Role of the endogenous cannabinoid receptor 1 in brain injury induced by chronic intermittent hypoxia in rats

ABSTRACT Purpose: This study investigated the effect of rimonabant, a cannabinoid receptor type 1 antagonist, on calcium/calmodulin- dependent protein kinase II and cannabinoid receptor type 1 in chronic intermittent hypoxia. Materials and methods: Healthy male rats were divided into control group, intermittent hypoxia group for 4 or 6 weeks, hypoxic intervention group that received rimonabant (1 mg/kg/d) before exposure to hypoxia for 4 or 6 weeks (n = 10/group). Morphological changes and expressions of the two indexes in the cerebral hippocampus cells were determined by haematoxylin–eosin staining and immunohistochemistry, respectively. Results: In the intermittent hypoxia group at 4 weeks, the hippocampal cells were damaged with sparse cytoplasm and unclear boundaries, which are even worse at 6 weeks. In contrast, the hippocampal cells of the hypoxic intervention group were neatly arranged at 4 weeks. At 6 weeks, cells were larger with scarce cytoplasm and nuclear changes indicative of cell death. Calcium/calmodulin-dependent protein kinase II and cannabinoid receptor type 1 expression in the cerebral hippocampus was elevated in the intermittent hypoxia group at 4 weeks with even greater at 6 weeks. Cannabinoid receptor type 1 expression was reduced in the hypoxic intervention group compared to the intermittent hypoxia group. Correlation analysis revealed significant positive correlation of them in the intermittent hypoxia group. Conclusions: Chronic intermittent hypoxia induced structural damage in the hippocampus and increased cannabinoid receptor type 1 and calcium/calmodulin-dependent protein kinase II expression, which may mediate cognitive impairment associated with chronic intermittent hypoxia. Rimonabant had a protective effect against chronic intermittent hypoxia.

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