Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

Abstract

In recent years, studies on cell regeneration in the adult mammalian central nervous system have brought about the possibility of new strategies for treating neurological disorders. Many researchers have examined molecular/cellular-based approaches in vitro, while little has been determined about the modulatory processes affecting cellular proliferation and differentiation in vivo. We report here a new strategy to investigate cellular proliferation, differentiation, and regeneration using an experimental animal model for functional activation of the cerebral cortex in rats. The unilateral cerebral cortex was extensively activated by induction of cortical spreading depression (SD), characterized as propagation of neuronal/glial membrane depolarization. Cellular proliferation in the animals was assessed using histochemical studies with BrdU, an analog of thymidine. SD resulted in a dramatic increase in BrdU-labeled cells in the cortical hemisphere that had undergone the SD, depending on the number of elicited SD events. Immunohistochemical studies revealed that 53% of the BrdU-labeled cells in the SD-generated cortex were immunopositive for NG2, a maker of oligodendrocyte progenitor cells, while 25% were immunopositive for OX-42, a maker of microglia, at 3 days after SD. These studies indicate that neural activation induces cellular proliferation in the cerebral cortex, and that the cells subsequently differentiate into glial progenitors or microglia within 3 days.