'Reactive change' of the substantia nigra neurons subsequent to striatal infarction in rats

The substantia nigra pars reticulata (SNr) receives the inhibitory gamma-aminobutyric acid (GABA)ergic input from the striatum and globus pallidus, deafferentation of which is supposed to lead to anterograde transneuronal degeneration of the neurons in the nucleus. In the present study, we studied the pathological changes in the deafferented neurons in the rat SNr following massive striatopallidal ischemic lesion produced by transient middle cerebral artery (MCA) occlusion. At 3 days post-ischemia, in association with a decrease of GABAergic afferent fibers, over one-fourth of the neuronal population in the ipsilateral SNr consisted of swollen chromatolytic cells, while no apparent changes were found at day 2. Electron microscopy revealed characteristic ultrastructural findings, including the breakdown of the Golgi apparatus, an accumulation of swollen mitochondria, and disruption of the polysomal clusters of ribosomes. The pathology of these chromatolytic neurons clearly coincides with that of so-called 'reactive change (RC)'. Shrunken dark neurons were widely distributed at 7 days after surgery, and a significant reduction in the number of neurons was found in the SNr at 15 days (P < 0.01). The present study suggested that chromatolytic feature of the SNr neurons may be a consequence of cellular hyper-excitation after the removal of GABAergic inputs, which may lead these neurons finally to cell death.