title: Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke.
abstract: Ischemic stroke triggers neurogenesis from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) and migration of newly formed neuroblasts toward the damaged striatum where they differentiate to mature neurons. Whether it is the injury per se or the associated inflammation that gives rise to this endogenous neurogenic response is unknown. Here we showed that inflammation without corresponding neuronal loss caused by intrastriatal lipopolysaccharide (LPS) injection leads to striatal neurogenesis in rats comparable to that after a 30 min middle cerebral artery occlusion, as characterized by striatal DCX+ neuroblast recruitment and mature NeuN+/BrdU+ neuron formation. Using global gene expression analysis, changes in several factors that could potentially regulate striatal neurogenesis were identified in microglia sorted from SVZ and striatum of LPS-injected and stroke-subjected rats. Among the upregulated factors, one chemokine, CXCL13, was found to promote neuroblast migration from neonatal mouse SVZ explants in vitro. However, neuroblast migration to the striatum was not affected in constitutive CXCL13 receptor CXCR5(-/-) mice subjected to stroke. Infarct volume and pro-inflammatory M1 microglia/macrophage density were increased in CXCR5(-/-) mice, suggesting that microglia-derived CXCL13, acting through CXCR5, might be involved in neuroprotection following stroke. Our findings raise the possibility that the inflammation accompanying an ischemic insult is the major inducer of striatal neurogenesis after stroke.
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Katie Z
authors: KZ
authors: Chapman
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Ruimin
authors: R
authors: Ge
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Emanuela
authors: E
authors: Monni
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Jemal
authors: J
authors: Tatarishvili
authors: Stem cells, Aging and Neurodegeneration Group, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Henrik
authors: H
authors: Ahlenius
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden; Division of Neurology, University Hospital, SE-221 84 Lund, Sweden.
authors: Andreas
authors: A
authors: Arvidsson
authors: Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Christine T
authors: CT
authors: Ekdahl
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors: Olle
authors: O
authors: Lindvall
authors: Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden. Electronic address: zaal.kokaia@med.lu.se.
authors: Zaal
authors: Z
authors: Kokaia
mesh_terms: D000818:Animals; D016923:Cell Death; D002465:Cell Movement / Q000187:drug effects; D054382:Chemokine CXCL13 / Q000494:pharmacology / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000089662:Doublecortin Protein; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D054380:Receptors, CXCR5 / Q000235:genetics / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
chemical_list: C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D054380:Receptors, CXCR5
keywords: CXCL13; CXCR5; Inflammation; Lipopolysaccharide; Microarray; Microglia; Neurogenesis; Striatum; Stroke