Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke

Document Type

Article

Abstract

Promoting neural regeneration after cerebral infarction has emerged as a potential approach for the treatment of stroke. Insulin-like growth factor 1 (IGF-1) possesses both neurotrophic and angiogenic properties. The aim of this study was to determine whether postischemic gene transfer of IGF-1 enhances neurovascular regeneration in a mouse model of permanent focal cerebral ischemia. Long-term cerebral IGF-1 overexpression was achieved with adeno-associated viral vector (AAV) by stereotaxic injection at 24 h after a stroke. Adeno-associated viral vector-green fluorescent protein (GFP) or saline was injected as a control. The success of postischemic gene transduction was confirmed by a strong GFP signal and by increased IGF-1 protein expression in the peri-infarct region. Postischemic gene transfer of IGF-1 significantly enhanced vascular density at 8 weeks after a stroke in the peri-infarct and injection needle tract area compared with AAV-GFP or saline treatment, as shown by immunohistochemical staining with the vascular marker lectin. Furthermore, increased vascular density was associated with improved local vascular perfusion. Immunohistochemical staining with the neuronal progenitor marker, DCX (doublecortin), and the cell proliferation marker, BrdU (5-bromo-2-deoxyuridine-5-monophosphate), indicated that AAV-IGF-1 treatment potently increased neurogenesis compared with AAV-GFP injection. These data show that postischemic treatment of IGF-1 effectively promoted neural and vascular regeneration in the chronic stage of cerebral infarction.

Medical Subject Headings

Animals; Brain Ischemia (metabolism, pathology, therapy); Cerebrovascular Circulation (physiology); Doublecortin Protein; Gene Transfer Techniques; Genetic Therapy (methods); Genetic Vectors (genetics, metabolism); Humans; Insulin-Like Growth Factor I (genetics, metabolism); Mice; Microcirculation; Neovascularization, Physiologic (physiology); Regional Blood Flow (physiology); Transduction, Genetic

Publication Date

9-1-2009

Publication Title

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

E-ISSN

1559-7016

Volume

29

Issue

9

First Page

1528

Last Page

37

PubMed ID

19513085

Digital Object Identifier (DOI)

10.1038/jcbfm.2009.75

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