Hayashi Takeshi, Iwai Masanori, Ikeda Tomoaki, Jin Guang, Deguchi Kentaro, Nagotani Shoko, Zhang Hanzhe, Sehara Yoshihide, Nagano Isao, Shoji Mikio, Ikenoue Tsuyomu, Abe Koji
Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Brain Res. 2005 Mar 15;1038(1):41-9. doi: 10.1016/j.brainres.2004.12.048.
Ischemia/hypoxia (I/H) causes severe perinatal brain disorders such as cerebral palsy. The neonatal brain possesses much plasticity, and to enhance new cell production would be an innovative means of therapy for such disorders. In order to elucidate the dynamic changes of neural progenitor cells in the neonatal brain after ischemia, we investigated new cells production in the subventricular zone and subsequent migration of these cells to the injured area. Newly produced cells were confirmed by incorporation of bromodeoxyuridine (BrdU), and attempt for differentiation was investigated by immunohistochemistry for molecular markers of each cellular lineage. In the sham-control brain, there were many BrdU-labeled cells which gradually decreased as the animal becomes older. Many of these cells were oligodendroglial progenitor or microglial cells. Although there were only few neuronal cells labeled for BrdU in the sham-control, they dramatically increased after I/H. They were located at just beneath the subventricular zone where the progenitor cells reside and to the injured area, indicating that newly produced cells migrated to the infarct region and differentiated into neuronal precursor cells in order to compensate the lost neural cells. We found that BrdU-labeled astroglial, oligodendroglial progenitor, and microglial cells were also increased after I/H, suggesting that they also play active roles in recovery. Progenitor cells may have potential for treating perinatal brain disorders.
缺血/缺氧（I/H）会导致严重的围产期脑部疾病，如脑瘫。新生大脑具有很大的可塑性，增强新细胞的产生将是治疗此类疾病的一种创新方法。为了阐明新生儿大脑缺血后神经祖细胞的动态变化，我们研究了脑室下区新细胞的产生以及这些细胞随后向损伤区域的迁移。通过掺入溴脱氧尿苷（BrdU）来确认新产生的细胞，并通过免疫组织化学检测每种细胞谱系的分子标记来研究分化尝试。在假手术对照大脑中，有许多BrdU标记的细胞，随着动物年龄的增长，这些细胞逐渐减少。其中许多细胞是少突胶质前体细胞或小胶质细胞。虽然在假手术对照中只有少数神经元细胞被BrdU标记，但在I/H后它们显著增加。它们位于祖细胞所在的脑室下区正下方以及损伤区域，这表明新产生的细胞迁移到梗死区域并分化为神经元前体细胞，以补偿丢失的神经细胞。我们发现，I/H后BrdU标记的星形胶质细胞、少突胶质前体细胞和小胶质细胞也增加了，这表明它们在恢复过程中也发挥着积极作用。祖细胞可能具有治疗围产期脑部疾病的潜力。
