Neuroprotection of cultured foetal rat hippocampal cells against glucose deprivation: are GABAergic neurons less vulnerable or more sensitive to TCP protection?

In the rat brain, hippocampal neurons are particularly sensitive to seconda ry excitotoxic injury induced by ischaemia or hypoglycaemia. To determine s ome distinctive features of vulnerability among neuronal phenotypes in the hippocampus following a metabolic insult, we used an in vitro model of mild glucose deprivation. Primary cultures from the rat hippocampus (21 days in vitro) were deprived of glucose for 4 h and then were returned to the stan dard medium for 24 or 48 h. Survival of the GABAergic neuronal population w as evaluated both by measuring [H-3]GABA uptake and by counting GAD(65)-imm unostained cells. This was compared with the survival of the total neuronal population evaluated by counting the neurofilament-200-immunostained cells . Glucose deprivation for 4 h followed by a recovery period of 48 h induced a decrease of 59% and 40% in the number of GAD(65)- and neurofilament-200- immunostained cells, respectively. Thus, GABAergic neurons were slightly mo re vulnerable to glucose deprivation than the other neurons in the hippocam pal cell cultures. When the excitotoxic component of cellular death was blo cked in the presence of TCP, an NMDA-antagonist, the survival of GABAergic neurons was almost complete after 48 h of recovery. In contrast, measuremen ts of the release of lactate dehydrogenase in the medium indicated that TCP largely protected hippocampal cells after 24 h but was ineffective after 4 8 h. This observation was confirmed by immunostaining data which showed tha t after 48 h TCP did not significantly increase the survival of neurofilame nt-200-immunostained cells. These results indicate that after glucose depri vation and a recovery period of 48 h, GABAergic neurons in hippocampal cell cultures are not more resistant than other neurons but they are more sensi tive to TCP protection.