内在性神経幹細胞の移動及び神経細胞産生に及ぼす外傷性脳損傷の影響

抄録

In mammalian brain, young neurons generated from the subventricular zone of the lateral ventricle migrate tangentially along the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they differentiate into mature neurons. In order to evaluate an initiation of neurogenesis induced by traumatic brain injury (TBI) in the rats, the response of neural precursors was investigated. The cortical contusion was induced by the controlled cortical impact device (CCI). The rats were injected bromodeoxyuridine (BrdU) intraperitoneally to label proliferating cells. The newly-generated neurons were visualized by doublecortin (DCX) immunohitsochemistry. Within several hours, the DCX expression appeared to be increased throughout the RMS. In such short periods, the upregulated DCX-expression was not accompanying increase in the number of BrdU-positive proliferating cells, suggesting that post-mitotic neural precursors could re-express developmental characteristics. Following transection of the OB, however, although a contusion existed beside the RMS, the DCX expressing young neurons appeared to remain in the RMS and never move to the injury sites. In addition, in order to examine a period of DCX expression in newly-generated neurons, an anti-proliferating agent, Ara-C was administered continuously into the lateral ventricle, the DCX immunoreactivity was disappeared completely within 14 days, indicating that the DCX could exist in the first 2 weeks from the beginning of neuronal proliferation. The results of the present study indicate that, although the neurogenesis in the SVZ-RMS-OB pathway can be enhanced readily in response to TBI, the most of newly-generated neurons do not contribute to the repair of trauma-induced tissue damages. Further study will be necessary to elucidate precise mechanism which regulates the migration and differentiation of endogenous neural precursors, which may lead to a novel therapy which improves functional outcome of the patients suffered from TBI.