Parent Jack M, Vexler Zinaida S, Gong Chao, Derugin Nikita, Ferriero Donna M
Department of Neurology, University of Michigan Medical Center, 4412 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0585, USA.
Ann Neurol. 2002 Dec;52(6):802-13. doi: 10.1002/ana.10393.
The persistence of neurogenesis in the forebrain subventricular zone (SVZ) of adult mammals suggests that the mature brain maintains the potential for neuronal replacement after injury. We examined whether focal ischemic injury in adult rat would increase SVZ neurogenesis and direct migration and neuronal differentiation of endogenous precursors in damaged regions. Focal stroke was induced in adult rats by 90-minute right middle cerebral artery occlusion (tMCAO). Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU) labeling and immunostaining for cell type-specific markers. Brains examined 10-21 days after stroke showed markedly increased SVZ neurogenesis and chains of neuroblasts extending from the SVZ to the peri-infarct striatum. Many BrdU-labeled cells persisted in the striatum and cortex adjacent to infarcts, but at 35 days after tMCAO only BrdU-labeled cells in the neostriatum expressed neuronal markers. Newly generated cells in the injured neostriatum expressed markers of medium spiny neurons, which characterize most neostriatal neurons lost after tMCAO. These findings indicate that focal ischemic injury increases SVZ neurogenesis and directs neuroblast migration to sites of damage. Moreover, neuroblasts in the injured neostriatum appear to differentiate into a region-appropriate phenotype, which suggests that the mature brain is capable of replacing some neurons lost after ischemic injury.
成年哺乳动物前脑脑室下区（SVZ）中神经发生的持续性表明，成熟大脑在损伤后仍保持神经元替代的潜力。我们研究了成年大鼠局灶性缺血损伤是否会增加SVZ神经发生，并引导内源性前体细胞向受损区域直接迁移和神经元分化。通过90分钟的右侧大脑中动脉闭塞（tMCAO）诱导成年大鼠发生局灶性中风。用溴脱氧尿苷（BrdU）标记和针对细胞类型特异性标志物的免疫染色来评估细胞增殖和神经发生。中风后10 - 21天检查的大脑显示，SVZ神经发生显著增加，并且有成链的神经母细胞从SVZ延伸至梗死灶周围的纹状体。许多BrdU标记的细胞在梗死灶附近的纹状体和皮质中持续存在，但在tMCAO后35天，只有新纹状体中BrdU标记的细胞表达神经元标志物。受损新纹状体中新生的细胞表达中等棘状神经元的标志物，这些标志物是tMCAO后大多数丢失的新纹状体神经元的特征。这些发现表明，局灶性缺血损伤会增加SVZ神经发生，并引导神经母细胞迁移至损伤部位。此外，受损新纹状体中的神经母细胞似乎分化为适合该区域的表型，这表明成熟大脑能够替代缺血损伤后丢失的一些神经元。
