Sgubin D, Aztiria E, Perin A, Longatti P, Leanza G
B.R.A.I.N. Centre for Neuroscience, Department of Physiology and Pathology, University of Trieste, and Neurosurgery Unit, Treviso Hospital, Italy.
J Neurosci Res. 2007 Jun;85(8):1647-55. doi: 10.1002/jnr.21303.
In the adult human brain, the presence of neural stem cells has been documented in the subgranular layer of the dentate gyrus of the hippocampus and in the subventricular zone of the lateral ventricles. Neurogenesis has also been reported in rodent models of ischemic stroke, traumatic brain injury, epileptic seizures, and intracerebral or subarachnoid hemorrhage. However, only sparse information is available about the occurrence of neurogenesis in the human brain under similar pathological conditions. In the present report, we describe neural progenitor cell proliferation in the brain of patients suffering from subarachnoid hemorrhage (SAH) resulting from ruptured aneurysm. Ten cerebral samples from both SAH and control patients obtained, respectively, during aneurysm clipping and deep brain tumor removal were analyzed by reverse transcription followed by polymerase chain reaction (RT-PCR) and/or immunohistochemistry (IHC). In tissue specimens from SAH patients, RT-PCR and IHC revealed the expression of a variety of markers consistent with CNS progenitor cells, including nestin, vimentin, SOX-2, and Musashi1 and -2. In the same specimens, double immunohistochemistry followed by confocal analysis revealed that Musashi2 consistently colocalized with the proliferation marker Ki67. By contrast, no such gene or protein expression profiles were detected in any of the control specimens. Thus, activation of neural progenitor cell proliferation may occur in adult human brain following subarachnoid hemorrhage, possibly contributing to the promotion of spontaneous recovery, in this pathological condition.
在成人大脑中,海马齿状回颗粒下层和侧脑室室管膜下区已被证实存在神经干细胞。在缺血性中风、创伤性脑损伤、癫痫发作以及脑内或蛛网膜下腔出血的啮齿动物模型中也有神经发生的报道。然而,关于在类似病理条件下人类大脑中神经发生的情况,仅有稀少的信息。在本报告中,我们描述了因动脉瘤破裂导致蛛网膜下腔出血(SAH)的患者大脑中神经祖细胞的增殖情况。分别在动脉瘤夹闭术和深部脑肿瘤切除术中获取的10份SAH患者和对照患者的脑样本,通过逆转录聚合酶链反应(RT-PCR)和/或免疫组织化学(IHC)进行分析。在SAH患者的组织标本中,RT-PCR和IHC显示了多种与中枢神经系统祖细胞一致的标志物的表达,包括巢蛋白、波形蛋白、SOX-2以及Musashi1和 -2。在相同标本中,免疫组织化学双重染色后进行共聚焦分析显示,Musashi2始终与增殖标志物Ki67共定位。相比之下,在任何对照标本中均未检测到此类基因或蛋白表达谱。因此,蛛网膜下腔出血后成人人类大脑中可能会发生神经祖细胞增殖的激活,这在这种病理状况下可能有助于促进自发恢复。