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Open Access Highly Accessed Research article

Contribution of constitutively proliferating precursor cell subtypes to dentate neurogenesis after cortical infarcts

Silke Keiner, Josephine Walter, Julia Oberland and Christoph Redecker*

Author Affiliations

Hans-Berger-Clinic for Neurology, University Hospital Jena, Erlanger Allee 101, D - 07747 Jena, Germany

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BMC Neuroscience 2010, 11:146  doi:10.1186/1471-2202-11-146

Published: 17 November 2010

Abstract

Background

It is well known that focal ischemia increases neurogenesis in the adult dentate gyrus of the hippocampal formation but the cellular mechanisms underlying this proliferative response are only poorly understood. We here investigated whether precursor cells which constitutively proliferate before the ischemic infarct contribute to post-ischemic neurogenesis. To this purpose, transgenic mice expressing green fluorescent protein (GFP) under the control of the nestin promoter received repetitive injections of the proliferation marker bromodeoxyuridine (BrdU) prior to induction of cortical infarcts. We then immunocytochemically analyzed the fate of these BrdU-positive precursor cell subtypes from day 4 to day 28 after the lesion.

Results

Quantification of BrdU-expressing precursor cell populations revealed no alteration in number of radial glia-like type 1 cells but a sequential increase of later precursor cell subtypes in lesioned animals (type 2a cells at day 7, type 3 cells/immature neurons at day 14). These alterations result in an enhanced survival of mature neurons 4 weeks postinfarct.

Conclusions

Focal cortical infarcts recruit dentate precursor cells generated already before the infarct and significantly contribute to an enhanced neurogenesis. Our findings thereby increase our understanding of the complex cellular mechanisms of postlesional neurogenesis.