Allicin Attenuates Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

BACKGROUD:An Subarachnoid hemorrhage(SAH)is caused mostly by the rupture of aneurysms on cerebral arteries leading blood into the subarachnoid space.It has 35%mortality rate though it accounts for only 5%of all strokes.Survivals often face with neurological and cognitive functional impairment.A tremendous amount of studies show that early brain injury(EBI),which refers to the acute injuries to the whole brain in phase of the first 72 hours following SAH,instead of cerebral vasospasm(CVS),plays a more significant role in the disastrous outcome for patients with SAH.The pathogenesis of EBI included elevation of intracranial pressure(TCP),reduction of cerebral blood flow(CBP),and global cerebral ischemia,which initiated secondary injuries such as inflammation and oxidative stress that all ultimately lead to neuronal cell death,BBB disruption,and brain edema formation.Garlic,which has a long story to be used for treating various diseases in traditional Chinese medicine,is widely used as a seasoning or condiment for its pungent flavor around the world.When crushing the garlic clovesand,Allicin(diallyl thiosulfinate),which is the most biologically active compounds and responsible for the typical smell and most functions in garlic,is produced.Allicin has been shown to exert a wide variety of biological properties,including antioxidant and anti-inflammatory effects,the protection of cardio-vascular system,the inhibition of platelet aggregation,and antibacterial activity.Researches about antioxidant effect of allicin showed that allicin is effective antioxidants against the oxidative damage caused by nicotine.Allicin has been reported to exert neuroprotection against spinal cord ischemia-reperfusion injury in rabbits,to protect against traumatic brain injury in rats,to protect rat cortical neurons against mechanical trauma injury,to attenuate ischemic brain injury,to protect spinal cord neurons from glutamate-induced oxidative stress.In the present study,the effect of Allicin on early brain injury after experimental subarachnoid hemorrhage in rats was investigated.Methods:250g-300g adult male Sprague-Dawley rats were used for experiments.Rats were assigned randomly to the following groups:sham-injured groups(n =15);SAH groups(n =15);SAH + vehicle groups(n =15);SAH + 30 mg/kg Allicin groups(n =15);SAH + 70 mg/kg Allicin groups(n =15).The prechiasmatic cistern rat SAH models which produced according to previous report were used in this study.The Allicin was dissolved in 10%dimethylsulfoxide(vol/vol,in 0.9%saline).Two doses of Allicin(low:30 mg/kg;high:70 mg/kg),which was administered by intraperitoneal injection at 30 minutes after SAH,were used to test its different neuroprotective effects.An equal volume of 10%dimethylsulfoxide was administered in sham-injured groups and SAH + vehicle groups.Assessments including neurological deficit,body weight loss,brain water content,Evans blue(EB)extravasation,Western blot,histopathological study,and biochemical estimation were performed at 24 hours after surgery.Results:Of 75 rats used in our experiment,9 died after the operation.The mortality rate at 24 hours after surgery was 0%(0 of 15)in the sham-injured group;15.4%(2 of 13)in the SAH group;23.1%(3 of 13)in the SAH + vehicle group;16.7%(2 of 12)in the SAH + 30 mg/kg Allicin group;15.4%(2 of 13)in the SAH +70 mg/kg Allicin group.With therapy(70 mg/kg Allicin,rather than 30 mg/kg)30 minuters post SAH,groups showed better neurological scores at 24 hours.Significant differences could be founded in body weight ratio comparing the SAH + vehicle groups with SAH + Allicin groups.Treatment with 70 mg/kg,not 30 mg/kg,Allicin significantly reduced brain edema and EB extravasation at 24 hours after SAH.Assessments at 24 hours after SAH showed that treatment with 70 mg/kg Allicin at 30 minutes after SAH significantly restrained the expression of cleaved caspase-3,mitigated the severity of neuronal degeneration,decreased the proportion of apoptotic neurons and the elevated MDA levels,and increased the suppressed GSH and SOD levels.Conclusion:We demonstrated for the first time that Allicin extenuated brain edema and blood-brain barrier dysfunction,improved neurological outcomes by the suppression of apoptosis and oxidative stress damage after SAH in experimental models,which may shade new light on the treatments of SAH.