Intraventricular administration of GABAA receptor agonist muscimol attenuates the exo‐focal change of the substantia nigra neurons following transient middle cerebral artery occlusion in rats

Abstract

A therapeutic effect of the selective GABAA receptor agonist muscimol on the ‘exo‐focal postischemic death’ was examined in the substantia nigra pars reticulata (SNr) of rats. Continuous intraventricular infusion of muscimol (muscimol‐infusion group) or saline (control group) was initiated from 24 h after the transient middle cerebral artery occlusion for 2 h. At 3 days postischemia, in accordance to a marked depletion of GABAergic afferent fibers in the ipsilateral substantia nigra, strong immunolabelling for 72 kDa heat shock protein (HSP72) appeared in the SNr neurons of the control rats. In contrast, there was no apparent HSP72 immunoreactivity in the ipsilateral SNr in the muscimol infusion group at this stage. In addition, cell density analysis showed that neuronal cell loss in the ipsilateral SNr was effectively prevented by muscinol infusion, as compared to that in the control group, at 15 days after ischemic insult. Thus, the GABA agonist could relieve the deafferented SNr neurons from the lethal metabolic changes responsible for induction of the stress response, which may occur in the course of exo‐focal postischemic death.