Cannabidiol Can Provide Neuroprotection In A Mouse Model Of Intracerebral Hemorrhage And The Mechanism Research

Objective1 To study that cannabidiol treatment offered beneficial effects in many aspects of ICH-related brain damage, including overall neurological function.2 To study that cannabidiol is a potent anti-inflammatory and anti-apoptosis agent and may prove to be a potential target for research and development of drugs for clinical treatment of ICH and ICH related brain damages.Methods1 The animals were randomized to four groups: sham-operation group; control group; ICH+2 mg/kg CBD group; and ICH+20 mg/kg CBD group.2 The mice in ICH+20 mg/kg CBD group were treated with cannabidiol(20 mg/kg; was dissolved in a mixture of 2% of Tween 80 and sterile saline(0.8 mg/ml)) by intraperitoneal injection at 2, 12, 24, 48 h after operation, The mice in ICH+20mg/kg CBD group were treated with cannabidiol(2 mg/kg; was dissolved in a mixture of 2% of Tween 80 and sterile saline(0.8 mg/ml)) by intraperitoneal injection at the same time, and the mice in Sham-operation group and control group were administered with a mixture of 2% of Tween 80 and sterile saline(0.5 ml/20g) by intraperitoneal injection at the same time.3 In the first reference 1 h and 72 h cerebral hemorrhage after start of the experiment improved neurological function in mice(Grip Test) standards, praxiology score. 72 h mice in each group were sacrificed, cerebral edema, inflammation factor expression and apoptosis in each group were observed in mice brain samples.4 Through the above experiment, further design-related specific mechanisms of quercetin on nerve repair after brain hemorrhage experimental observation.Results1 Neurological score In the first 1 h and 72 h administered the mice were observed neurological deficit scores, compared with cerebral hemorrhage, ICH+CBD 20mg/kg group of neurological symptoms in mice were significantly improved neurological function value significantly lower, the difference was statistically significant(P<0.05).2 Brain water content 72 h afterr operation, comparing with the Control group, ICH+CBD 20mg/kg group can significantly reduce brain water content, the difference was statistically significant(P <0.05).3 Inflammation Compared with Contol group, ICH +CBD 20mg/kg group were able to significantly reduce the expression of inflammatory factors, the difference was statistically significant(P<0.05); Western Blot results showed protein HMGB1 expression was significantly lower, the difference was statistically significant(P<0.05); immunofluorescence staining showed that microglia cells was significantly reduced, and the difference was statistically significant(P <0.05).4 Cell apoptosis Compared with Contol group, ICH +CBD 20mg/kg group were able to reduce the protein NICD and PARP-1 protein expression was significantly lower, the difference was statistically significant(P<0.05); Tunel staining method showed significantly reduced the number of apoptotic cells, the difference was statistically significant(P<0.05); immunofluorescence staining showed that caspase-3 positive cells was significantly reduced, and the difference was statistically significant(P <0.05).ConclusionsOur study showed that cannabidiol treatment provided beneficial effects in many aspects of ICH-related brain damage, including overall neurological function. Cannabidiol is a potent anti-inflammatory via a mechanism of inhibition the expression of protein of HMGB1 and the generation and activation of microglia. Cannabidiol is also a potent anti-apoptosis via the inhibition of Notch path way and then inhibited the activation of the protein of PARP-1 and caspase-3, at the end, can inhibit the cell apoptosis.