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Beneficial Effects of GFAP/Vimentin Reactive Astrocytes for Axonal Remodeling and Motor Behavioral Recovery in Mice after Stroke

Journal article
Authors Z. W. Liu
Y. Li
Y. S. Cui
C. Roberts
M. Lu
Ulrika Wilhelmsson
Milos Pekny
M. Chopp
Published in Glia
Volume 62
Issue 12
Pages 2022-2033
ISSN 0894-1491
Publication year 2014
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 2022-2033
Language en
Links dx.doi.org/10.1002/glia.22723
Keywords reactive astrocytes, axonal remodeling, stroke recovery, glial scar, CENTRAL-NERVOUS-SYSTEM, FIBRILLARY ACIDIC PROTEIN, SPINAL-CORD-INJURY, CHONDROITIN SULFATE PROTEOGLYCAN, MARROW STROMAL CELL, INTERMEDIATE-FILAMENTS, NEURITE OUTGROWTH, CEREBRAL-ISCHEMIA, FUNCTIONAL, RECOVERY, CNS INJURY, Neurosciences
Subject categories Neuroscience

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. GLIA 2014;62:2022-2033 Post stroke, GFAP/Vimentin knockout mice with attenuated gliosis have reduced or slower neurological recovery and corticospinal remodeling, and increased chondroitin sulfate proteoglycan expression, suggesting that reactive astrocytes promote recovery.

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