J W Olney

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..In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested...

..Recent findings shed new light on this issue, especially with respect to in vivo apoptosis, and views that are contrary to prevailing interpretations are expressed, especially in the burgeoning apoptosis field of inquiry...

..Many other chemicals in the human environment remain to be evaluated for their ability to cause developing CNS neurons to commit suicide, and this provides an exciting challenge for the field of developmental neurotoxicology...

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..The cell death process evolved relatively slowly and was still ongoing 7 days posttreatment. Relevance of these results to AD is discussed...

..In this study we found that ketamine has this same age and sex dependency profile, and N(2)O has the same age but not sex dependency. Male and female rats are equally sensitive to N(2)O neurotoxicity...

..Here we show that two GABAmimetic anesthetic agents--propofol and sodium thiopental--protect against the irreversible neurodegenerative reaction induced by the powerful NMDA antagonist, MK-801...

..Therefore, it appears that ethanol-induced neuroapoptosis is an intrinsic pathway-mediated phenomenon involving Bax-induced disruption of mitochondrial membranes and cytochrome c release as early events leading to caspase-3 activation...

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..This vulnerability may be related to the physiological role of glucocorticoids in regulating programmed cell death in the mammalian cerebellum...

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..This paper summarizes the use of isolated retina as a model system for studies of excitotoxicity from a theoretical and methodological point of view, and reviews results obtained from studies utilizing this system...

..These data strongly suggest a role for T channels in peripheral nociception. Redox sites on T channels in peripheral nociceptors could be important targets for agents that modify pain perception...

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..Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor...

..Our findings suggest that apoE4 expression in the brain may have selective deleterious effects on memory function in the absence of typical Alzheimer's-like neuropathology...

..Understanding the molecular properties of this receptor will be important for understanding both physiological GABA neurotransmission and the pathology of GABA receptor overactivation...

..We conclude that relatively mild exposure to ketamine, midazolam or a combination of these drugs can trigger apoptotic neurodegeneration in the developing mouse brain...

..Since blood ethanol elevations in this range are commonly achieved by humans in a social drinking context, a mother with only a moderate drinking habit might expose her fetus to such elevations on multiple occasions during pregnancy...

..We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment...

..These results show that glutamatergic neurotransmission persistently adapts to changes in electrical activity over a wide physiological range...

..We conclude that absence of functional caspase-3 alters the time course and morphological characteristics of the neurodegenerative process but does not prevent ethanol-induced neuron death...

..Prevention of these apoptotic waves of brain damage is a realistic goal in view of the long delay between the impact event and onset of apoptotic degeneration...

..These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process...

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..These findings are consistent with other recent evidence demonstrating that brief exposure to ethanol, ketamine, or midazolam triggers neuroapoptosis in the developing mouse brain...

..p.) and found that doses >or=50 mg/kg induce a significant neuroapoptosis response. We conclude that propofol induces neuroapoptosis at 1/4 the dose required for surgical anesthesia...

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..Thus, AC1 and AC8 are critical modulators of neurodegeneration induced by activity blockade in the neonatal brain and represent genetic loci that may potentially modify the severity of fetal alcohol syndrome...

..We hypothesize that neuroapoptotic damage in homologous regions of human brain underlies cognitive deficits in FAS and the human brain of FAS victims has a similar capacity to effect functional recovery...

..Rather, conversion of glutamate to glutamine in a reaction involving ammonia helps reverse Müller cell swelling following exposure to exogenous glutamate...

..We conclude that TBOA-sensitive glutamate transporters play an important role in regulating the neurodegenerative effects of glutamate in the rat retina...

..Our findings present one possible mechanism to explain cognitive impairment and reduced brain mass associated with prenatal or postnatal exposure of humans to antiepileptic therapy...

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..CONCLUSIONS: During synaptogenesis, a single ethanol intoxication episode triggers apoptotic cell death of neurons at all levels of the visual system from retina to the visual cortex...

..These results suggest that simulated ischemia enhances glutamate-mediated neurotoxicity in part by depressing glutamate uptake. When glutamate transport is impaired, sub-millimolar glutamate concentrations become profoundly neurotoxic...

..g. phencyclidine, ketamine, benzodiazepines, barbiturates) also suppress neuronal activity and drive developing neurons to commit suicide...

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..These recent findings help clarify important aspects of the fetal alcohol syndrome, and demonstrate the usefulness of an in vivo infant rodent model for studying the neurotoxic effects of ethanol on the developing central nervous system...

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..CONCLUSIONS: This multiple-impact model, delivered within a specifiable force range, results in transient, reversible loss of consciousness, a contra-coup brain injury, and cognitive impairment...

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..These studies will be conducted studies using Muller cell cultures to test this hypothesis. ..

..The long term goals are to clarify the underlying mechanisms and develop improved methods of treating human pediatric acute brain injury conditions. ..

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..In rat hippocampal slices we will study the ability of PCP/sigma opiate compounds to block long term potentiation...