Expression of GAD (M(r) 67,000) and its messenger RNA in basal ganglia and cerebral cortex after ischemic cortical lesions in rats.

Glutamic acid decarboxylase (GAD) is present in most efferent neurons of the striatum and in interneurons both in the striatum and the cerebral cortex. We have examined the effects of unilateral lesions of the frontoparietal cortex by thermocoagulation of pial vessels in adult rats on GAD expression in the basal ganglia and in the contralateral cerebral cortex. Levels of GAD were measured in the striatum and its target areas (pallidum and substantia nigra) with radioimmunohistochemistry and an antibody specific for GAD (M(r) 67,000: GAD67); levels of the corresponding mRNA were measured at the single-cell level by in situ hybridization histochemistry with a [35S]RNA probe. Five days after surgery, GAD67 immunoreactivity was markedly increased in striatal target areas on the side of the lesion. In the striatum, increases in immunoreactivity were small at 5 days, larger at 3 weeks, and accompanied by an increase in mRNA levels lasting up to 3 months after surgery. In contrast, in the frontal cortex contralateral to the lesion, levels of labeling for GAD67 mRNA per neuron were decreased 3 weeks and 3 months after surgery. The results suggest that local ischemic lesions of cerebral cortex in adult rats lead to prolonged and opposite alterations in GAD67 synthesis in basal ganglia and contralateral cortex.