IMMUNOHISTOCHEMICAL EVIDENCE FOR DYSREGULATION OF THE GABAERGIC SYSTEM IPSILATERAL TO PHOTOCHEMICALLY INDUCED CORTICAL INFARCTS IN RATS

Deficits of GABAergic transmission have been reported to occur in tiss ue surrounding ischemic cortical lesions between a few days and severa l weeks after the insult. In the present experiments, we used immunohi stochemistry with antibodies against parvalbumin and two major subunit s of the GABA(A) receptor (alpha 1, alpha 2) to characterize the event s that underlie these changes at different levels of circuit organizat ion. Neocortical infarcts (similar to 2 mm diameter) consistently affe cting medial parts of the primary somatosensory cortex were induced ph otochemically in adult male Wistar rats; animals were allowed to recov er for one week before perfusion-fixation. When compared to controls t he pattern of immunoreactivity had changed for the alpha 1 subunit of the GABA(A) receptor seven days after the insult. Ipsilateral to the i schemic lesions, we found a decrease in staining intensity reaching up to 4 mm laterally, resulting in a partial or complete absence of the normal laminar staining pattern. No consistent changes were observed f or the alpha 2 subunit. Parvalbumin staining revealed pathological alt erations in a rim of tissue surrounding the infarct, measuring up to 1 mm from the border of the infarcts. Parvalbumin-positive interneurons in this region showed signs of degeneration; both a reduction of the number of dendrites and, to a lesser extent and only immediately adjac ent to the ischemic lesions, a reduction of the number of parvalbumin- positive neurons was readily apparent. The results provide evidence fo r both a differential regulation of two GABA(A) receptor subunits and degenerative changes of parvalbumin-containing interneurons ipsilatera l to cortical infarcts. The relevance of these findings for mechanisms underlying long-term recovery, transient functional deficits and post infarct seizures warrants further investigation. (C) 1998 IBRO. Publis hed by Elsevier Science Ltd.