title: Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.
abstract: Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.
authors: Center for Neuropsychiatric Research, National Health Research Institute, Zhunan, Taiwan ; Neural Protection and Regeneration Section, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, United States of America.
authors: Seong-Jin
authors: SJ
authors: Yu
authors: Kuan-Yin
authors: KY
authors: Tseng
authors: Hui
authors: H
authors: Shen
authors: Brandon K
authors: BK
authors: Harvey
authors: Mikko
authors: M
authors: Airavaara
authors: Yun
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics*; D020521:Stroke / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor