To examine the role of Ca2+ in early neuronal death, we studied the impact of free intracellular calcium concentration ([Ca2+]i) on survivability in populations of cultured mouse spinal neurons. We asked whether early neurotoxicity was triggered by Ca2+ influx, whether elevated [Ca2+]i was a predictive indicator of impending neuronal death, and whether factors other than [Ca2+]i increases influ...

The interaction between astrocytes and neurons is examined from the standpoint of glutamate neurotoxicity. The review details 1. the distribution of glutamate transporters on astrocytes and neurons, provoking a reformulation of the interdependence between these two cell types in removing extracellular glutamate and preventing excitotoxic injury; 2. the potential involvement of aberrant glutamat...

BACKGROUND The recent literature suggests that free radicals and reactive oxygen species may account for many pathologies, including those of the nervous system. MATERIALS AND METHODS The influence of various reactive oxygen species on the rate of glutamate uptake by astrocytes was investigated on monolayers of primary cultures of mouse cortical astrocytes. RESULTS Hydrogen peroxide and per...

Loss of retinal ganglion cells (RGCs) is a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due to central artery occlusion, anterior ischemic optic neuropathy and may be significant in optic neuritis, optic nerve trauma, and AIDS. Recent research indicates that neurotoxicity is caused by excessive stimulation of receptors for excitatory amino acids (EAAs). In particula...

The protective effect of a L-type calcium channel blocker, nimodipine, on cell injury induced by oxygen-glucose deprivation (OGD) in PC12 cells was investigated. PC12 cells were exposed to in-vitro oxygen-glucose deprivation (30 minutes and 60 minutes respectively) in the presence or absence of nimodipine (10mM/L) in three different time schedules (pre-24h, pre-3h and concurrently). Cellular vi...

Reduction in GluR2 subunit expression and subsequent increases in AMPA receptor mediated Ca(2+) currents were postulated to exacerbate glutamate neurotoxicity following seizures or global ischemia. To directly test the effects of shifting the GluR1/GluR2 subunit ratio on excitotoxicity, GluR2 antisense deoxyoligonucleotides (AS-ODNs) were applied to dissociated hippocampal cultures for 1-8 days...

Heme oxygenase-1 (HO-1) is an inducible, detoxifying enzyme that is critical for limiting oxidative stress, inflammation, and cellular injury within the CNS and other tissues. Here, we demonstrate a deficiency of HO-1 expression in the brains of HIV-infected individuals. This HO-1 deficiency correlated with cognitive dysfunction, HIV replication in the CNS, and neuroimmune activation. In vitro ...