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

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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.