Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice
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Updated: Aug 6, 2026
Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies
Published on: June 9, 2013
Liang Yu Zou1, Raymond Tak Fai Cheung, Sirun Liu
1Division of Neurology, University Department of Medicine, The University of Hong Kong, Hong Kong.
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.
Insights
Melatonin reduces stroke-induced brain damage in wild-type mice by maintaining blood flow, suggesting cyclooxygenase-1 (COX-1) plays a role. COX-1 gene knockout did not alter stroke susceptibility or melatonin
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cyclooxygenase (COX)-2 is implicated in harmful cerebral ischemic/reperfusion injury.
- The specific role of cyclooxygenase (COX)-1 in this injury remains unclear.
Purpose of the Study:
- To investigate the role of COX-1 in cerebral infarct development.
- To determine the effect of melatonin on cerebral blood flow and infarct size in a stroke model.
Main Methods:
- Cerebral infarct was induced using photothrombosis in mice.
- Mice received melatonin injections before and after stroke induction.
- Cerebral blood flow (CBF), sensorimotor behavior, and infarct volume were assessed.
Main Results:
- Melatonin improved penumbral CBF in wild-type mice but not in COX-1 gene knockout mice.
- COX-1 gene knockout mice showed mild poststroke sensorimotor impairment.
- Melatonin significantly reduced infarct volume in wild-type mice but not in COX-1 gene knockout mice.
Conclusions:
- COX-1 gene knockout does not affect susceptibility to photothrombotic stroke.
- Melatonin reduces infarct size in wild-type mice, partly by maintaining penumbral CBF.
- COX-1 appears to play a role in the protective effects of melatonin against cerebral ischemia.
