-dibutanoylmorphine in rat brain.

    Science.gov (United States)

    Tasker, R A; Nakatsu, K

    1986-09-01

    In previous studies from this laboratory it was found that dibutanoylmorphine (DBM) was more potent than morphine as an analgesic in rats and that it was less active than acetyl esters of morphine on behaviour. As DBM is a morphine prodrug, the aim of this work was to determine if rat brain homogenates were capable of deacylating DBM and monobutanoylmorphine (MBM) and to determine relative proportions of parent drug to metabolites in the brain in vivo. In 10% (w/v) brain homogenates, DBM was eliminated with a half-life of about 70 min (corrected for dilution), while MBM was eliminated 10 times as quickly. DBM and its metabolites were found in both blood and brain as early as 1 min after i.v. administration of DBM. After 5 min, the predominant form in blood was MBM and in brain it was DBM. Thus, rat brain possesses the capacity to metabolize DBM by deesterification and the parent drug, MBM, and morphine were found in blood and brain in vivo.

  5. MRI relaxation in the presence of fictitious fields correlates with myelin content in normal rat brain.

    Science.gov (United States)

    Hakkarainen, Hanne; Sierra, Alejandra; Mangia, Silvia; Garwood, Michael; Michaeli, Shalom; Gröhn, Olli; Liimatainen, Timo

    2016-01-01

    Brain myelin plays an important role in normal brain function. Demyelination is involved in many degenerative brain diseases, thus quantitative imaging of myelin has been under active investigation. In previous work, we demonstrated the capability of the method known as Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) to provide image contrast between white and gray matter in human and rat brains. Here, we provide evidence pointing to myelin being the major source of this contrast. RAFFn relaxation time constant (TRAFFn) was mapped in rat brain ex vivo. TRAFFn was quantified in 12 different brain areas. TRAFFn values were compared with multiple other MRI metrics (T1, T2 , continuous wave T1ρ, adiabatic T1ρ and T2ρ, magnetization transfer ratio), and with histologic measurements of cell density, myelin and iron content. Highest contrast between white and grey matter was obtained with TRAFFn in the rotating frames of ranks n = 4 and 5. TRAFFn values correlated strongly with myelin content, whereas no associations between TRAFFn and iron content or cell density were found. TRAFFn with n = 4 or 5 provides a high sensitivity for selective myelin mapping in the rat brain. © 2015 Wiley Periodicals, Inc.

  6. Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail: kayo.takahashi@uppsala.imanet.se; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)

    2006-07-15

    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

  7. Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain

    Institute of Scientific and Technical Information of China (English)

    Changzheng Dong; Wenqing Zhao; Wenling Li; Peiyuan Lv; Xiufang Dong

    2013-01-01

    Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors.

  8. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    Science.gov (United States)

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  9. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats

    Institute of Scientific and Technical Information of China (English)

    Erukainure OL; Ajiboye JA; Adejobi RO; Okafor OY; Kosoko SB; Owolabi FO

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Methods:Oxidative stress was induced by oral administration of ethanol (20%w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Results:Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Conclusions:Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.

  10. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  11. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  12. Effects of anesthesia on [11C]raclopride binding in the rat brain

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Simonsen, Mette; Møller, Arne

    Background Very often rats are anesthetized prior to micro positron emission tomography (microPET) brain imaging in order to prevent head movements. Anesthesia can be administered by inhalation agents, such as isoflurane, or injection mixtures, such as fentanyl-fluanisone-midazolam. Unfortunately......, anesthesia affects a variety of physiological variables, including in the brain. Aim The aim of this study was to compare the effects of inhalation and injection anesthesia on the binding potential of the dopaminergic D2/3 tracer [11C]raclopride used for PET brain imaging in human and animal studies....... Materials & Methods Nine male Lew/Mol rats were assigned to either inhalation (isoflurane; N=4) or injection (fentanyl-fluanisone-midazolam; N=5) anesthesia. Catheters were surgically placed in femoral arteries and veins for blood sampling and tracer injection. After a short attenuation scan, the rats were...

  13. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Omar Ortiz-Avila

    2015-01-01

    Full Text Available Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats. Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential ΔΨm, besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  14. DISTRIBUTION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN DIFFERENT PARTS OF THE RAT BRAIN UNDER CADMIUM EXPOSURE.

    Science.gov (United States)

    Kovalchuk, Yu P; Prischepa, I V; Si, U; Nedzvetsky, V S; Kot, Y G; Persky, E E; Ushakova, G A

    2015-01-01

    The chronic effects of low doses of cadmium on the distribution of soluble and filament forms of glial fibrillary acidic protein (GFAP) and their polypeptide fragments in different parts of the rat brain were investigated. Obtained results showed dose-dependent effect of cadmium on the soluble form of GFAP and more pronounced effect on the filament form and composition of the polypeptide fragments of the protein in the rat brain. Prolonged intoxication by cadmium ions in a dose of 1.0 μg/kg of body weight induced a significant decrease in soluble GFAP and an increase in the filament form in the rat brain, pointing to the development of reactive astrogliosis and the risk of neurodegeneration.

  15. Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development.

    Science.gov (United States)

    Ghosh, Payel; Mukherjee, Nabanita; Ghosh, Krishnendu; Mallick, Suvadip; Pal, Chiranjib; Laskar, Aparna; Ghosh, Anirban

    2015-09-01

    The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed.

  16. Effect of Piper betle leaf extract on alcoholic toxicity in the rat brain.

    Science.gov (United States)

    Saravanan, R; Rajendra Prasad, N; Pugalendi, K V

    2003-01-01

    The protective effect of Piper betle, a commonly used masticatory, has been examined in the brain of ethanol-administered Wistar rats. Brain of ethanol-treated rats exhibited increased levels of lipids, lipid peroxidation, and disturbances in antioxidant defense. Subsequent to the experimental induction of toxicity (i.e., the initial period of 30 days), aqueous P. betle extract was simultaneously administered in three different doses (100, 200, and 300 mg kg(-1)) for 30 days along with the daily dose of alcohol. P. betle coadministration resulted in significant reduction of lipid levels (free fatty acids, cholesterol, and phospholipids) and lipid peroxidation markers such as thiobarbituric acid reactive substances and hydroperoxides. Further, antioxidants, like reduced glutathione, vitamin C, vitamin E, superoxide dismutase, catalase, and glutathione peroxidase, were increased in P. betle-coadministered rats. The higher dose of extract (300 mg kg(-1)) was more effective, and these results indicate the neuroprotective effect of P. betle in ethanol-treated rats.

  17. EFFECT OF GINKGO BILOBA EXTRACT ON BRAIN EDEMA AFTER SUBARACHNOID HEMORRHAGE IN RATS

    Institute of Scientific and Technical Information of China (English)

    孙保亮; 夏作理; 杨明峰; 邱平明

    2001-01-01

    @@ The aim of this study was to investigate the protectiveeffect of Ginkgo biloba extract (EGb) on brain edemaafter subarachnoid hemorrhage . Eighty male and femaleWistar rats, weighing 300~ 350g, were used in the ex-periment. Animals were divided into pure SAH group andEGb-treated group. Dynamic changes of regional cerebralblood flow (rCBF) were detected in eight rats from eachgroup. Brain water and electrolytes contents at differenttime points were detected in thirty-two rats from eachgroup (eight rats at each time point from each group) .EGb. provided by Pizhou Pharmaceutical Factory(Xuzhou, Jiangsu, China), was injected intraperi-toneally 30 minutes before operation and repeated withsingle dose of 15mg/kg .every 6 hours.

  18. Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats.

    Science.gov (United States)

    Takahashi, Kenichi; Hayakawa, Chikara; Onimaru, Hiroshi

    2016-04-21

    In the clinical setting, the use of QX-314 (a quaternary derivative of lidocaine) has been proposed to achieve the selective inhibition of nociceptors that express transient receptor potential vanilloid 1 (TRPV1) channels with fewer motor deficits. However, it has been also reported that QX-314 may produce systemic CNS toxicities with relative potencies that are approximately twice as high as those of lidocaine. There are no reports concerning the effects of extracellular QX-314 on the rhythm-generating neurons in the respiratory center. In the present study, we examined the effects of QX-314 on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats. The extracellular application of QX-314 (200μM) decreased the C4 burst rate, amplitude and slope during the initial rising phase, and the effects slowly developed with a half-decay time of approximately 20min. The combined application of capsaicin (10 or 100μM) with QX-314 (100μM) showed no additional effect. The intracellular application of QX-314 (100μM) to respiratory neurons depressed the action potentials with a half-decay time of around 5min. Our findings could explain one of the mechanisms underlying the central toxicities that occur after the systemic application of QX-314.

  19. Effects of Graded Hypothermia on Hypoxic-ischemic Brain Damage in the Neonatal Rat

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

    Objective To investigate the effect of graded hypothermia on neuropathologic alteratiors of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37℃ group, but no death occurred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33℃ (53.3%) and 31℃ groups (44.4%), and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.

  20. Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.

    Directory of Open Access Journals (Sweden)

    Henna Shaikh

    Full Text Available Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns.This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns.Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns.Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns.These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.

  1. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

    OpenAIRE

    Gajendra Kumar; Amita Srivastava; Surinder Kumar Sharma; Yogendra Kumar Gupta

    2014-01-01

    Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behaviou...

  2. Predator Cat Odors Activate Sexual Arousal Pathways in Brains of Toxoplasma gondii Infected Rats

    OpenAIRE

    House, Patrick K.; Ajai Vyas; Robert Sapolsky

    2011-01-01

    Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not infl...

  3. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    OpenAIRE

    Yongjun Jiang; Ning Wei; Juehua Zhu; Tingting Lu; Zhaoyao Chen; Gelin Xu; Xinfeng Liu

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobil...

  4. A Comparison of Psychotomimetic Drug Effects on Rat Brain Norepinephrine Metabolism

    Science.gov (United States)

    1973-02-19

    chemical . Rats remained in the water for a maxi- Indircet evidence for participation of brain cate- mum of 20 minutes, but were removed prior to that...ANI) NOH EPINEPHRINE 45 TABLE 1 Endogenous noresiinephrine content mo rat whole braiin after treatment with various psychoactive drugs or exposure to...conclusion that any differences exist b.-tween these two psychoactive effect of LSD on cerebral norepincphrine metab- drugs with respect to serotonin

  5. Acute stimulation of dissociated cortical neurons of newborn rats with orexin A: Effect on the network activity

    NARCIS (Netherlands)

    Stoyanova, Irina; le Feber, Jakob; Rutten, Wim; El Haj, Alicia; Bader, Dan

    2011-01-01

    Orexin A (OXA) and B are hypothalamic neu-ropeptides with recognized importance in the physiological regulation of various brain activities, including sleep/wakefulness, learning and memory, locomotion, auto-nomic control. Orexin activity is mediated by two types of receptors; OR1 binds OXA with

  6. Acute stimulation of dissociated cortical neurons of newborn rats with orexin A: Effect on the network activity

    NARCIS (Netherlands)

    Stoyanova, I.I.; Feber, le J.; Rutten, W.L.C.; El Haj, Alicia; Bader, Dan

    2011-01-01

    Orexin A (OXA) and B are hypothalamic neu-ropeptides with recognized importance in the physiological regulation of various brain activities, including sleep/wakefulness, learning and memory, locomotion, auto-nomic control. Orexin activity is mediated by two types of receptors; OR1 binds OXA with hig

  7. Element distribution in the brain sections of rats measured by synchrotron radiation X-ray fluorescence

    Science.gov (United States)

    Liu, N. Q.; Zhang, F.; Wang, X. F.; Zhang, Z. Y.; Chai, Z. F.; Huang, Y. Y.; He, W.; Zhao, X. Q.; Zuo, A. J.; Yang, R.

    2004-02-01

    The concentration of trace elements in brain sections was measured by synchrotron radiation X-ray fluorescence. The relative concentration was calculated by means of the normalization of Compton scattering intensity approximately 22 keV, after the normalization for collecting time of X-ray spectrum and the counting of the ion chamber, and subtracting the contribution of the polycarbonate film for supporting sample. Furthermore, the statistical evaluation of the element distribution in various regions of the brain sections of the 20-day-old rats was tested. For investigating the distribution of elements in the brain of iodine deficient rats, Wistar rats were fed with iodine deficient diet and deionized water (ID group). The rats were fed the same iodine deficient diet, but drank KIO 3 solution as control (CT group). The results showed that the contents of calcium (Ca) in thalamus (TH) and copper (Cu) and iron (Fe) in cerebral cortex (CX) of ID rats were significantly lower than that of control rats, while the contents of phosphor (P), sulfur (S), potassium (K), rubidium (Rb), bromine (Br), chlorine (Cl), zinc (Zn), Ca and Cu of ID in hippocampus (H) and the contents of Br, Cl, Zn and Ca in cerebral cortex of ID rats were significantly higher. Especially, the difference of Br, Cl, Zn and Ca in H between ID and CT was more significant. The contents of all elements measured in H were higher than (or equal to) CX and/or TH for both groups, except low Cl of the control rats. Furthermore Zn and Cu contents along the hippocampal fissure in both groups were 1.5 ( Ptimes higher than in hippocampus, respectively. Considering the results of cluster analysis our study shows that the marked alterations in the spatial distribution of Zn and Ca of ID rats brain during brain development stages. In addition, the effect of the perfusion with 0.9% NaCl solution before taking brain on the distribution of elements in the brain sections was observed and discussed.

  8. Macrophagic and microglial responses after focal traumatic brain injury in the female rat

    OpenAIRE

    Turtzo, L. Christine; Lescher, Jacob; Janes, Lindsay; Dean, Dana D.; Budde, Matthew D.; Joseph A Frank

    2014-01-01

    Background After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female ...

  9. Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex.

    Science.gov (United States)

    Schlicker, E; Betz, R; Göthert, M

    1988-05-01

    Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution (containing citalopram, an inhibitor of serotonin uptake) and the effect of histamine on the electrically (3 Hz) evoked 3H overflow was studied. Histamine decreased the evoked overflow in a concentration-dependent manner. The inhibitory effect of histamine was antagonized by impromidine and burimamide, but was not affected by pheniramine, ranitidine, metitepine and phentolamine. Given alone, impromidine facilitated the evoked overflow, whereas burimamide, pheniramine and ranitidine had no effect. The results suggest that histamine inhibits serotonin release in the rat brain cortex via histamine H3 receptors, which may be located presynaptically.

  10. Molecular cloning, expression and in situ hybridization of rat brain glutamic acid decarboxylase messenger RNA.

    Science.gov (United States)

    Julien, J F; Legay, F; Dumas, S; Tappaz, M; Mallet, J

    1987-01-14

    A cDNA library was generated in the expression vector lambda GT11 from rat brain poly(A)+ RNAs and screened with a GAD antiserum. Two clones reacted positively. One of them was shown to express a GAD activity which was specifically trapped on anti-GAD immunogel and was inhibited by gamma-acetylenic-GABA. Blot hybridization analysis of RNAs from rat brain revealed a single 4 kilobases band. Preliminary in situ hybridizations showed numerous cells labelled by the GAD probe such as the Purkinje and stellate cells in the cerebellar cortex and the cells of the reticular thalamic nucleus.

  11. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    DEFF Research Database (Denmark)

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    The effect of partially purified extracts from adult pig brains containing a glia maturation protein factor (BE) has been investigated on neural cells during carcinogenesis. Pregnant BD IX-rats were given a single transplacental dose of the carcinogen ethylnitrosourea (EtNU) on the 18th day of ge...... on GFA-content was seen any longer, although some few weakly GFA positive cells could be observed in all permanent cell lines. Fetal rat brain cells therefore seem to become less responsive to this differentiation inducer during neoplastic transformation in cell culture....

  12. Prevention of brain infarction by postischemic administration of histidine in rats.

    Science.gov (United States)

    Adachi, Naoto; Liu, Keyue; Arai, Tatsuru

    2005-03-28

    Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

  13. Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.

    Science.gov (United States)

    Caccia, S; Carli, M; Garattini, S; Poggesi, E; Rech, R; Samanin, R

    1980-02-01

    Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.

  14. A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.

    Science.gov (United States)

    Haraldseth, O; Jones, R A; Skottner, A

    1997-01-01

    The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.

  15. Brain monoamine metabolism is altered in rats following spontaneous, long-distance running.

    Science.gov (United States)

    Elam, M; Svensson, T H; Thorén, P

    1987-06-01

    Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise.

  16. Dynamic effects of point source electroporation on the rat brain tissue.

    Science.gov (United States)

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, pelectroporation when planning a treatment for brain tumors.

  17. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

    Science.gov (United States)

    Marmarou, A; Foda, M A; van den Brink, W; Campbell, J; Kita, H; Demetriadou, K

    1994-02-01

    This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

  18. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  19. Extremely low frequency magnetic fields induce oxidative stress in rat brain.

    Science.gov (United States)

    Manikonda, Pavan K; Rajendra, Pilankatta; Devendranath, D; Gunasekaran, B; Channakeshava; Aradhya, Shivakumara R S; Sashidhar, Rao B; Subramanyam, Chivukula

    2014-01-01

    The present investigation was conducted to understand the influence of long-term exposure of rats to extremely low frequency magnetic fields (ELF-MF), focusing on oxidative stress (OS) on different regions of rat's brain. Male Wistar rats (21-day-old) were exposed to ELF-MF (50 Hz; 50 and 100 µT) for 90 days continuously; hippocampal, cerebellar and cortical regions from rats were analyzed for (i) reactive oxygen species (ROS), (ii) metabolites indicative of OS and (iii) antioxidant enzymes. In comparison to control group rats, the rats that were continuously exposed to ELF-MF caused OS and altered glutathione (GSH/GSSG) levels in dose-dependent manner in all the regions of the brain. Accumulation of ROS, lipid peroxidation end products and activity of superoxide dismutase in different regions was in the descending order of cerebellum glutathione peroxidase activity were in the descending order of hippocampus 50 µT. Varied influences observed in different regions of the brain, as documented in this study, may contribute to altered metabolic patterns in its related regions of the central nervous system, leading to aberrant neuronal functions.

  20. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...... amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) andALDH1L1 antibody based immunohistochemistry.These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density...

  1. Circulating and Brain BDNF Levels in Stroke Rats. Relevance to Clinical Studies

    OpenAIRE

    Yannick Béjot; Claude Mossiat; Maurice Giroud; Anne Prigent-Tessier; Christine Marie

    2011-01-01

    BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF) levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees o...

  2. Recovery of energy metabolism in rat brain after carbon monoxide hypoxia.

    OpenAIRE

    Brown, S D; Piantadosi, C. A.

    1992-01-01

    Carbon monoxide (CO) may inhibit mitochondrial electron transport in the brain and increase the toxic effects of the gas. This hypothesis was investigated in anesthetized rats during CO exposure and recovery at either normobaric or hyperbaric O2 concentrations. During exposure and recovery, we measured the oxidation level of cerebrocortical cytochrome c oxidase by differential spectroscopy and biochemical metabolites known to reflect aerobic energy provision in the brain. CO exposure (HbCO = ...

  3. Total anesthesia, rats brain surgery, nitric oxide (NO) and free radicals

    OpenAIRE

    Jelenković Ankica V.; Jovanović Marina; Ninković Milica; Maksimović M.; Bošković Bogdan

    2005-01-01

    It is expected that clinical recovery after surgically induced brain trauma is followed by molecular and biochemical restitution. Seven days after surgery, we investigated whether the plastic cannula implanted in the left brain ventricle of adult Wistar rats (n = 6-7), performed in pentobarbital anesthesia, could influence oxidative stress elements (superoxide anion and lipid peroxidation), as well as the antioxidative system (superoxide dismuthase-SOD). Also, we investigated whether nitric o...

  4. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury

    Science.gov (United States)

    Lim, Yi Wei; Meyer, Nathan P.; Shah, Alok S.; Budde, Matthew D.; Stemper, Brian D.; Olsen, Christopher M.

    2015-01-01

    Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure. PMID:25910266

  5. Development of regional cerebral oedema after lateral fluid-percussion brain injury in the rat.

    Science.gov (United States)

    McIntosh, T K; Soares, H; Thomas, M; Cloherty, K

    1990-01-01

    Most studies attempting to characterize post-traumatic oedema formation have focused on the acute postinjury period. We have recently developed a new model of lateral (parasagittal) fluidpercussion (FP) brain injury in the rat. The purpose of the present study was to characterize the temporal course of oedema formation and resolution in this experimental model of brain injury. Male Sprague-Dawley rats (n = 67) were anaesthetized and subjected to FP brain injury of moderate severity. Animals were sacrified at 1 hour, 6 hours, 24 hours, 2 days, 3 days, 5 days and 7 days after brain injury, brains removed and assayed for water content using either specific gravitimetric or wet weight/dry weight techniques. In the injured left parietal cortex, a significant increase in water content was observed by 6 hours postinjury (p less than 0.05) that persisted up to 5 days postinjury. A prolonged and significant increase in water content was also observed in the left (ipsilateral) hippocampus which began at 1 hour postinjury (p less than 0.05) and continued up to 3 days. Other regions examined showed no significant regional oedema after brain injury. These results suggest that lateral FP brain injury produces an early focus oedema that persists for a prolonged period after trauma. This model may be useful in the evaluation of novel pharmacological therapies designed to reduce cerebral oedema after brain injury.

  6. Effects of white spirits on rat brain 5-HT receptor functions and synaptic remodeling

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Plenge, P.; Jørgensen, O.S.

    2001-01-01

    Previously, inhalation exposure to different types of white spirit (i.e. complex mixtures of aliphatic, aromatic, alkyl aromatic, and naphthenic hydrocarbons) has been shown to induce neurochemical effects in rat brains. Especially, the serotonergic system was involved at the global, regional...... applied as indices for synaptic remodeling in forebrain, hippocampus, and entorhinal cortex. Male Wistar rats were exposed to 0, 400, or 800 ppm of aromatic (20 vol.% aromatic hydrocarbons) or dearomatized white spirit (catalytically hydrogenated white spirit) in the inhaled air for 6 h/day, 7 days...... that inhalation exposure to high concentrations of white spirit may be neurotoxic to rats, especially the aromatic white spirit type....

  7. Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xiangjian Zhang; Li Xü; Zuoran Chen; Shuchao Hu; Liying Zhang; Haiyan Li; Ruichun Liu

    2008-01-01

    BACKGROUND: Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury.OBJECTIVE: To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B (κ B), interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia.DESIGN, TIME AND SETTING: The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIAIS: A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320 g, were selected. Naoxintong powder (mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis) was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608.METHODS: The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 glkg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage. All rats were administered by garage at 5 and 23 hours following surgery, and subsequently, once per day.MAIN OUTCOME MEASURES: At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- κB, interleukin-6, tumor necrosis factor-α, and complement 3 was examined by immunohistochemistry.RESULTS: A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as

  8. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  9. Fenbendazole treatment may influence lipopolysaccharide effects in rat brain.

    Science.gov (United States)

    Hunter, Randy L; Choi, Dong-Young; Kincer, Jeanie F; Cass, Wayne A; Bing, Guoying; Gash, Don M

    2007-10-01

    In evaluating discrepant results between experiments in our laboratory, we collected data that challenge the notion that anthelminthic drugs like FBZ do not alter inflammatory responses. We found that FBZ significantly modulates inflammation in F344 rats intrastriatally injected with LPS. FBZ treatment of LPS-injected rats significantly increased weight loss, microglial activation, and dopamine loss; in addition, FBZ attenuated the LPS-induced loss of astrocytes. Therefore, FBZ treatment altered the effects of LPS injection. Caution should be used in interpreting data collected from rats treated with LPS and FBZ.

  10. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  11. Effects of anesthesia on [11C]raclopride binding in the rat brain

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Simonsen, Mette; Møller, Arne

    Background Very often rats are anesthetized prior to micro positron emission tomography (microPET) brain imaging in order to prevent head movements. Anesthesia can be administered by inhalation agents, such as isoflurane, or injection mixtures, such as fentanyl-fluanisone-midazolam. Unfortunately....... Materials & Methods Nine male Lew/Mol rats were assigned to either inhalation (isoflurane; N=4) or injection (fentanyl-fluanisone-midazolam; N=5) anesthesia. Catheters were surgically placed in femoral arteries and veins for blood sampling and tracer injection. After a short attenuation scan, the rats were...... PET scanned for 90 minutes after injection of [11C]raclopride. Results We found that rats anesthetized with isoflurane had double the binding potential in the striatum compared with fentanyl-fluanisone-midazolam anesthetized rats. Conclusion Our results are in agreement with other studies showing...

  12. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  13. Zinc influences on brain development, pituitary an thyroidfunction iniodine-deficient pregnant and neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Xiaoxia Yang; Jianchao Bian; Xin Wang; Haiming Wang; Yongping Liu; Shuzhen Wang; Zhichun Mu; Xinluan Li

    2008-01-01

    BACKGROUND: Zinc (Zn) has been shown to greatly influence brain development. Zn supplements may reduce injury to cell membranes of the thyroid gland due to iodine deficiency. OBJECTIVE: To establish an iodine deficiency rat model using low-iodine food, which was supplemented with compound Zn and Zn gluconate, to observe the effects of Zn on brain development, as well as pituitary gland and thyroid gland function in iodine-deficient rats. DESIGN, TIME AND SETTING: Randomized grouping study of neural development was performed in the central laboratory of Shandong Institute for Prevention and Treatment of Endemic Disease from 1998 to 1999. MATERIALS: A total of 270 Wistar, female rats, one month after weaning, were used in this study, including 150 pregnant and 120 neonatal rats. Rats were randomly divided into six groups: normal control, model, iodine, compound Zn, iodine and compound Zn, and zinc gluconate. Each group contained 25 pregnant rats and 20 nenoatal rats. METHODS: The pregnant rats and 20 neonatal rats, and well as the normal group, were fed standard chow and allowed free access to tap water (containing 5 μ g/L iodine and 1 mg/L Zn). The remaining five groups were fed low-iodine chow. However, the model group received distilled water, the iodine group received potassium-iodide distilled water (containing 300 μ g/L iodine), the compound Zn group received distilled water and intragastrically administrated 10 mL/kg compound Zn solution, once per day, the iodine and compound Zn group received distilled water with 300 p g/L iodine and intragastrically administrated 10 mL/kg compound Zn solution, once per day. All treatments lasted 90 days. MAIN OUTCOME MEASURES: All pregnant rats were sacrificed on the day 21 of pregnancy. Body mass, number and rate of fetal absorption, as well as fetal death and malformation, were determined. Thyroid and pituitary gland weights were measured, as well as serum levels of thyroid hormone, gonadotropin, and sex hormones. In the

  14. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  15. A warmer ambient temperature increases the passage of interleukin-1β into the brains of old rats

    Science.gov (United States)

    Buchanan, Jessica B.; Peloso, Elizabeth; Satinoff, Evelyn

    2008-01-01

    We have demonstrated that after intraperitoneal lipopolysaccharide (LPS) injection, old rats mount fevers similar to those of young rats at an ambient temperature (Ta) of 31°C, but not at 21°C. The same is true for intraperitoneal or intravenous IL-1β administration. The underlying mechanism responsible for blunted fever in old rats may be a deficiency in communication between the periphery and the brain. Possibly, peripheral cytokine actions are altered in old rats, such that the signal that reaches the brain is diminished. Here, we hypothesized that at standard laboratory temperatures, not enough IL-1β is reaching the brain for fever to occur and that a warmer Ta would increase the influx of IL-1β into the brain, enabling old rats to generate fever. Young (3–5 mo) and old (23–29 mo) Long-Evans rats were maintained for 3 days at either Ta 21 or 31°C prior to intravenous injection with radiolabeled IL-1β to measure passage across the blood-brain barrier. Young rats showed similar influx of IL-1β into the brain at the two Tas, but old rats showed significant influx only at the warmer Ta. These data suggest that the lack of fever at a cool Ta may be due to a reduced influx of IL-1β into the brain. PMID:18448612

  16. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel [Center for Radiotherapy Research, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Québec J1H 5N4 (Canada); Masson-Côté, Laurence; Guillot, Mathieu, E-mail: mathieu.guillot@usherbrooke.ca [Department of Radiation Oncology, Centre Hospitalier Universitaire de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada and Center for Radiotherapy Research, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Québec J1H 5N4 (Canada)

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  17. Functional brain activation during retrieval of visceral pain-conditioned passive avoidance in the rat.

    Science.gov (United States)

    Wang, Zhuo; Bradesi, Sylvie; Charles, Jonathan R; Pang, Raina D; Maarek, Jean-Michel I; Mayer, Emeran A; Holschneider, Daniel P

    2011-12-01

    This study assessed functional brain activation in rats during expectation of visceral pain. Male rats were trained in step-down passive avoidance (PA) for 2 days. Upon stepping down from a platform, conditioned animals received noxious colorectal distension delivered through a colorectal balloon, whereas the balloon in control rats remained uninflated. On day 3, PA behavior was assessed while [(14)C]-iodoantipyrine was infused intravenously, followed by immediate euthanasia. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed by statistical parametric mapping using 3-dimensional brains reconstructed from autoradiographic brain slice images. Associated with retrieved PA behavior, conditioned rats compared with control subjects showed increases in rCBF in sensory (anterior insula, somatosensory cortex), limbic/paralimbic regions (anterior cingulate, prelimbic cortex, amygdala), all regions previously reported to show activation during acute visceral pain. Increases in rCBF were also noted in the dorsal hippocampus, nucleus accumbens, and caudate putamen, regions associated with retrieval of PA. Organization of the underlying brain network was further delineated by functional connectivity analysis. This revealed in conditioned rats a strongly and positively connected corticostriatal cluster (cingulate, prelimbic cortex, caudate putamen). The amygdala and cerebellar hemispheres formed another positively connected cluster, which was negatively connected with the corticostriatal cluster, suggesting corticolimbic modulation. Prelimbic cortex, nucleus accumbens, and anterior insula emerged in conditioned animals as hubs. Our results show that during retrieval of PA, brain areas implicated in PA expression as well as those implicated in acute visceral pain processing were recruited, in line with findings from human brain imaging studies on pain expectation. Copyright © 2011 International Association for the Study of Pain. All rights reserved.

  18. Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Jinting He; Weidong Yu; Lingling Hou; Jiajun Chen

    2012-01-01

    A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

  19. Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    GAO Yang; DING Xin-sheng; XU Shu; WANG Wei; ZUO Qi-long; KUAI Feng

    2009-01-01

    Background The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood,but the system of reactive oxygen superoxide (ROS) might be involved.Edaravone (MC1-186),a potent free radical scavenger that prevents apoptosis of neurons,was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.Methods One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups:group 1,control rats receiving sham operation only;group 2,rats with SAH treated by saline;group 3,rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally;and group 4,rats with SAH treated with 3 mg/kg MC1-186.Treated with either saline or MC1-186 twice daily for two consecutive days after SAH,the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining.In addition,mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group.One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.Results The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality,and were found to have significantly increased levels of MDA and caspase-3,but reduced SOD activities in brain tissues (P<0.05).When treated with MC1-186 at two different dosages,the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P<0.05),along with improved scores of neurological evaluation (P<0.05).Conclusions This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MC1-186,a radical scavenger,can efficiently diminish apoptosis of neurons and thus prevent the function

  20. Brain catecholamines in spontaneously hypertensive and DOCA-salt hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Fujino,Kazuyuki

    1984-08-01

    Full Text Available The concentrations and alpha-methyl-p-tyrosine (alpha-MPT induced disappearance of catecholamines, adrenaline, noradrenaline and dopamine, were measured in selected areas of the brainstem and hypothalamus of spontaneously hypertensive rats (SHR and deoxycorticosterone acetate (DOCA-salt hypertensive rats. The catecholamine levels were measured by a sensitive radioenzymatic assay method combined with microdissection of the rat brain. The adrenaline concentration was higher in the area A1 of young SHR, but not in adult SHR, than in age-matched control rats. Noradrenaline concentrations and the alpha-MPT induced noradrenaline disappearance were less in the rostral part of the nucleus tractus solitarii (NTS and the nucleus hypothalamic anterior of young SHR, and in the rostral part of the NTS of adult SHR. On the other hand in DOCA-salt hypertensive rats, the concentrations of adrenaline and noradrenaline were the same as in control rats in the examined areas. The alpha-MPT induced noradrenaline disappearance was less in the rostral part of the NTS of DOCA-salt hypertensive rats. Dopamine concentrations and the alpha-MPT induced dopamine disappearance were the same in the examined areas of SHR and DOCA-salt hypertensive rats. The results suggest that SHR have a change in adrenergic neural activity in the brainstem and a decrease in noradrenergic neural activity in the brainstem and hypothalamus while DOCA-salt hypertensive rats have a decrease in noradrenergic neural activity in the brainstem. Such changes in brain catecholaminergic neurons may have played an important role in the development of hypertension in these rats.

  1. The diffusion permeability to water of the rat blood-brain barrier

    DEFF Research Database (Denmark)

    Bolwig, T G; Lassen, N A

    1975-01-01

    The diffusion permeability to water of the rat blood-brain-barrier (BBB) was studied. Preliminary data obtained with the Oldendorf tissue uptake method (Oldendorf 1970) in seizure experiments suggested that the transfer from blood to brain of labelled water is diffusion-limited. More definite evi...... passage increased from 0.26 to 0.67 when the arterial carbon dioxide tension was changed from 15 to 85 mm Hg, a change increasing the cerebral blood flow about sixfold. This finding suggests that water does not pass the blood-brain barrier as freely as lipophilic gases....

  2. Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

    Directory of Open Access Journals (Sweden)

    Yannick Béjot

    Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

  3. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    Energy Technology Data Exchange (ETDEWEB)

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  4. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    Directory of Open Access Journals (Sweden)

    Hamze Badeli

    2016-09-01

    Full Text Available Objective: Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP, and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE on the aforementioned parameters. Materials and Methods: In this experimental study, diffused traumatic brain injury (TBI was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days, vehicle (distilled water, for 14 days and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results: Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion: ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI.

  5. Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

    Directory of Open Access Journals (Sweden)

    Rafael Simas

    2012-01-01

    Full Text Available OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage

  6. Phospholipase A2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yao Xuan; Chen Xi; Ji Zongzheng

    2007-01-01

    Objective To survey changes and the significance of phospholipase A2(PLA2) on brain tissue of SD rat in acute pancreatitis. Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct, rat model of severe acute pancreatitis (SAP) was made,and it included four groups: the control group, the sham-operation group, the SAP group and the PLA2 inhibitor-treated group of SAP. Serum amylases, PLA2 and PLA2 in brain tissue were measured and the brain tissue changes were observed. Results There were no significant difference in serum amylases, PLA2 and PLA2 in brain tissue between the sham-operation and the control groups; the levels of serum amylases, PLA2 and PLA2 in brain tissue in the SAP group were higher than those in the control. In the SAP group expansion and hemorrhage of meninges, intracephalic arteriolar hyperemia, in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed, significant differences were found between two groups.Compared with the SAP group, the level of serum amylase, PLA2 and PLA2 in brain tissue were reduced significantly in the treatment group of SAP. Pathological damages in the treatment group were significantly reduced when compared with the SAP group. Conclusion PLA2 might play an important role in brain tissue damages in severe acute pancreatitis.

  7. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.

    Science.gov (United States)

    Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Liu, Zhen; Masoodi, Mojgan; Bazinet, Richard P

    2013-09-01

    Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.

  8. 65zinc uptake from blood into brain and other tissues in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. (Sunderland Polytechnic, Tyne Wear (England))

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  9. L-DEPRENYL REDUCES BRAIN-DAMAGE IN RATS EXPOSED TO TRANSIENT HYPOXIA-ISCHEMIA

    NARCIS (Netherlands)

    KNOLLEMA, S; AUKEMA, W; HOM, H; KORF, J; TERHORST, GJ

    1995-01-01

    Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. Metho

  10. Brain-specific modulation of kynurenic acid synthesis in the rat

    DEFF Research Database (Denmark)

    Gramsbergen, J B; Hodgkins, P S; Rassoulpour, A;

    1997-01-01

    This study was designed to investigate modulatory mechanisms that control the synthesis of the neuroprotective endogenous excitatory amino acid receptor antagonist kynurenate. De novo kynurenate formation was examined in vitro using tissue slices from rat brain, liver, and kidney. In slices from ...

  11. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  12. Inhibition of acetylcholinesterase and different ATPases by a novel phosphorothionate (RPR-II) in rat brain.

    Science.gov (United States)

    Rahman, M F; Siddiqui, M K; Jamil, K

    2000-10-01

    A novel phosphorothionate (2-butenoic acid-3-(diethoxy phosphinothioyl)-methyl ester (RPR-II), synthesized at the Indian Institute of Chemical Technology, Hyderabad, targets its effect on rat brain acetylcholinesterase (AChE) and Na(+)-K(+), Mg(2+), and Ca(2+) ATPases, as evident in this investigation. Three subchronic doses 0.014 (low), 0.028 (medium), and 0.042 (high) mg kg(-1) were administered to rats daily for a period of 90 days RPR-II caused statistically significant dose- and time-dependent inhibition in brain AChE and also in Na(+)-K(+), Mg(2+), and Ca(2+) ATPases in both male and female rats after 45 and 90 days of treatment. The low dose was generally insignificant while the medium and high doses were significantly effective. Females were more susceptible than males with regard to brain AChE, Na(+)-K(+), and Mg(2+) ATPases, which indicates sexual dimorphism in the treated rats. Interestingly, after 28 days post-treatment, recovery of these enzymes was observed. The relative sensitivities of these enzymes indicated that brain AChE was more sensitive than any of the ATPases, but among the ATPases Na(+)-K(+) ATPase was more susceptible than Ca(2+) or Mg(2+) ATPases. This compound, besides inhibiting the target of organophosphates, AChE, also inhibited different ATPases, suggesting both synaptic transmission and nerve conduction were affected.

  13. Differential distribution of calcineurin Aα isoenzyme mRNA's in rat brain

    NARCIS (Netherlands)

    Buttini, M.; Limonta, S.; Luyten, M.; Boddeke, H.

    1993-01-01

    Specific antisense oligonucleotide probes for the α isoforms of the catalytic subunit (A-subunit) of calcineurin were prepared and the distribution of Aα1 and Aα2 mRNA's has been studied in rat brain using in situ hybridization histochemistry. Clear regional differences have been observed for the Aα

  14. Local oxytocin expression and oxytocin receptor binding in the male rat brain is associated with aggressiveness

    NARCIS (Netherlands)

    Calcagnoli, Federica; de Boer, Sietse F.; Beiderbeck, Daniela I.; Althaus, Monika; Koolhaas, Jaap M.; Neumann, Inga D.

    2014-01-01

    We recently demonstrated in male wild-type Groningen rats that enhancing brain oxytocin (OXT) levels acutely produces marked pro-social explorative and anti-aggressive effects. Moreover, these pharmacologically-induced changes are moderated by the individual's aggressive phenotype, suggesting an inv

  15. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  16. Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain

    DEFF Research Database (Denmark)

    Verma, A; Hirsch, D J; Hanley, M R

    1990-01-01

    ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 mi...

  17. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    Directory of Open Access Journals (Sweden)

    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  18. The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

    Science.gov (United States)

    The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

  19. Dragon's blood may have radioprotective effects in radiation-induced rat brain injury.

    Science.gov (United States)

    Xin, Nian; Li, Yu-Juan; Li, Xu; Wang, Xiao; Li, Yan; Zhang, Xiao; Dai, Rong-Ji; Meng, Wei-Wei; Wang, Hai-Long; Ma, Hong; Schläppi, Michael; Deng, Yu-Lin

    2012-07-01

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis. It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon (12)C(6+) heavy ions or (60)Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the "irradiation only" control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats (P Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels (P Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 (P Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins (P Dragon's blood has radioprotective properties in rat brains after both heavy ions and (60)Co γ-ray exposure.

  20. Regional localization of halopemide, a new psychotropic agent, in the rat brain

    NARCIS (Netherlands)

    Loonen, A.J.M.; Van Wijngaarden, I.; Janssen, P.A.J.; Soudijn, W.

    1978-01-01

    Halopemide is a new psychotropic agent, structurally related to the neuroleptics of the butyrophenone type, but with a different pharmacological and clinical profile. The concentration of halopemide in the rat brain is about 10 times less than that of R 29800, its chemical congener and of spiperone,

  1. Steroid Anti-Inflammatory Effects Did Not Improve Organ Quality in Brain-Dead Rats

    NARCIS (Netherlands)

    Rebolledo, Rolando A.; Liu, Bo; Akhtar, Mohammed Z.; Ottens, Petra J.; Zhang, Jian-ning; Ploeg, Rutger J.; Leuvenink, Henri G. D.

    2015-01-01

    Effect of glucocorticoid administration on improving the outcomes of kidney and liver allografts has not been clearly elucidated. This study investigated the effect of prednisolone administration after onset of brain death (BD) on kidney and liver in a controlled rat model of BD. BD was induced in

  2. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.;

    2000-01-01

    of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat......N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...

  3. Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat

    NARCIS (Netherlands)

    Van Dijk, G; Seeley, RJ; Thiele, TE; Friedman, MI; Ji, H; Wilkinson, CW; Burn, P; Campfield, LA; Tenenbaum, R; Baskin, DG; Woods, SC; Schwartz, MW; Seeley, Randy J.; Thiele, Todd E.; Friedman, Mark I.; Wilkinson, Charles W.; Baskin, Denis G.; Woods, Stephen C.; Schwartz, Michael W.

    To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 mu g) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to

  4. The rate of training response to aerobic exercise affects brain function of rats.

    Science.gov (United States)

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.

  5. The influence of microwave radiation from cellular phone on fetal rat brain.

    Science.gov (United States)

    Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

    2012-03-01

    The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (Pcellular phones during pregnancy has certain harm on fetal rat brains.

  6. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    Science.gov (United States)

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.

  7. Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Hui Zhu; Xiao Han; Dafeng Ji; Guangming Lv; Meiyu Xu

    2012-01-01

    Sprague-Dawley neonatal rats within 7 days after birth wer