title: Caspase inhibition impaired the neural stem/progenitor cell response after cortical ischemia in mice.
abstract: Cortical ischemia induces proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) and provokes migration of these cells toward the injured area. Despite sustained migration of NSPCs for an extended period of time after injury, they do not appear to survive. Here, we hypothesized that the anti-apoptotic broad-spectrum caspase inhibitor Q-VD-OPh would increase NSPC survival in the injured cortex. However, contrary to our expectations, caspase inhibition did not promote NSPC survival and cortical neurogenesis. On the contrary, it abolished ischemia-induced proliferation and decreased the number of migrating neuroblasts in the injured cortex. Moreover, caspase inhibition decreased the levels of the chemoattractant chemokine CCL2 (MCP-1) and the pro-inflammatory cytokine IL-1β. We hence for the first time show that caspase inhibition abrogates the response of NSPCs to an ischemic injury, presumably by inhibiting the production of pro-inflammatory factors. Thus, caution is warranted if anti-apoptotic strategies are applied for neuroprotection.
authors.affiliation: Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Osman
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: H Georg
authors.initials: HG
authors.lastname: Kuhn
authors.affiliation: Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D061945:Caspase Inhibitors / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D011804:Quinolines; C468548:quinoline-val-asp(OMe)-CH2-OPH; D020169:Caspases
keywords: Q-VD-OPh; migration; neurogenesis; neuroinflammation; stroke