title: Extract derived from rat brains in the acute phase following traumatic brain injury impairs survival of undifferentiated stem cells and induces rapid differentiation of surviving cells.
abstract: Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and/or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro. Rats were sacrificed at t = 45 minutes following lateral fluid-percussion injury and extracts of cerebral tissue were prepared from 4-6 healthy or injured rat brain hemispheres. Murine embryonic stem cells (CGR8) cultured in serum-free medium were then conditioned for a week with HBE or TBE. Omission of serum from the culture medium induced neural differentiation of CGR8 stem cells, as indicated by a significant time dependent down-regulation of oct-4 with a concomitant upregulation of nestin after 7 days. In parallel cell loss was observed that seemed to be largely due to apoptotic cell death. In TBE treated cells, on the other hand, a significant amplification of apoptotic cell death, enhancement of nestin and MAP2 expression and marked morphological changes such as axonal-like outgrowth was observed within 3 days of conditioning. Treatment of stem cells with HBE resulted in less pronounced neuronal differentiation processes. Axonal-like outgrowth was not observed. Our data suggest that during the early acute phase of traumatic injury the cerebral environment is disposed to detrimental as well as potent protective signals that seem to rapidly induce neurogenic processes.
authors.affiliation: Videnregion, Syddanskuniversitet, University of Cologne, Germany.
authors.forename: Kristine
authors.initials: K
authors.lastname: Bentz
authors.forename: Marek
authors.initials: M
authors.lastname: Molcanyi
authors.forename: Annette
authors.initials: A
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Riess
authors.forename: Marc
authors.initials: M
authors.lastname: Maegele
authors.forename: Bert
authors.initials: B
authors.lastname: Bosche
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Hampl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Silke
authors.initials: S
authors.lastname: Patz
authors.forename: Ute
authors.initials: U
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D050814:Octamer Transcription Factor-3