Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
Neuropathol Appl Neurobiol. 2013 Aug;39(5):510-8. doi: 10.1111/j.1365-2990.2012.01301.x.
Adult neurogenesis is well described in the subventricular zone of the lateral ventricle walls and in the subgranular zone of the hippocampal dentate gyrus. However, recent studies indicate that self-renewal of neural stem cells (NSCs) is not restricted to these niches, but that diverse areas of the adult brain are capable of generating new neurones and responding to various pathological alterations. In particular, NSCs have been identified in circumventricular organs (CVOs) of the adult mouse brain.
In order to detect possible neural stem or progenitor cells in CVOs of the human brain, we analysed post mortem human brain tissue from patients without neuropathological changes (n = 16) and brains from patients with ischaemic stroke (n = 16).
In all analysed CVOs (area postrema, median eminence, pineal gland and neurohypophysis) we observed cells with expression of early NSC markers, such as GFAP, nestin, vimentin, OLIG2 and PSA-NCAM, with some of them coexpressing Ki67 as a marker of cell proliferation. Importantly, stroke patients displayed an up to fivefold increase with respect to the relative number of Ki67- and OLIG2-expressing cells within their CVOs.
Our findings are compatible with a scenario where CVOs may serve as a further source of NSCs in the adult human brain and may contribute to neurogenesis and brain plasticity in the context of brain injury.
成人神经发生在侧脑室壁的室下区和海马齿状回的颗粒下区得到了很好的描述。然而,最近的研究表明,神经干细胞(NSCs)的自我更新不仅局限于这些龛位,而是大脑的不同区域都有能力产生新的神经元,并对各种病理改变做出反应。特别是,在成年老鼠的脑的室周器官(CVOs)中已经鉴定出了 NSCs。
为了在人脑的 CVOs 中检测到可能的神经干细胞或祖细胞,我们分析了没有神经病理学变化的患者(n = 16)和患有缺血性中风的患者(n = 16)的死后人脑组织。
在所有分析的 CVOs(后连合区、正中隆起、松果体和神经垂体)中,我们观察到表达早期 NSC 标志物的细胞,如 GFAP、巢蛋白、波形蛋白、OLIG2 和 PSA-NCAM,其中一些细胞共同表达 Ki67 作为细胞增殖的标志物。重要的是,中风患者的 CVOs 中 Ki67 和 OLIG2 表达细胞的相对数量增加了五倍。
我们的发现与 CVOs 可能作为成人脑内 NSCs 的另一个来源,并可能有助于脑损伤背景下的神经发生和大脑可塑性的情况相一致。