title: Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.
abstract: Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke.
authors: Laboratory of Experimental Neuroprotection and Neuroregeneration, Institute of Biological Sciences, Federal University of Para (UFPA), Belem, Brazil.
authors: Rosana S
authors: RS
authors: Lopes
authors: Marcelo M
authors: MM
authors: Cardoso
authors: Arthur O
authors: AO
authors: Sampaio
authors: Mario Santos
authors: MS
authors: Barbosa
authors: Celice C
authors: CC
authors: Souza
authors: Michelle C
authors: MC
authors: DA Silva
authors: Elane Magno N
authors: EM
authors: Ferreira
authors: Marco Aurelio M
authors: MA
authors: Freire
authors: Rafael Rodrigues
authors: RR
authors: Lima
authors: Walace
authors: W
authors: Gomes-Leal
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D000089662:Doublecortin Protein; D019332:Endothelin-1 / Q000633:toxicity; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D020521:Stroke / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019332:Endothelin-1; D007213:Indomethacin