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Acta neurochirurgica · Jul 2013
Intraperitoneal treatment with S100B enhances hippocampal neurogenesis in juvenile mice and after experimental brain injury.
- Andrea Kleindienst, Felicitas Grünbeck, Rolf Buslei, Irene Emtmann, and Michael Buchfelder.
- Departments of Neurosurgery and Neuropathology, Friedrich-Alexander University of Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. andrea.kleindienst@uk-erlangen.de
- Acta Neurochir (Wien). 2013 Jul 1;155(7):1351-60.
BackgroundNeurogenesis 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.MethodsMale 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.ResultsS100B 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.ConclusionWe 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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