Post-ischemic treatment with TC reduced infarct size by 53.8% and reduced edema by 51.9%. However, co-administration of the CB2R antagonist AM630 completely blocked the protective effect of TC. Further analysis indicated that CB2R activation is involved in the ability of TC to induce cAMP responsive element-binding protein (CREB) phosphorylation and increase the expression of brain-derived neurotrophic factor (BDNF) in ischemic tissue.
Cell-culture studies of embryonic rat cortical neurons and glia exposed to OGD/R to simulate ischemic insult confirmed some of the findings of the in vivo studies and contributed to further understanding about cellular effects of ischemia and TC treatment. In the cultures, TC decreased neuronal injury, intracellular oxidative stress, and mitochondrial depolarization following OGD/R, and the effects were reversed by AM630 but not by a CB1R antagonist, AM251. Western blot analysis demonstrated that TC enhanced the phosphorylation of AMP protein kinase (AMPK) and CREB, while selective AMPK and CREB inhibitors blocked TC's neuroprotection. Other findings indicated that the anti-ischemic effect of TC was not mediated by NMDA receptor antagonism or antioxidant activity.
TC is a major cannabinoid derived from the essential oil of the flowering plant Cannabis sativa, but has a fundamentally different structure from classical cannabinoids. Unlike agents which activate CB1 receptors, selective CB2R receptor agonists do not have psychoactive side effects. TC appears to maintain CB2R agonist activity when administered orally and is a common ingredient found in many food additives and folk medicines. The intriguing results of the present study suggest that the anti-ischemic benefits of TC deserve further exploration.
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Elsevier Health Sciences