Masuda Tadashi, Isobe Yoshiaki, Aihara Noritaka, Furuyama Fujiya, Misumi Sachiyo, Kim Tae-Sun, Nishino Hitoo, Hida Hideki
Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Neurosci Lett. 2007 Sep 25;425(2):114-9. doi: 10.1016/j.neulet.2007.08.039. Epub 2007 Aug 25.
Neural stem/progenitor cells (NPCs) reside in the subventricular zone (SVZ) and dentate gyrus in the adult mammalian brain. It has been reported that endogenous NPCs are activated after brain insults such as ischemic stroke. We investigated whether proliferation and migration of endogenous NPCs are increased after a collagenase-induced small intracerebral hemorrhage (ICH) near the internal capsule in rats. Bromodeoxyuridin (BrdU) administration for 14 days after ICH (post-labeling) resulted in an increase in the number of BrdU-positive cells as shown in both ipsilateral and contralateral SVZs. BrdU treatment given for 2 days before ICH to label endogenous NPCs (pre-labeling), caused more BrdU-positive cells to be detected in the ipsilateral dorsal striatum (dSTR) compared to those in the contralateral dSTR 14 days after ICH. BrdU- and doublecortin (Dcx)-positive cells were found in the ipsilateral STR. An increase in the number of Dcx-positive migrating immature neurons was found in the dSTR and peri-hemorrhage area 14 days after ICH, and a cluster of Dcx-positive cells was found in the STR around the lesion 28 days after ICH. Matrix metalloproteinase-2 (MMP-2) was strongly expressed in wide area of the injured brain, particularly around the lesion 14 and 28 days after ICH. Dcx- and MMP-2-positive cells were detected in the ipsilateral STR near the lesion. These data suggest that collagenase-induced ICH enhances the proliferation of endogenous NPCs and the migration of newly born neuroblasts toward the hemorrhage area.
神经干细胞/祖细胞（NPCs）存在于成年哺乳动物大脑的脑室下区（SVZ）和齿状回中。据报道，内源性NPCs在诸如缺血性中风等脑损伤后会被激活。我们研究了大鼠内囊附近胶原酶诱导的小脑出血（ICH）后，内源性NPCs的增殖和迁移是否增加。ICH后给予溴脱氧尿苷（BrdU）14天（标记后），结果显示同侧和对侧SVZ中BrdU阳性细胞数量增加。ICH前2天给予BrdU处理以标记内源性NPCs（标记前），与ICH后14天对侧背侧纹状体（dSTR）相比，同侧dSTR中检测到更多BrdU阳性细胞。在同侧纹状体中发现了BrdU和双皮质素（Dcx）阳性细胞。ICH后14天，在dSTR和出血周边区域发现Dcx阳性迁移未成熟神经元数量增加，ICH后28天，在损伤周围的纹状体中发现一群Dcx阳性细胞。基质金属蛋白酶-2（MMP-2）在损伤大脑的广泛区域强烈表达，尤其是ICH后14天和28天在损伤周围。在损伤附近的同侧纹状体中检测到Dcx和MMP-2阳性细胞。这些数据表明，胶原酶诱导的ICH增强了内源性NPCs的增殖以及新生神经母细胞向出血区域的迁移。
