Astroglial response in the excitotoxically lesioned neostriatum and its projection areas in the rat

The anatomical distribution of the astrocytic glial reactions, following ibotenic acid-induced neuronal degeneration of the neostriatum in the rat, has been studied immunohistochemically using an antibody directed against the astrocytic marker, glial fibrillary acidic protein. The acute astroglial response to the excitotoxic lesion, determined 7 days post lesion, was compared with a sham-operated group and a chronic group that had received the excitotoxic lesion 6 months prior to histological evaluation. Total doses of 16-20 micrograms ibotenic acid injected unilaterally into the head of the neostriatum caused not only a marked neuronal cell loss but was also accompanied by a large increase in the number and size (about 5 times) of glial fibrillary acidic protein-stained astrocytes throughout the neostriatum by 7 days after lesion. Reactive astrocytes were also observed in the major neostriatal projection areas, the globus pallidus and the substantia nigra pars reticulata, at 7 days post lesion, although no neuronal cell loss could be detected in these regions using regular Cresyl Violet staining. Previous studies of lesions identical to the ones used here have shown that globus pallidus and substantia nigra are deafferented as a result of the neostriatal neuronal degeneration. The reactive astrocytes in the striatal projection areas had a 3-5 times larger size than control astrocytes from the same anatomical region. In animals that received a larger dose of ibotenic acid into the neostriatum (25 micrograms), neuronal cell loss was also observed in the neocortex and reactive glial fibrillary acidic-stained astrocytes were found in the entire neocortex of the injected hemisphere. In the chronic group, 6 months after the excitotoxic lesion, the astroglial response was clearly diminished or absent in the major neostriatal projection areas, but was still present within the lesioned neostriatum. The results suggest that focal neuronal destruction can result in widespread astrocytic glial reactions which follow the anatomical connectivity of the lesioned area. This may have implications for the understanding of the multifocal distribution of glial reactions seen in patients with striatal degeneration as a result of Huntington's disease.