The effect of δ-9-tetrahydrocannabinol on forebrain ischemia in rat

Role of Cannabinoids and Endocannabinoids in Cerebral Ischemia

“…Interestingly, the protective effect was reversed by co-administration of Win 55212-2, supporting a role for the CB1 receptor in this effect of rimonabant. In another study, chronic treatment of rats with THC for 7 days at doses known to reduce CB1 receptor mRNA expression in the striatum but not the hippocampus [105] resulted in a significant reduction in ischemic injury in the striatum but not hippocampus [106]. The degree of protection in the striatum was remarkable, particularly since this brain region is notoriously insensitive to protective interventions.…”

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…Surprisingly, all protection could be abolished by warming the animals to the body temperature of controls, indicating that CB 1 -mediated hypothermia contributed to the neuroprotection . Likewise, CB 1 -mediated hypothermia was responsible for the neuroprotective effects of THC in a mouse transient MCAo model (Hayakawa et al, 2004) and perhaps also in a rat model of global cerebral ischemia (Louw et al, 2000). Consistent with these findings, CB 1 knockout mice had increased mortality from permanent focal cerebral ischemia, increased infarct size, more severe neurological deficits after transient focal cerebral ischemia, and decreased cerebral blood flow in the ischemic penumbra during reperfusion, compared with wild type controls subjected to the same insult (Parmentier-Batteur et al, 2002).…”

Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

“…CB 1 receptor expression was enhanced in the arterial boundary zone of the cortical mantle after a 20 min occlusion of the middle cerebral artery in rats (Jin et al, 2000). Chronic ∆ 9 -THC administration reduces the impact of an ischemic insult evoked by lowering blood pressure and 12 min bilateral carotid artery occlusion (Louw et al, 2000). The mixed CB 1/ CB 2 cannabinoid receptor agonist WIN55,212-2 afforded protection to hippocampal and cortical neurons in CB 1 receptordependent manner in rats with a permanent middle cerebral artery occlusion or global ischemia (Nagayama et al, 1999).…”