title: Conditioned Medium Derived from Neural Progenitor Cells Induces Long-term Post-ischemic Neuroprotection, Sustained Neurological Recovery, Neurogenesis, and Angiogenesis.
abstract: Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity-promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia and intravenously applied conditioned medium (CM) derived from subventricular zone NPCs. CM dose-dependently reduced infarct volume and brain leukocyte infiltration after 48 h when delivered up to 12 h after focal cerebral ischemia. Neuroprotection persisted in the post-acute stroke phase yielding enhanced neurological recovery that lasted throughout the 28-day observation period. Increased Bcl-2, phosphorylated Akt and phosphorylated STAT-3 abundance, and reduced caspase-3 activity and Bax abundance were noted in ischemic brains of CM-treated mice at 48 h post-stroke, indicative of enhanced cell survival signaling. Long-term neuroprotection was associated with increased brain glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) concentrations at 28 days resulting in increased neurogenesis and angiogenesis. The observation that NPC-derived CM induces sustained neuroprotection and neurological recovery suggests that cell transplantation may be dispensable when secreted factors are instead administered.
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany. thorsten.doeppner@uk-essen.de.|Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey. thorsten.doeppner@uk-essen.de.|Department of Neurology, University of Göttingen Medical School, Göttingen, Germany. thorsten.doeppner@uk-essen.de.
authors: Thorsten R
authors: TR
authors: Doeppner
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany.
authors: Viktorija
authors: V
authors: Traut
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany.
authors: Alexander
authors: A
authors: Heidenreich
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany.
authors: Britta
authors: B
authors: Kaltwasser
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany.|Department of Surgery, Division of Neurosurgery, St Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors: Bert
authors: B
authors: Bosche
authors: Department of Neurology, University of Göttingen Medical School, Göttingen, Germany.
authors: Mathias
authors: M
authors: Bähr
authors: Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany.
authors: Dirk M
authors: DM
authors: Hermann
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned
keywords: Cerebral ischemia; Conditioned medium; Neural progenitor cells; Neuroregeneration; Stroke