期刊
STROKE
卷 47, 期 1, 页码 214-220出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.115.011046
关键词
axon; insulin-like growth factor-1; neuroinflammation; stroke; white matter
资金
- National Institute on Aging [R01 AG037506]
- National Institute of Neurological Disorders and Stroke [R01 NS083078, R01 NS092917]
- American Heart Association [14GRNT20460026, 12SDG9300009]
Background and Purpose Stroke-induced neuroinflammation and white matter damage are associated with neurological deficits. Whether D-4F, an apolipoprotein A-I mimetic peptide, treatment of stroke decreases neuroinflammation and white matter damage and improves functional outcome has not been investigated. Methods Adult male C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (MCAo) and were orally administered saline as a vehicle control and different doses of D-4F (2, 4, 8, 16, or 32 mg/kg) starting at 2 h after MCAo and daily until euthanized at 7 days after MCAo. D-4F treatment did not alter the blood levels of high-density lipoprotein, total cholesterol, triglyceride, blood-brain barrier leakage, and infarction volume compared with control group. Results D-4F (16 mg/kg) treatment of stroke significantly improved functional outcome, increased the white matter density and the number of oligodendrocyte progenitor cells in the ischemic boundary zone of the ipsilateral striatum, and increased myelin basic protein, insulin-like growth factor-1 (IGF1), but decreased inflammatory factor Toll-like receptor-4 and tumor necrosis factor- expression in the ischemic brain 7 days after MCAo (P<0.05, n=11/group). The neurite/axonal outgrowth in primary cultured neurons was significantly increased when treated with D-4F (100 ng/mL) and IGF1 (100 ng/mL) compared with the nontreatment control. Inhibition of IGF1 significantly attenuated D-4F or IGF1 treatment-induced axonal outgrowth. D-4F-treatment did not increase oligodendrocyte-progenitor cell proliferation but decreased oligodendrocyte-progenitor cell death. Conclusions D-4F treatment initiated 2 h after MCAo decreases neuroinflammation and white matter damage and improves functional outcome after stroke. D-4F-induced increase in IGF1 may contribute to D-4F-induced neurite/axonal outgrowth after stroke.
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