International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
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Int. J. Dev. Neurosci. · Jun 2010
d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum.
The present work investigated the effects of intrastriatal administration of d-serine on relevant parameters of oxidative stress in striatum of young rats. d-Serine significantly induced lipid peroxidation, reflected by the significant increase of thiobarbituric acid-reactive substances, and significantly diminished the striatum antioxidant defenses, as verified by a decrease of the levels of reduced glutathione and total antioxidant status. Finally, d-serine inhibited superoxide dismutase activity, without altering the activities of glutathione peroxidase and catalase. ⋯ The present data indicate that d-serine in vivo administration induces lipid oxidative damage and decreases the antioxidant defenses in the striatum of young rats. Therefore, it is presumed that this oxidative stress may be a pathomechanism involved at least in part in the neurological damage found in patients affected by disorders in which d-serine metabolism is compromised, leading to altered concentrations of this d-amino acid.
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Int. J. Dev. Neurosci. · Apr 2010
The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine.
Bile duct ligation (BDL) in developing rats causes cholestasis, impaired liver function and cognition. Because both nitric oxide (NO) and ammonia are implicated in hepatic encephalopathy (HE), we hypothesized that asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and ammonia affect cognition in young rats with BDL. Four groups of young male Sprague-Dawley rats ages 17 days were used: rat underwent laparotomy (SC group), rat underwent laparotomy plus a 30% ammonium acetate diet (SC+HA group), rat underwent BDL (BDL group), rats underwent BDL plus high ammonia diet (BDL+HA group). ⋯ High ammonia diet increased plasma ammonia and ADMA concentration, and aggravated spatial deficit in the presence of BDL-induced cholestasis. We conclude plasma ADMA plays a role in BDL-induced spatial deficit. High ammonia aggravated the spatial deficits encountered in cholestatic young rats.
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Int. J. Dev. Neurosci. · Nov 2009
Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain.
Ketamine, a widely used pediatric anesthetic, has been associated with enhanced neuronal toxicity in the developing brain, but mechanisms and neuronal susceptibility to neurotoxic insult leading to neuronal cell death remain poorly defined. One of the main goals of this study was to determine whether there is a duration of ketamine-induced anesthesia below which no significant ketamine-induced neurodegeneration can be detected. Newborn rhesus monkeys (postnatal day 5 or 6) were administered ketamine intravenously for 3, 9 or 24h to maintain a steady anesthetic plane, followed by a 6-h withdrawal period. ⋯ These data show that treatment with ketamine up to 3h is without adverse effects as determined by nerve cell death. However, anesthetic durations of 9h or greater are associated with significant brain cell death in the frontal cortex. Thus, the threshold duration below which no neurotoxicity would be expected is somewhere between 3 and 9h.
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Int. J. Dev. Neurosci. · Oct 2009
Late measures of microstructural alterations in severe neonatal hypoxic-ischemic encephalopathy by MR diffusion tensor imaging.
Neonatal hypoxic-ischemic encephalopathy is a major cause of brain damage in infants, and is associated with periventricular white matter injury and chronic neurological dysfunctions. However, the mechanisms of the chronic white matter injury and reorganization are still unclear. In this study, in vivo diffusion tensor imaging (DTI) was employed to evaluate the late changes of white matter microstructural integrity in the rat brains at 10 weeks after severe neonatal hypoxic-ischemic insults at postnatal day 7. ⋯ A significantly lower fractional anisotropy but higher axial and radial diffusivities and trace were also found in the ipsilateral corpus callosum, proximal external capsule and anterior commissure, while slightly lower fractional anisotropy and axial diffusivity were noticed in the ipsilateral internal capsule and optic nerve. It was suggested that increased fractional anisotropy, axial diffusivity and trace characterize white matter reorganization in chronic neonatal hypoxic-ischemic insults, whereas reduction in fractional anisotropy appears to characterize two types of white matter lesions, with significantly higher axial and radial diffusivities and trace being primary and slightly lower axial diffusivity being secondary. Combined with fractional anisotropy directionality map, in vivo DTI provides important indices to differentiate the chronic effects of severe neonatal hypoxic-ischemic injury and recovery globally, quantitatively and non-invasively.
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Int. J. Dev. Neurosci. · Apr 2009
Developmental exposure to methylmercury elicits early cell death in the cerebral cortex and long-term memory deficits in the rat.
Experiments were performed to assess the neurotoxic effects induced by prenatal acute treatment with methylmercury on cortical neurons. To this purpose, primary neuronal cultures were obtained from cerebral cortex of neonatal rats born to dams treated with methylmercury (4 and 8 mg/kg by gavage) on gestational day 15, the developmental stage critical for cortical neuron proliferation. Prenatal exposure to methylmercury 8 mg/kg significantly reduced cell viability and caused either apoptotic or necrotic neuronal death. ⋯ This exposure level eliciting apoptotic death did not result in cognitive dysfunctions. In conclusion, the methylmercury-induced disruption of glutamate pathway during critical windows of brain development may interfere with cell fate and proliferation resulting in a more or less severe cortical lesions associated or not with loss of function later in life, depending on the exposure levels. Therefore, the early biochemical effects and long-term behavioral changes elicited by high methylmercury levels suggest that the developing brain is impaired in its ability to recover following toxic insult, and the initial effects on cortical neurons may lead to permanent cognitive dysfunctions.