Experimental brain injury induces activation of neural stem cells in the forebrain subependyma.

The subependymal zone (SEZ) of adult mammalians contains relatively quiescent neural stem cells that can be stimulated toward proliferation in response to specific stimuli. We used immunophenotypization to demarcate sharp boundaries of the SEZ and identify cell populations constituting the rat intact SEZ. Moreover, we studied the proliferation rates of SEZ cells under various experimental conditions that induced the lesion of the neighboring brain parenchyma or SEZ cells. Four groups of experimental animals included rats that were (1). mechanically injured, (2). intracerebrally injected with kainic acid, (3). treated with intracerebral injection of neurotoxic sodium nitroprusside, or (4). treated with intraperitoneal injection of cyclophosphamide. Animals were killed after 4 or 8 days. The number of SEZ proliferating cells was counted in coronal sections immunostained for proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine. Our results show that all types of injury induced activation of SEZ neural stem cells, evidenced by the increase of corresponding proliferation indices when compared with intact brains. The increase was detected not only in ipsilateral but also in contralateral (intact) SEZ. After mechanically induced trauma of the right cerebral hemisphere, the increase in the number of SEZ proliferative cells was observed after 8 days in the right cerebral ventricle. Injection of kainic acid induced early responses in SEZ cells that reached the highest values. Injury induced by sodium nitroprusside evoked early increase of PCNA, whereas bromodeoxyuridine increase was detected in SEZ at day 8. Cyclophosphamide activated SEZ proliferation after 4 days, and the level of proliferation indices remained approximately the same at day 8. Our data suggest that each type of brain injury induces a SEZ proliferative response with a specific temporal pattern.