Acute Effects of Cannabis sativa on Ischaemia/Reperfusion Injury in the Rat Brain
DOI:
https://doi.org/10.12974/2309-6179.2017.05.06Keywords:
Cannabis, brain ischemia and reperfusion, oxidative stress, neuroinflammation.Abstract
We investigated the effect of Cannabis sativa extract on brain damage, oxidative stress and inflammation in rats with transient global cerebral ischaemia. Rats were subjected to bilateral common carotid artery (CCA) occlusion for 45 minutes followed by 4 h of reperfusion. Rats were treated with cannabis at a dose of 20 mg/kg (expressed as Δ9-THC) intraperitoneally (i.p) either before CCA, at time of reperfusion or after reperfusion. Alternatively, cannabis was given i.p. daily for 2 days before surgery. Markers of oxidative stress (malondialdehyde, reduced glutathione, nitric oxide) and the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α) were determined in brain tissue. Histopathological evaluation was also done. Compared with the sham-treatment group, CCA occlusion resulted in increased brain malondialdehyde (54.5 ± 2.0 vs. 26.0 ± 1.45 nmol/g. tissue; p<0.05) and nitric oxide (75.2 ± 3.2 vs. 31.3 ± 3.0 mmol/g. tissue; p<0.05) contents along with decreased brain reduced glutathione (6.6 ± 0.14 vs. 8.28 ± 0.31mmol/g. tissue; p<0.05). There was also a pronounced rise in brain TNF-α concentrations (2248 ± 105 vs. 51.42 ± 3.21 pg/g. tissue; p<0.05). Cannabis sativa significantly increased reduced glutathione (by 30.3%-60.6%; p<0.05) and alleviated the increase in nitric oxide levels (by 51.5%- 58.5%; p<0.05) in the ischaemic brain tissue. Cannabis given before or at time of CCA occlusion significantly reduced brain TNF-α by 24.4% and 26.7%, respectively (1699 ± 80 and 1647 ± 54 vs. 2248 ± 105 pg/g. tissue; p<0.05). Histopathological examination of the cerebral cortex from rats subjected to CCA occlusion revealed gliosis, vacuolation and widespread neuronal degeneration. Cannabis given as a single dose 1h prior to CCA ligation or as 2 days pretreatment conferred protection against the ischaemic neuronal injury. It is concluded that in cerebral ischaemia the prior administration of cannabis exerted neuroprotective effects which could be accounted for by a decrease in nitric oxide and in the inflammatory response.
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