Regulation of growth inhibitory mechanisms following cortical injury in the adult rat brain

Injury to the adult central nervous system results in cellular and molecular mechanisms that prevent repair of damaged nerve tracts and impede functional recovery. Nogo-A is a myelin protein and major contributor to the inhibitory environment encountered by growing axons in the mature brain. We used two different cortical lesions to (1) determine whether levels of Nogo-A are regulated differently after cortical injuries that do or do not support sprouting of crossed corticostriatal axons, and (2) to examine the effect of injury induced mechanisms on Nogo-A expression after an injury that supports crossed corticostriatal sprouting. Using immunohistochemistry and cell counting using a confocal microscope, we showed that an aspiration (ASP) cortical injury which does not support sprouting induces a 3.2 fold increase of Nogo-A in corpus callosum oligodendrocytes. In contrast, a cortical thermocoagulation (TCL) injury induced by coagulation of pial blood vessels supports sprouting, and does not increase Nogo-A. The lack of increase in Nogo-A after TCL is likely important for sprouting of crossed corticostriatal fibers, because previous work has shown that neutralization of Nogo-A allows for sprouting after ASP. Levels of Nogo-A mRNA were slightly increased in corpus callosum oligodendrocytes; however, the magnitude of this change is not sufficient to account for the robust increase in Nogo-A protein. Increased expression of Nogo-A transcript also occurred in the ipsilateral hemisphere after both ASP and TCL in response to cortical damage. Taken together, regulation of Nogo-A protein in oligodendrocytes and not constitutive expression is inhibitory for sprouting after injury.;Previous work in the laboratory has demonstrated that blockade of slow wave activity induced by TCL with the voltage gated sodium channel antagonist tetrodotoxin (TTX) also inhibits sprouting after TCL. We next examined lesion specific mechanisms that may regulate Nogo-A expression after cortical injury. We used local infusion of TTX and confocal cell counting to examine the hypothesis that blocking synchronized cortical activity will increase Nogo-A expression in corpus callosum oligodendrocytes after TCL. However, we found that local infusion of TTX did not affect Nogo-A expression after TCL. This suggests that synchronous activity is not the mechanism which suppresses Nogo-A increase after TCL.