Adult neurogenesis in the human central nervous system in response to stroke - an investigation using the novel methodology of retrospective radiocarbon-based birth dating of cells

与长期以来的看法相反，即使在成年期，在人类中枢神经系统的某些区域，特别是海马体，新的神经元也会从神经干细胞中不断产生。这一发现提出了一种可能性，即休眠的神经干细胞也可能存在于成年人大脑的许多其他区域，并在神经疾病和创伤，特别是中风时被激活。最近，开发了一种基于放射性碳的追溯细胞出生年代的巧妙方法，该方法利用了冷战期间地面核弹试验导致的14C水平的急剧变化，并允许通过加速器质谱法确定细胞中DNA的年龄。在这里，它建议应用这种新的方法来明确回答的问题（i）是否存在于健康的成年人大脑的其他区域的神经发生，以及（ii）是否成人神经发生诱导神经创伤和疾病，特别是中风。一个重要的方面，拟议的调查将涉及成人神经发生的个别病例的临床病史的数据，以确定是否成人神经发生有助于功能恢复。进一步提出通过分析人脑脊液中的膜囊泡来探索成体神经干细胞和其他具有神经前体潜能的细胞的可能活化来补充这些研究，这是申请人最近验证的一种新方法。该项目的最终目标是使用新颖和创新的方法，在具有医学意义的情况下，建立人类中枢神经系统生理学和病理学的细胞更新图，从而为再生疗法的发展提供基本信息。

Contrary to a long-lasting belief, new neurons are continuously generated from neural stem cells even during adulthood in certain regions of the human central nervous sytem, notably the hippocampus. This discovery of adult neurogenesis raises the possibility that dormant neural stem cells may exist in many other regions of the adult human brain as well, and be activated in response to neural disease and trauma, in particular stroke. Recently, an ingenious method of retrospective radiocarbon-based birth dating of cells has been developed, which takes advantage of the drastically altered 14C levels due to above-ground nuclear bomb testing during the Cold War and allows the determination of the age of DNA in cells by accelerator mass spectrometry. Here, it is proposed to apply this novel methodology to unequivocally answer the questions (i) whether neurogenesis exists in other regions of the healthy adult human brain, and (ii) whether adult neurogenesis is induced in response to neurological trauma and disease, notably stroke. An important aspect of the proposed investigations will be to relate the data obtained on adult neurogenesis to the clinical history of the individual cases, in order to determine whether adult neurogenesis contributes to functional recovery. It is further proposed to complement these studies by exploring the possible activation of adult neural stem cells and other cells with neural precursor potential via analysis of membrane vesicles in human cerebrospinal fluid, a novel approach recently validated by the applicant. The ultimate goal of the project is to establish a map of cell renewal in physiology and pathology in the human central nervous system in situations of medical interest using novel and innovative methodology, thereby contributing basic information for the development of regenerative therapies.