Abstract
Background
Neurogenesis is documented in adult mammals including humans, is promoted by neurotrophic factors, and constitutes an innate repair mechanism following brain injury. The glial neurotrophic protein S100B is released following various types of brain injuries, enhances hippocampal neurogenesis and improves cognitive function following brain injury in rats when applied intrathecally. The present study was designed to elucidate whether the beneficial effect of S100B on injury-induced neurogenesis can be confirmed in mice when applied intraperitoneally (i.p.), and whether this effect is dose-dependent.
Methods
Male juvenile mice were subjected to a unilateral parietal cryolesion or sham injury, and treated with S100B at 20nM, 200nM or vehicle i.p. once daily. Hippocampal progenitor cell proliferation was quantified following labelling with bromo-deoxyuridine (BrdU, 50 mg/KG i.p.) in the germinative area of the dentate gyrus, the subgranular zone (SGZ), on day 4 as well as on cell survival and migration to the granular cell layer (GCL) on day 28. Progenitor cell differentiation was assessed following colabelling with the glial marker GFAP and the neuronal marker NeuN.
Results
S100B enhanced significantly the early progenitor cell proliferation in the SGZ as well as cell survival and migration to the GCL, and promoted neuronal differentiation. While these effects were predominately dose-dependent, 200nM S100B failed to enhance the proliferation in the SGZ on day 4 post-injury.
Conclusion
We conclude that S100B participates in hippocampal neurogenesis after injury at lower nanomolar concentrations. Therefore S100B may serve as a potential adjunct treatment to promote neuroregeneration following brain damage.
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Acknowledgments
These studies were supported in part by a Grant of the Section Neurosurgical Research, German Society of Neurosurgery (DGNC) and the Fond for Science and Education, Friedrich-Alexander-University Erlangen-Nürnberg Medical School (ELAN) to AK. None of the authors nor the academic institution or employer has any financial or ownership interest directly related to the topic of this manuscript.
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Kleindienst, A., Grünbeck, F., Buslei, R. et al. Intraperitoneal treatment with S100B enhances hippocampal neurogenesis in juvenile mice and after experimental brain injury. Acta Neurochir 155, 1351–1360 (2013). https://doi.org/10.1007/s00701-013-1720-2
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DOI: https://doi.org/10.1007/s00701-013-1720-2