Journal Article

Monocyte Chemoattractant Protein-1 Plays a Critical Role in Neuroblast Migration after Focal Cerebral Ischemia

Dempsey, Robert J, Sailor, Kurt A, Park, Seung-Won, Vemuganti, Raghu, Lang, Bradley T, Yan, Yi-Ping

2007

Overview

Transient focal ischemia is known to induce proliferation of neural progenitors in adult rodent brain. We presently report that doublecortin positive neuroblasts formed in the subventricular zone (SVZ) and the posterior peri-ventricle region migrate towards the cortical and striatal penumbra after transient middle cerebral artery occlusion (MCAO) in adult rodents. Cultured neural progenitor cells grafted into the non-infarcted area of the ipsilateral cortex migrated preferentially towards the infarct. As chemokines are known to induce cell migration, we investigated if monocyte chemoattractant protein-1 (MCP-1) has a role in post-ischemic neuroblast migration. Transient MCAO induced an increased expression of MCP-1 mRNA in the ipsilateral cortex and striatum. Immunostaining showed that the expression of MCP-1 was localized in the activated microglia and astrocytes present in the ischemic areas between days 1 and 3 of reperfusion. Furthermore, infusion of MCP-1 into the normal striatum induced neuroblast migration to the infusion site. The migrating neuroblasts expressed the MCP-1 receptor CCR2. In knockout mice that lacked either MCP-1 or its receptor CCR2, there was a significant decrease in the number of migrating neuroblasts from the ipsilateral SVZ to the ischemic striatum. These results show that MCP-1 is one of the factors that attract the migration of newly formed neuroblasts from neurogenic regions to the damaged regions of brain after focal ischemia.

• Publisher: SAGE Publications,Lippincott Williams & Wilkins,Sage Publications Ltd
• Subject: Animals / Biological and medical sciences / Brain Ischemia - pathology / Cell Movement / Cell Proliferation / Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges / Chemokine CCL2 - genetics / Chemokine CCL2 - physiology / Fundamental and applied biological sciences. Psychology / Infarction, Middle Cerebral Artery / Medical sciences / Mice / Mice, Knockout / Neurology / Neurons - cytology / Neurons - physiology / Neuropharmacology / Neuroprotective agent / Pharmacology. Drug treatments / Rats / Receptors, CCR2 / Receptors, Chemokine - analysis / RNA, Messenger - analysis / Up-Regulation / Vascular diseases and vascular malformations of the nervous system / Vertebrates: nervous system and sense organs