1. Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke.
- Author
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Chapman KZ, Ge R, Monni E, Tatarishvili J, Ahlenius H, Arvidsson A, Ekdahl CT, Lindvall O, and Kokaia Z
- Subjects
- Animals, Cell Death, Cell Movement drug effects, Chemokine CXCL13 pharmacology, Chemokine CXCL13 physiology, Corpus Striatum metabolism, Corpus Striatum pathology, Doublecortin Protein, Encephalitis chemically induced, Encephalitis metabolism, Gene Expression, Infarction, Middle Cerebral Artery pathology, Inflammation Mediators metabolism, Lateral Ventricles cytology, Lateral Ventricles metabolism, Lateral Ventricles physiopathology, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia cytology, Microglia metabolism, Neurons pathology, Rats, Rats, Wistar, Receptors, CXCR5 genetics, Receptors, CXCR5 physiology, Stroke pathology, Corpus Striatum physiopathology, Encephalitis physiopathology, Infarction, Middle Cerebral Artery physiopathology, Neural Stem Cells physiology, Neurogenesis, Neurons physiology, Stroke physiopathology
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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