Neuroprotective Effect Of Polydopamine Nanoparticles On Cerebral Ischemia-Reperfusion Injury

Background:Stroke is the most threatening cerebrovascular disease to humans,as well as the second leading cause of death in the world.Early establish reperfusion cause oxidative damage,inflammatory response,and subsequently excitotoxicity cell death.Polydopamine nanoparticles(PDA)derived from self-polymerization of dopamine has man excellent free radical scavenging capacity,which attracted wide attention.This study aim to examine whether PDA can play its neuroprotective role in cerebral ischemia-reperfusion injury.Methods: Middle cerebral artery occlusion(MCAO)was adopted to establish a focal cerebral ischemia-reperfusion model in rats.Adult male SD rats(250-300 g)were randomly divided into four groups which consist of Sham+NS,Sham+PDA,MCAO+NS and MCAO+PDA.Rats in the PDA treatment groups received intraperitoneal injections of 5 mg/kg PDA,while rats in NS groups were given normal saline in the same volumes.Neurological function,size of brain infarction,brain water content and behavioral test were examined.Western blotting analysis and ELISA kits were used to check the expression of NF-κB signaling pathway,and inflammatory cytokines,including TNF-α,IL-1β,IL-10.Observe the activation degree of microglia by immunofluorescence.Evaluation of the biological safety of PDA in vitro and vivo experiments.Results: PDA proved its safety,has no obvious adverse effect on liver and kidney in low-middle concentration.Intraperitoneal administration of PDA alleviated neurological deficiencies,reduced size of cerebral infarction,brain oedema after MCAO induction(p<0.05).PDA decreased oxidative stress and inactivated phosphorylated NF-κB,furthermore decreased pro-inflammatory cytokines,TNF-α,IFN-γ and IL-1β,and increased anti-inflammatory cytokines IL-10(p<0.05),inhibited the over-activation of microglia.Conclusions: PDA relieved cerebral ischemia reperfusion injury,suppressed the inflammatory response,inhibited NF-κB signaling pathway activation by scavenge free radicals.These results suggest that PDA might have potential in treating brain inflammatory reaction and attenuating the cerebral ischemia-reperfusion injury.