Therapeutic hypothermia is a robust therapeutic tool in experimental stroke models but its clinical applications
are limited. Furthermore, optimal conditions for therapeutic hypothermia, such as, temperature and the initiation and
duration of cooling must be individualized. Here, we evaluated the therapeutic effects of delayed local hypothermia,
administered for 44 hr after 4 hr of reperfusion in a rat model of transient middle cerebral artery occlusion (tMCAo), using
a cooling device that allowed controlled local hypothermia (31°C) in brain. Histological data revealed that local
hypothermia significantly reduced infarct volumes and glial hypertrophic activation. Brain water contents, IgG leakage,
and Evans Blue extravasation were notably reduced by local hypothermia. Furthermore, local hypothermia had strong
vasculoprotective effects, as determined by immunohistochemistry and Western blot analyses for endothelial barrier
antigen (EBA), laminin, aquaporin-4, and tight junction proteins in brain. Our data indicate that delayed/prolonged local
hypothermia confers neurovascular protection, reduces brain edema, and inhibits inflammatory glial activation, and
suggest that hypothermic conservation of vascular structures and functions account for the therapeutic effects of local
hypothermia observed in this model of experimental stroke.
Blood-brain barrier, edema, glia, local hypothermia, stroke, vascular protection
Department of Pharmacology, Kyungpook National University School of Medicine, 101 Dong-In, Joonggu, Daegu, 700-422, Korea.