title: Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke.
abstract: The functional role of reactive astrocytes after stroke is controversial. To elucidate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST), and the spatio-temporal change of chondroitin sulfate proteoglycan (CSPG) expression between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP(-/-) Vim(-/-) ) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the CST axons. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP(-/-) Vim(-/-) mice (n = 10/group, P < 0.01). Immunohistological data showed that in GFAP(-/-) Vim(-/-) mice, in which astrocytic reactivity is attenuated, CSPG expression was significantly increased in the lesion remote areas in both hemispheres, but decreased in the ischemic lesion boundary zone, compared with WT mice (n = 12/group, P < 0.001). Our data suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord. Thus, manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Cui
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wilhelmsson
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001710:Biotin / Q000031:analogs & derivatives; D020520:Brain Infarction / Q000209:etiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009069:Movement Disorders / Q000209:etiology; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011712:Pyramidal Tracts / Q000473:pathology; D020127:Recovery of Function / Q000235:genetics*; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology*; D013927:Thrombosis / Q000209:etiology; D053675:Versicans / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C508323:Vcan protein, mouse; D014746:Vimentin; C076397:biotinylated dextran amine; D053675:Versicans; D001710:Biotin
keywords: axonal remodeling; glial scar; reactive astrocytes; stroke recovery