Endogenous Neural Stem Cell Proliferation after Intracerebral Hemorrhage in Rat Model

ABSTRACT

BACKGROUND: Focal and global ischemia was shown to be potent in inducing neurogenesis in the subventricular zone (SVZ). However, it is unknown whether these new neurons can replace those lost following damage, such as intracerebral hemorrhage (ICH). We tested the hypothesis that ICH leads to an increase of cell proliferation in the SVZ and that the new neurons migrate into the damaged area of the hemorrhagic striatum. METHODS: Experimental ICH was induced by an intrastriatal administration of collagenase in adult rats. Proliferating cells were labeled with intraperitoneal injections of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) over 3-day periods before sacrificing the animals, 0, 6, 9, 12 or 15 days after ICH. BrdU+ cells in the dorsolateral SVZ and the striatum were counted in three coronal sections per animal. RESULTS: BrdU+ cells were found in the bilateral SVZs, the third ventricle, and ipsilateral cortex near the needle insertion site. The number of BrdU+ cells in the damaged striatum and the ipsilateral SVZ reached maximum counts 9 days after ICH. The BrdU+ cells were double-labeled with a neuronal marker, neuronal nuclear antigen (NeuN), and a glial marker, the glial fibrillary acidic protein (GFAP), in the hemorrhagic hemisphere. The percentage of BrdU+ cells that expressed NeuN and GFAP was about 13% and about 72%, respectively. CONCLUSIONS: These results suggest new evidence that endogenous neural stem cells are activated in the dorsolateral SVZ after ICH, and that the newly formed cells play a role for ICH-induced neurogenesis in what may be an adaptive process that contributes to recovery after a hemorrhagic stroke.