Role of Cannabinoids and Endocannabinoids in Cerebral Ischemia

Abstract

The human costs of stroke are very large and growing; it is the third largest cause of death in the United States and survivors are often faced with loss of ability to function independently. There is a large need for therapeutic approaches that act to protect neurons from the injury produced by ischemia and reperfusion. The goal of this review is to introduce and discuss the available data that endogenous cannabinoid signaling is altered during ischemia and that it contributes to the consequences of ischemia-induced injury. Overall, the available data suggest that inhibition of CB1 receptor activation together with increased CB2 receptor activation produces beneficial effects.

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

“…4,5 Cannabinoids have anti-inflammatory effects and provide protection from ischemia/reperfusion injury. [6][7][8][9][10] Since pain is a manifestation of complex sickle pathobiology including inflammation, vascular dysfunction and ischemia/reperfusion injury, we investigated cannabinoid receptor-specific modulation of vascular function, inflammation and hyperalgesia.…”

5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia

“…Furthermore, ischemia reperfusion is commonly accompanied by edema formation in the brain. A reduction in the degree of edema formation following ischemia is beneficial to the outcome of the injury (Hillard 2008). Thereafter, we evaluated the water contents of brain in mice with or without 5-HMF treatment.…”

Cannabinoid Type-2 Receptor Drives Neurogenesis and Improves Functional Outcome After Stroke

“…В этом смысле эндоканнабиноидная система может быть перспективным кандидатом, учитывая ее четко установленную защитную роль при различной патологии головного мозга [15][16][17][18][19] и данные о ее способ-ности модулировать пролиферацию нейральных стволо-вых клеток [20,21], а также миграцию нейробластов in vitro и ex vivo [22] в физиологических условиях. Наиболее значимыми каннабиноидными рецепторами являются каннабиноидный рецептор 1-го типа (CB1R), в основном экспрессируемый нейронами [23], и каннабиноидный рецептор 2-го типа (CB2R), главным образом, располо-женный на клетках микроглии и, что более интересно, в нейрогенных нишах головного мозга в эмбриональном и постнатальном периодах [24][25][26]. В соответствии с его экспрессией, селективная активация CB2R стимулирует пролиферацию нейральных стволовых клеток в куль-туре и СВЗ у взрослых мышей [27][28][29][30].…”

“…In this sense, the endocannabinoid system could be a promising candidate, given its well-established protective role in different brain pathologies [15][16][17][18][19] and its reported capacity to modulate neural stem cell proliferation 20,21 as well as in vitro and ex vivo neuroblast migration 22 in physiological conditions. The most relevant cannabinoid receptors are cannabinoid type-1 receptor(CB1R), mainly expressed by neurons, 23 and cannabinoid type-2 receptor (CB2R), mostly located in microglia and, interestingly, in neurogenic niches of both embryonic and postnatal brain. [24][25][26] Consistent with its expression, selective activation of CB2R stimulates proliferation of neural stem/ progenitor cells in culture and in the SVZ of adult mice.…”