Stephen Scheff

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..These results are the first to show a neuroprotective effect of PYC following TBI. They also suggest that the diverse effects of bioflavonoids may provide a unique avenue for possible therapeutic intervention following head trauma...

..To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia...

..The purpose of the current study was to determine the role of the COX isoforms in contributing to pathological processes resulting from TBI by utilizing mice deficient in COX-1 or COX-2...

..These results demonstrate that the inferior temporal gyrus is affected during the prodromal stage of the disease and may underlie some of the early AD-related clinical dysfunctions...

..This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline...

..This article reviews the ultrastructural studies assessing AD-related synaptic loss and the possible compensatory changes in the synaptic complex that occur as a result of the loss in brain connectivity...

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..Animals fed a 1% Cr-diet were afforded greater neuroprotection than animals fed a 0.5% Cr diet. These results support the idea that a Cr-enriched diet can provide substantial neuroprotection in part by suppressing secondary brain injury...

..Comparisons are made between results observed with ultrastructural technique and those utilizing immunohistochemistry to assess changes in synaptic pathology. Possible reasons underlying the synaptic neuropathology are discussed...

..In Alzheimer's disease, one observes a marked reduction in the number of synaptic contacts in important association areas of the cortex and hippocampus. This reduction may be the result of an altered reactive plasticity response...

..Data indicate that cortical synaptic mitochondria appear to have an increased susceptibility to perturbation with age, suggesting that the increased mitochondrial dysfunction observed following injury may impede recovery in aged animals...

..These findings provide support that PYC may provide a promising approach for the treatment of oxidative stress-related neurodegenerative diseases such as AD...

..Glutathione reductase activity also showed an age-dependent decrease. Overall, our data show increased levels of oxidative damage, diminished antioxidant capacities, and increased tissue loss in TBI in aging...

..Early onset of oxidative stress suggests that the initial therapeutic window following TBI appears to be relatively short, and it may be necessary to stagger selective types of antioxidant therapy to target specific oxidative components...

..However, when null mutant mice develop in the absence of central alpha7 expression, it is possible that compensatory changes occur that confound the results obtained...

..These results suggest that a new regionally localized excitatory network forms between dentate granule cells near the injury site within weeks after cortical contusion head injury...

..Failure to modify two major sequelae associated with TBI brings into question the clinical usefulness of PROG as an effective treatment for all types of brain injury...

..Oxidative stress was more localized to the synapses, with levels increasing in a disease-dependent fashion. These correlations implicate an involvement of oxidative stress in Alzheimer disease-related synaptic loss...

..These results suggest that agonists of neuronal nicotinic receptors can be attractive candidates for SCI therapy...

..The relationship between the efficacy of creatine and the magnitude of the insults is discussed...

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..The initial therapeutic window following TBI appears relatively short since oxidative damage occurs as early as 3 h...

..This novel rodent model of SCI provides a significant improvement over existing devices for SCI by reducing variability with a constant preset force to define the injury...

..These preliminary, correlative, and descriptive studies may help develop new hypotheses about CNDM2. We conclude that more work should be performed on human material in the context of CNDM2...

..Levels of oxidative damage that accumulates in the cortex with age does not appear to significantly impair cortical mitochondrial respiration of F344 rats...

..Our results are not consistent with the idea that the precuneus is involved in a special way with plaques or tangles relative to other areas of neocortex...

..Specifically, it defines appropriate statistical analysis of these data in order to facilitate interpretation of results between laboratories and to provide a common methodology for the correct interpretation of SCI behavioral data...

..Although plasticity mechanisms appear to remain intact, synaptic strength deficits in CA1 could limit information throughput in the hippocampus, leading to persistent memory dysfunction...

..Equally important, our results caution the use of lesion volume dimensions or percent tissue sparing at the epicenter as indicators of therapeutic efficacy because neither reflects the actual amount of tissue sparing...

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..In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging...

..Evidence outlined in this review suggests that a variety of CNS pathologies alter dynorphin biogenesis. Such alterations are likely maladaptive and contribute to secondary injury and the pathogenesis of disease...

..This study does not support progesterone as a potential therapeutic agent in spinal cord injury...

..These findings raise the possibility that mitochondrial uncoupling could be a potential novel treatment for acute CNS injuries...

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..These results suggest that E(2) does not provide a viable therapy following SCI...

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..This study stresses the importance of early therapeutic intervention and suggests a window of approximately 1-3 h before greater dysfunction occurs...

..Our data suggest that several pro-apoptotic events occur following TBI, however the translocation of cytochrome c itself and/or other events upstream of caspase activation/inhibition may be sufficient to induce neuronal cell death...

..Identifying experimental injury models that exhibit similar pathology to injury-induced epilepsy in humans should help to elucidate the mechanisms by which the injured brain becomes epileptic...

..The results of this study suggest that alpha7 nAChR agonists may be useful drugs to enhance recovery following brain injury...

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..We also explain some of the evolving methodologies and the academic contributions that have been made due to this motivated group of older Kentuckians...

..Persistent deficits in alpha7* nAChr expression following TBI may contribute to impaired functional outcome following brain injury...

..The 10mg/kg supplementation demonstrated benefit; the 100mg/kg dosage was limited by toxicity. This is the first work to assess a melatonin analog in SCI...

..Regulation of MR and GR expression following TBI may influence hippocampal neuron viability by modulating glucocorticoid signaling after injury...

..In both injury groups and in all hippocampal regions, more FJB-positive neurons were seen at the earlier times post injury (1 and 2 days) than at 7 days. FJB appears to be a reliable marker for neuronal vulnerability following TBI...

..In addition, they also should be avoided in experiments testing effects on hepatic tissue...

..Serum data suggests that C-tau levels are dependent both on a compromised blood-brain barrier as well as release of TBI biomarkers from the brain, which has implications for the study of human serum TBI biomarkers...

..Successful completion of the proposed studies will lead to new insights into the mechanisms underlying MCI and early AD and contribute to the development of effective pharmacologic therapies for AD. ..

..Specific aim #4 will use a 'creatine-supplemented' dietary intervention that enhances cytosolic phosphocreatine and increases the ability of neurons to produce ATP, an intervention to reverse the age-related response to TBI. ..

..These studies will significantly enhance our understanding of the mechanisms following TBI and hopefully lead to therapies resulting in increased recovery. ..

..Successful completion of the proposed studies will lead to new insights into the mechanisms underlying MCI and early AD and contribute to the development of effective pharmacologic therapies for AD. ..