PMID- 23383048 OWN - NLM STAT- MEDLINE DCOM- 20130719 LR - 20231213 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum. PG - e55039 LID - 10.1371/journal.pone.0055039 [doi] LID - e55039 AB - Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. FAU - Grade, Sofia AU - Grade S AD - Cellular Neurobiology Unit, Insitut en Sante Mentale de Quebec, Quebec City, Canada. FAU - Weng, Yuan C AU - Weng YC FAU - Snapyan, Marina AU - Snapyan M FAU - Kriz, Jasna AU - Kriz J FAU - Malva, Joao O AU - Malva JO FAU - Saghatelyan, Armen AU - Saghatelyan A LA - eng GR - 110947/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130129 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - 0 (Ngfr protein, mouse) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Astrocytes/metabolism/pathology MH - Brain Ischemia/genetics/metabolism/*pathology/*physiopathology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - *Cell Movement MH - Gene Expression Regulation MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neostriatum/*blood supply/*pathology MH - Neovascularization, Physiologic MH - Neural Stem Cells/pathology MH - Neurons/metabolism/*pathology MH - Receptor, trkB/genetics MH - Receptors, Nerve Growth Factor/genetics PMC - PMC3558494 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/02/06 06:00 MHDA- 2013/07/20 06:00 PMCR- 2013/01/29 CRDT- 2013/02/06 06:00 PHST- 2012/09/19 00:00 [received] PHST- 2012/12/17 00:00 [accepted] PHST- 2013/02/06 06:00 [entrez] PHST- 2013/02/06 06:00 [pubmed] PHST- 2013/07/20 06:00 [medline] PHST- 2013/01/29 00:00 [pmc-release] AID - PONE-D-12-28491 [pii] AID - 10.1371/journal.pone.0055039 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e55039. doi: 10.1371/journal.pone.0055039. Epub 2013 Jan 29.