Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated c...

Spironolactone has produced beneficial effects in animal models of neurodegenerative disorders. However, the underlying mechanisms of this agent on neurons and glia are mostly unknown. Therefore, we aimed to show the effects of spironolactone and fludrocortisone, a mineralocorticosteroid receptor agonist, on neuronal and glial toxicity induced by N-methyl-D-aspartate (NMDA) activation and chlor...

Extensive programmed cell death (PCD) occurs in the developing nervous system. Neuronal death occurs, at least in part, because neurons are produced in excess during development and compete with each other for the limited amounts of the survival-promoting trophic factors secreted by target tissues. Neuronal death is apoptotic and utilizes components that are conserved in other PCD pathways. In ...

Hypoxia/ischaemia is known to trigger neuronal death, but the role of neuronal nitric oxide synthase (nNOS) in this process is controversial. Nitric oxide (NO) inhibits cytochrome oxidase in competition with oxygen. We tested whether NO derived from nNOS synergises with hypoxia to induce neuronal death by inhibiting mitochondrial cytochrome oxidase. Sixteen hours of hypoxia (2% oxygen) plus deo...

N-methyl-D-aspartate receptors (NMDARs) play an important role in cell survival versus cell death decisions during neuronal development, ischemia, trauma, and epilepsy. Coupling of neurons by electrical synapses (gap junctions) is high or increases in neuronal networks during all these conditions. In the developing CNS, neuronal gap junctions are critical for two different types of NMDAR-depend...

Extensive neuronal cell death during development is believed to be due to a limiting supply of neurotrophic factors. In vitro studies suggest that axon guidance molecules directly regulate neuronal survival, raising the possibility that they play a direct role in neuronal cell death in vivo. However, guidance errors may also influence survival indirectly due to loss of target-derived neurotroph...

Hypoglycemia-induced brain injury is a common and serious complication of intensive insulin therapy experienced by Type 1 diabetic patients. We previously reported that hypoglycemic neuronal death is triggered by glucose reperfusion after hypoglycemia rather than as a simple result of glucose deprivation. However, the precise mechanism of neuronal death initiated by glucose reperfusion is still...