Melatonin reduces infarction volume in a photothrombotic stroke model in the wild‐type but not cyclooxygenase‐1‐gene knockout mice

Journal of Pineal Research - Tập 41 Số 2 - Trang 150-156 - 2006
Liang Zou1, Raymond Tak Fai Cheung1, Sirun Liu2, Geng Li3, Li Huang2
1Division of Neurology, University Department of Medicine, The University of Hong Kong, Hong Kong
2Medical Imaging Centre, The First Affiliated Hospital of Medical College, Jinan University, Guangzhou, China
3The Jockey Club MRI Engineering Centre, Faculty of Medicine, The University of Hong Kong, Hong Kong

Tóm tắt

Abstract:  Cyclooxygenase (COX)‐2 plays a harmful role in cerebral ischemic/reperfusion injury, but the role of COX‐1 is uncertain. In the present study, cerebral infarct was induced by photothrombosis. Intraperitoneal injections of melatonin at 15 g/kg or its vehicle were made at 0.5 hr before stroke and 24 and 48 hr after stroke. Cerebral blood flow (CBF) in the penumbra was monitored during stroke using a laser Doppler flowmeter. Sensorimotor behavior was evaluated using the turning in an alley and falling from a pole tests at 1 hr before stroke and 24 and 48 hr after stroke. Infarct volume was determined from the T2‐weighted magnetic resonance images at 72 hr after stroke. During the first 15 min of stroke, CBF decreased in the penumbra in both homozygous COX‐1‐gene knockout and wild‐type mice. Melatonin treatment improved the penumbral CBF in the wild‐type mice. Mild poststroke impairment in sensorimotor behavior was detected by the turning in an alley test in which the COX‐1‐gene knockout mice performed better. Melatonin treatment did not affect the poststroke sensorimotor behavior. The relative infarct volume at 72 hr after stroke was 8.1% and 8.4% in the COX‐1‐gene knockout and wild‐type mice, respectively. Melatonin treatment reduced the relative infarct volume to 6.3% in the latter but not in the former (8.2%). Thus, COX‐1‐gene knockout does not affect the brain's susceptibility to photothrombotic stroke. Melatonin treatment reduces infarct size in the wild‐type mice following photothrombotic stroke partly via maintenance of penumbral CBF in which the COX‐1‐gene may play a role.

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