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Postacute stromal cell-derived factor-1α expression promotes neurovascular recovery in ischemic mice.
Li, Yaning; Huang, Jun; He, Xiaosong; Tang, Guanghui; Tang, Yao-Hui; Liu, Yanqun; Lin, Xiaojie; Lu, Yifan; Yang, Guo-Yuan; Wang, Yongting.
Afiliación
  • Li Y; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Huang J; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • He X; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Tang G; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Tang YH; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Liu Y; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Lin X; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Lu Y; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Yang GY; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
  • Wang Y; From the Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering (Y.L., J.H., X.H., G.T., Y.-H.T., X.L., Y. Lu, G.-Y.Y., Y.W.) and Department of Neurology, Ruijin Hospital, School of Medicine (Y. Liu, G.-Y.Y.), Shanghai Jiao Tong University, S
Stroke ; 45(6): 1822-9, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24876262
ABSTRACT
BACKGROUND AND

PURPOSE:

Acute interventions of stroke are often challenged by a narrow treatment window. In this study, we explore treatments in the postacute phase of stroke with wider windows of opportunity. We investigated the effects of stromal cell-derived factor (SDF-1α) in neurovascular recovery during the postacute phase and downstream signaling pathways, underlying SDF-1α-mediated neurovascular recovery.

METHODS:

Adult male Institute of Cancer Research (ICR) mice underwent middle cerebral artery occlusion. One week after middle cerebral artery occlusion, the animals received stereotactic injection of adenoassociated virus (AAV) carrying SDF-1α gene as treatment or AAV-green fluorescent protein as control and were monitored for 5 weeks. Neurobehavioral outcomes were evaluated, and brain atrophy was measured. Neurogenesis and angiogenesis were examined. The proliferation and migration of neural progenitor cells were evaluated. Downstream pathways of SDF-1α were investigated. Inflammatory response was monitored.

RESULTS:

Neurobehavioral outcomes were improved, and brain atrophy was greatly reduced for ≤5 weeks in AAV-SDF-1α groups when compared with the control. SDF-1 receptor CXCR4 was upregulated and colocalized with neural and endothelial progenitor cells. The number of nestin(+) and doublecortin(+)/bromodeoxyuridine(+) cells in the subventricular zone, doublecortin(+) and neuron(+)/bromodeoxyuridine(+) cells in the perifocal region, and cluster of differentiation (CD)31(+) and bromodeoxyuridine(+)/CD31(+) microvessels are also significantly increased in AAV-SDF-1α groups. Administration of CXCR4 antagonist AMD3100 eliminated the beneficial effects of SDF-1α. SDF-1α/CXCR4 interaction activated AKT, extracellular signal-regulated kinases (ERK), and P38 mitogen-activated protein kinase (MAPK) signaling pathways but not the c-Jun N-terminal kinase (JNK) pathway.

CONCLUSIONS:

SDF-1α promoted neurogenesis and angiogenesis during the postacute phase of ischemia without eliciting an inflammatory response. AAV-SDF-1α expression represents a promising avenue for ischemic stroke therapy with a wider treatment window.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Terapia Genética / Regulación de la Expresión Génica / Neovascularización Fisiológica / Infarto de la Arteria Cerebral Media / Quimiocina CXCL12 / Neurogénesis Límite: Animals Idioma: En Revista: Stroke Año: 2014 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Terapia Genética / Regulación de la Expresión Génica / Neovascularización Fisiológica / Infarto de la Arteria Cerebral Media / Quimiocina CXCL12 / Neurogénesis Límite: Animals Idioma: En Revista: Stroke Año: 2014 Tipo del documento: Article