缺氧/缺血可扩大围产期脑室下区祖细胞的再生能力。
Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone.
作者信息
Yang Z, Levison S W
机构信息
Department of Neurology and Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07101, USA.
出版信息
Neuroscience. 2006 May 12;139(2):555-64. doi: 10.1016/j.neuroscience.2005.12.059. Epub 2006 Feb 24.
Neurons and oligodendrocyte progenitors are highly sensitive to perinatal hypoxic-ischemic injury. As accumulating evidence suggests that many insults to the human infant occur in utero, and preventing brain damage to infants in utero will prove difficult, there is strong rationale to pursue regenerative strategies to reduce the morbidity associated with developmental brain injuries. The purpose of this study was to determine whether a hypoxic-ischemic insult stimulates the neural stem/progenitor cells in the subventricular zone to generate new neurons and oligodendrocytes. Hypoxia-ischemia was induced using the Vannucci rat model on postnatal day-6 pups. Injections of 5'-bromo-2'-deoxyuridine to label cells undergoing DNA synthesis after hypoxia-ischemia revealed that there is a robust proliferative response within the subventricular zone of the injured hemisphere that continues for at least 1 week after the hypoxic-ischemic episode. Using the neurosphere assay to quantify the number of neural stem/progenitor cells in the subventricular zone, we find that there are twice as many neural stem/progenitor cells in the affected dorsolateral subventricular zone at 1 week of recovery and that these cells generate larger spheres in response to growth factors compared with controls. Precursors from the injured hemisphere generate three times as many neurons in vitro and more than twice as many oligodendroglia compared with controls. Hypoxia-ischemia also increases neurogenesis in vivo. Doublecortin positive cells with migratory profiles were observed streaming from the ipsilateral subventricular zone to the striatum and neocortex, whereas, few doublecortin positive cells were found in the contralateral hemisphere after hypoxia-ischemia. These observations provide evidence that the somatic neural progenitors of the subventricular zone participate in the production of new brain cells lost after hypoxia-ischemia.
神经元和少突胶质细胞前体细胞对围产期缺氧缺血性损伤高度敏感。越来越多的证据表明,许多对人类婴儿的损伤发生在子宫内,而要在子宫内预防婴儿脑损伤将被证明是困难的,因此有充分的理由寻求再生策略以降低与发育性脑损伤相关的发病率。本研究的目的是确定缺氧缺血性损伤是否会刺激脑室下区的神经干细胞/前体细胞产生新的神经元和少突胶质细胞。使用Vannucci大鼠模型在出生后第6天的幼崽中诱导缺氧缺血。在缺氧缺血后注射5'-溴-2'-脱氧尿苷以标记正在进行DNA合成的细胞,结果显示损伤半球的脑室下区内有强烈的增殖反应,该反应在缺氧缺血事件后至少持续1周。使用神经球测定法来量化脑室下区神经干细胞/前体细胞的数量,我们发现恢复1周时,受影响的背外侧脑室下区的神经干细胞/前体细胞数量是对照组的两倍,并且与对照组相比,这些细胞对生长因子产生更大的神经球。与对照组相比,来自损伤半球的前体细胞在体外产生的神经元数量是对照组的三倍,少突胶质细胞数量是对照组的两倍多。缺氧缺血还会增加体内神经发生。观察到双皮质素阳性细胞呈迁移状从同侧脑室下区流向纹状体和新皮层,而在缺氧缺血后对侧半球中几乎没有发现双皮质素阳性细胞。这些观察结果提供了证据,表明脑室下区的体神经前体细胞参与了缺氧缺血后丢失的新脑细胞的产生。