Cerebellar Injury Induces NADPH Diaphorase in Purkinje and Inferior Olivary Neurons in the Rat

Abstract

NADPH diaphorase (NADPH-D) histochemistry was examined following cerebellar lesions induced by stab or knife cuts. A population of Purkinje cells adjacent to the injury became NADPH-D positive after either type of lesion. These cells appeared by 3 days postlesion and were still seen after 6 weeks. Somata of reactive cells shrank gradually and were reduced about 38% in size by 6 weeks after lesion. In the inferior olive of animals subjected to cerebellar knife cut, NADPH-D-positive cells were found in the beta nucleus, dorsal cap, and subnucleus C. These cells became NADPH-D positive 5 days postlesion, were shrunken at 4 weeks postlesion, and were reduced about 26% in somata size by 6 weeks after lesion. Other cerebellar afferents did not exhibit obvious NADPH-D induction following these lesions. In unlesioned animals, no Purkinje cells or inferior olivary neurons were NADPH-D positive. The present study demonstrates that cerebellar damage induces NADPH-D, a marker for nitric oxide (NO) synthase, in Purkinje cells and inferior olivary neurons. In addition, these reactive neurons exhibit long-term degenerative changes. Taken together with previous studies, these findings indicate that NO, produced by the lesion-induced nitric oxide synthase (NOS), may contribute to the degeneration of brain neurons after injury. The lack of NADPH-D-positive neurons in either Purkinje or the inferior olivary neurons in nonlesioned animals indicates that this may provide a useful model system to study injury-induced NOS in brain.