CO-induced Brain Damage And The Role Of The TRPM2 Channel

BackgroundCarbon monoxide(CO)poisoning is the most common cause of death from poisoning in the world.It can cause neuropathological changes such as acute brain injury and delayed encephalopathy.Some studies have shown that CO poisoning is mediated by oxidative stress and glial cell activation,thus damaging neurogenesis and causing neuronal necrosis or apoptosis leading to cognitive dysfunction.Transient receptor potential melastin-related 2(TRPM2)channel,as a potential ubiquitous molecular mechanism mediating oxidative damage,is highly expressed in glia.TRPM2 channel plays an important role in regulating the activation of glia cells and production of proinflammatory mediators as well as oxidative stress-mediated neuroinflammatory response.Finally,TRPM2 knockout mice were used to investigate the role of TRPM2 in mediating CO-induced neuronal and cognitive dysfunction.Based on these new findings,the prospect of the TRPM2 channel as a new therapeutic target for CO-induced was discussed.ObjectiveCarbon monoxide poisoning can cause long-term neurological and emotional complications,including impaired learning and memory.However,the mechanisms underlying such pathological outcomes are not fully understood.There some evidence to suggest a role of oxidative stress in CO-induced brain injury and alteration in glial cell function.The purpose of this study is to investigate whether TRPM2,an oxidative stressactivated channel,is involved in CO-induced brain damage and alterrations in cell function in mice through the intervention of TRPM2 channel after carbon monoxide poisoning,so in order to identify a new target for the treatment of CO poisoning.Methods1.Wild-type C57 mice were used to establish a CO poisoning model via intraperitoneal injection of CO.Blood samples were collected to measure Hb CO % to confirm the poisoning degree.Behavioral experiments were conducted to observe the learning and memory ability of infected mice.2.The effects of CO on neurons,astrocytes and microglia were examined.3.TRPM2-KO mice were treated with CO,and the changes in neurons and glia cells,and ehaviors were examined.As described above for wild-type mice.Results1.During the establishment of CO poisoning mouse model,the Hb CO level in venous blood increased sharply with the increase in injection CO dose.The survival rate of mice after CO poisoning was doss-dependent.2.CO poisoning induce impairment in learning and memory and anxiety in wildtype mice,with the effects becoming more severe with the increase in CO dose.3.CO poisoning increased the number of GFAP-positive astrocytes in hippocampal CA1 region of mice poisoned with the increase reaching significant level with the dose of130 m L/kg.4.Compared with wild-type mice exposed to the same dose of CO,the activation of microglia cells and the damage of neuronal cells in TRPM2-konchout mice were alleviated.ConclusionCO poisoning induced brain injury and alteration in glial cells in mice.TRPM2 plays an important role in CO-induced brain injury and alteration in cell function,providing evidence to suggest TRPM2 channel as a new target for the treatment of CO poisoning.However,the molecular mechanisms by which TRPM2 plays such a role in CO induced brain injury remains to be further studied.