Cultured rat embryonic cortical neurons undergo apoptosis when treated with the topoisomerase-I inhibitor camptothecin. Pharmacological or molecular caspase inhibition prevents apoptosis, but the neurons still die in a delayed nonapoptotic manner. Here we examine the mechanisms leading to such caspase-independent death, focusing on events related to mitochondrial malfunction, which accompanies ...

Hypoxia-induced delayed neuronal death is known to require de novo gene expression; however, the molecular mediators that are involved remain undefined. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), in addition to promoting the expression of adaptive genes under conditions of hypoxia, has been implicated as being a necessary component in p53-mediated cell death in tumor...

Considerable evidence suggests that Ca(2+)-permeable AMPA receptors are critical mediators of the delayed, selective neuronal death associated with transient global ischemia and sustained seizures. Global ischemia suppresses mRNA and protein expression of the glutamate receptor subunit GluR2 and increases AMPA receptor-mediated Ca(2+) influx into vulnerable neurons of the hippocampal CA1 before...

After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in various conditions including ischemia. We demonstrate that loss of endogenous cyclin-dependent kinase (Cdk) inhibitor p16(INK4a) is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral isch...

We investigated progression and recovery of neuronal damage during and after global cerebral ischemia in gerbils after bilateral occlusion of the common carotid arteries, using the immunohistochemical method (reaction for tubulin and creatine kinase BB-isoenzyme). The earliest, but reversible, ischemic lesions occurred after 3 minutes' ischemia in the subiculum-CA1 and CA2 regions of the hippoc...

Article history:Received 24 June 2008Revised 2 December 2008Accepted 3 December 2008Available online 24 December 2008Hypoxic–ischemic injury (HI) to the neonatal brain results in delayed neuronal death with accompanyinginflammation for days after the initial insult. The aim of this study was to depict delayed neuronal death afterHI using Manganese-enhanced MRI (MEMRI...

The mechanisms by which neurons die after cerebral ischemia and related conditions in vivo are unclear, but they are thought to involve voltage-dependent Na+ channels, glutamate receptors, and nitric oxide (NO) formation because selective inhibition of each provides neuroprotection. It is not known precisely what their roles are, nor whether they interact within a single cascade or in parallel ...

BACKGROUND AND PURPOSE We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). METHODS Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). RESULTS OGD persistently increased ...