Protective Effect Of Sulforaphane On Nerve Injury Induced By Chronic Cerebral Ischemia

ObjectSulforaphane is a natural componese in cruciferous plants such as broccoli,brassica capitate and carrots.And it is considered to be an effective factor which could enhance Nrf2 and heme oxygenase 1(HO-1)expression in human.Heme Oxygenase 1(HO-1)is an important enzyme in the process of heme metabolism,which could convert heme to biliverdin.Some studies found that HO-1 on ischemic brain damage which caused by oxidative damage,have important optimistic roles.Sulforaphane was used to active the Nrf2 pathway and upregulate the synthesis of HO-1 in vivo and the protection of chronic cerebral ischemia and its mechanism were studied.MethodsBilateral common carotid arteries were ligated to build the chronic cerbral modal.White matter damage and Aβ deposition were observed in different stages.The optimal effection of sulforaphane on white matter damage and Aβ deposition were determined after chronic cerebral ischemia.In brife,the expression of MBP,SMI32 and NF200 in white matter,showed the optimal relationship between the protection of sulforaphane of white matter damage and Nrf2 / HO-1.Results1.After 2-VO surgery,rats were in a chronic cerebral hypoperfusion state gradually which caused by cognitive dysfunction.6 weeks later,the rat’s cognitive function decreased significantly.The rats cognitive function could be protected by using Sulforaphane.2.Changes of Nrf2 and HO-1 in brain tissueIn chronic brain hypoperfusion rats model,the expression of Nrf2 and HO-1 were increased,and sulforaphane significantly up-regulated the expression of Nrf2 and HO-1 in brain tissue.In the early stage of cerebral ischemia(3d and 1w),sulforaphane induced Nrf2 nucleus transcription of the cerebral cortex,and up-regulated the expression of HO-1.3.The protection of neurons6 weeks after the chronic cerebral hypoperfusion,neurons in hippocampal CA1 region were stained with neun immunofluorescence.The number of positive cells was decreased in vehicle group compared with SF group.The neurons of rats were divided into two groups: the neurons in the cerebral cortex of the rats were significantly reduced,the number of neurons was decreased and the nucleus was necrotic.Sulforaphane protects neurons in SF group,and the damage is significantly less than the other group.4.Protection of sulforaphane on white matterThe corpus callosum(CC)and striatum(Str)of white matter damage were caused by chronic brain perfusion.White matter fiber disorder,sparse,visible vacuolar changes,some new vesicles were observed.The radish sulfur could reduce the chronic cerebral hypoperfusion.5.Aβ deposition6 weeks after surgery,Aβ deposition were observed in the cortical(CTX)and hippocampus(HIP)in veh group,and Aβ deposition was significantly reduced by the treatment of sulforaphane.Western blots showed that the expression of Akt / Gsk-3β pathway was inhibited by sulforaphane at 1w,3w and 6w after operation,and the deposition of Aβ was reduced by inhibiting Akt / Gsk-3β pathway.Conclusions1.2-VO chronic cerebral ischemia model is stable and reliable.Chronic cerebral ischemia can cause brain long-term chronic damage,and then the white matter damage,neuronal apoptosis in the hippocampus and cortex,Aβ protein deposition.All can lead to decrease of cognitive function.2.Sulforaphane could slow down the cognitive impairment by chronic cerebral ischemia.3.Sulforaphane could reduce white matter damage,protect neurons from ischemia-induced oxidative stress injury,reduce brain tissue Aβ deposition through the up-regulation of Nrf2 / HO-1 expression in the brain.