Investigating human adult neurogenesis within the basal ganglia in response to ischemic stroke using the radiocarbon-based technique of retrospective birth dating of neural cells.

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The applicant had received a DFG-stipend and investigated the existence of adult human neurogenesis in preliminary studies using the Radiocarbon-based technique of retrospective birth dating of neural cells. As a key finding there was evidence of lifelong continuous neurogenesis within the dentate gyrus of the hippocampus in the adult human brain which was age-dependent and amounted up to 2-6% per year (the applicant was coauthor of this study published 2013 in Cell). Further, the author was first author of a paper published 2014 in Nature Neuroscience that investigated neurogenesis after ischemic stroke. As a key finding there was confirmatory data that with the healthy cerebral cortex there is no adult neurogenesis. After ischemic stroke of the cerebral cortex there is no detectable induction and thus also no significant neurogenesis. Based on this preliminary work the present grant application focusses on the related two most relevant research questions. First, the proposed project will investigate whether there is human adult neurogenesis within the basal ganglia in response to ischemic stroke. Second, the applicant will study whether the continuous neurogenesis within the hippocampus is altered upon ischemic stroke of the basal ganglia or the cerebral cortex. Both, an increased rate of neurogenesis within the basal ganglia as well as within the ipsilateral hippocampus in response to ischemic stroke has been reported in rodents after experimental stroke. It appears of fundamental relevance to study whether these finding also hold true in man. Given the bulk of negative clinical studies regarding neuroprotection in the acute phase of ischemic stroke in humans (those trials predominantly investigated beneficial effects of drugs targeting on manipulation of the ischemic cascade), the proposed research project aims to provide information on the physiological and pathophysiological mechanisms that act in acute stroke and also on the long-term, possibly affecting functional recovery. This will help to understand if neurogenesis occurs and is altered upon ischemic stroke and, if so, whether neurogenesis has a functional relevance. The obtained results may have clinical implications such that a meaningful translation of preclinical studies to successful clinical trials can be achieved.