JWH133, a Cannabinoid receptor-2 agonist, attenuates neurological deficits and brain oedema after experimental Intracerebral Haemorrhage in mice
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Abstract: Intracerebral haemorrhage is a subtype of stroke which has highest mortality and morbidity rates and currently has no cure. Cannabinoid 2 (CB2) receptor expression is up-regulated in neuronal injuries. CB2 receptor agonists were found to be neuroprotective in brain injuries including ischaemic and haemorrhagic stroke. This study was carried out to investigate the effects of cannabinoid 2 receptor (CB2R) activation by JWH133 on intracerebral haemorrhage (ICH) induced blood brain barrier disruption and oedema formation. ICH was induced in experimental animals by collagenase injection which causes significant vascular disruption and concomitant increase in oedema; animals were then treated with JWH133. Sixty CD-1 mice were randomly divided into sham, vehicle, and JWH133-treated groups (1 mg/kg and 10 mg/kg). Neurobehaviour, brain water content, Evans Blue dye extravasation, haemoglobin content, lung water content, and body weights post ICH were assessed. JWH133 treatment attenuated neurological deficits at 24 and 72 hours post-ICH. The treatment also reduced brain water content and Evans blue dye extravasation but had no effect on haemoglobin content and lung water content. Administration of JWH133 treatment mitigated weight loss at 48 and 72 hours after ICH. The reduction in brain water content and Evans blue dye extravasation indicate that CB2 receptor activation decreases blood brain barrier disruption and brain oedema, resulting in improved neurological functioning. This suggests that activation of the CB2 receptor by JWH133 is neuroprotective after ICH and may be a therapeutic target. Further study is needed to explore the mechanisms by which these effects occur.
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