Immunohistochemical observations on GABA and glutamate decarboxylase (GAD) in rats subjected to cardiac arrest cerebral ischemia (CACI) revealed strikingly early changes in the immunoreactivity of GABAergic neuronal elements expressed in the widespread swelling and increased GABA and GAD immunostaining of GABAergic terminals and boutons. These changes appeared to be generally reversible with the exception of the nucleus reticularis thalami (NRT) which showed 80% neuronal loss. GABAergic terminals in the adjacent ventral thalamic nuclei (VTN) showed, approximately 7 days after their initial disintegration, a sprouting of new terminals, which reached its peak 1 month after ischemia. This coincided with the cessation of audiogenic seizures and the return to the normal paired-pulse stimulation patterns in the hippocampus, indicating a return of GABAA inhibitory function. The hybridization assays with GAP-43 revealed strong mRNA expression limited to the NRT of rats sacrificed 7 days after CACI. The described correlations between morphologic evidence of sprouting of GABAergic terminals, and clinical cessation of susceptibility to audiogenic seizures, as well as electrophysiologic demonstration of the return of GABAA inhibitory function in the hippocampus indicate the regenerative effort of the brain tissue subjected to ischemia and provide criteria for evaluating various therapeutic measures in future studies.
