N R Sims

..Further characterization of these mitochondrial responses should help to elucidate the mechanisms of cell death due to cerebral ischemia and possibly point to novel sites for therapeutic interventions in stroke...

..Whether this is a contributor to neurodegeneration or a consequence of it remains unresolved...

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..Each of the procedures produces mitochondria that are well coupled and exhibit high rates of respiratory activity. The procedures require an initial setup time of 45-75 min and between 1 and 3 h for the mitochondrial isolation...

..Thus, this antioxidant pool provides a potentially useful target for therapeutic intervention...

..However, no significant change was seen in activity of either the pyruvate dehydrogenase complex or NADH-ubiquinone oxidoreductase (complex I) when measured directly following treatment of the mitochondria with hydrogen peroxide...

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..The effects of Ca(2+), but not H(2)O(2), were inhibited by cyclosporin A, again implicating the permeability transition in some of the mitochondrial changes...

..However, considerable care is needed in designing and interpreting such studies because of long-lasting changes induced in key properties of these cells by the nucleofection process...

..These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to temporary focal ischemia...

..It also demonstrates the ability to gain a sensitive measure of these mitochondrial changes using flow cytometry...

..They demonstrate the critical importance of this metabolite pool in protecting against peroxynitrite-induced damage in astrocytes and indicate a key contribution in determining the activities of respiratory chain components...

..These findings provide the first evidence of marked sensitivity of NG2-immunoreactivity to severe ischemia and suggest a greater initial resistance of astrocytes compared with neurons and NG2-positive glia to ischemia-reperfusion damage...

..These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive seizures and that the process possibly depends on effects mediated by gap junctions...

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..These findings indicate that inhibition of oxidative metabolism is probably not the primary site of the deleterious effects of nitric oxide and derivatives during early post-ischemic reperfusion...

..These findings are consistent with a role for the glutathione depletion in determining the susceptibility of brain tissue to focal ischemia...

..As such, inhibition of neurogenic inflammation may represent a novel therapeutic target for the treatment of edema following reversible, ischemic stroke...

..The findings directly indicate a role for Connexin 43 in the astrocytic response to injury and suggest that modification of Connexin 43 expression might provide a therapeutic target to alter potentially deleterious astrocytic responses...

..These results indicate that many astrocytes, particularly in the cortex, remain viable and capable of at least some complex oxidative metabolism during the first few hours of recirculation...

..At earlier times, the restricted permeability of the inner mitochondrial membrane was apparently preserved, at least sufficiently to prevent significant diffusion of metabolites between the cytoplasm and the matrix...

..Infarct size was reduced from 46% of the total ischaemic hemisphere in saline-treated animals to 16% following ester treatment. Thus, glutathione monoethyl ester provides neuroprotection following transient focal cerebral ischaemia...

..We therefore conclude that 50 mg kg(-1) EGCG is not a viable intervention for the acute treatment of cerebral ischemia, as it is likely to increase the risk of intracerebral hemorrhaging...