| Background and objectiveMany fatal cases of traumatic subarachnoid haemorrhage(TSAH), were caused by slightbeating on face or/and necks after excessive drinking. Review the articles reported, thephysiologic and toxicological effects of drinking to evoke the TSAH were miscellaneous:Dinking could cause cerebral vessels expand,it was more sensitive to the external force andeasier to rupture and hemorrhage. Dinking could inhibit blood coagulation and vasoconstriction.Drinking could cause ataxia and influence the response of CNS, make musculi colli relax; reducethe capability of dodging or resisting violence, in this case,neck was easy to be overrotated andhyperexpanded, the Intracal blood vessel such as vertebral artery and basilar artery were easy tobe damaged,and also, the drinker was at a much easier irritable mental status than normal.All ofthese were considered as important factors to evoke TSAH. We established TSAH model infuddled mice, observe the expression of Ngb and Hif-1α, the activity of Na~+K~+-ATPase wasdetected in the brain tissue. The effect of drinking upon neurons oxygen supply, energymetabolism and sodium pump function were discussed, in order to primarily explore the effectsof morphous,metabolism and function of neurons after excessive drinking, and the possiblemechanisms or relationship between excessive drinking and the happening of fatal TSAH.Materials and MethodsMale SD mice, 250～350g, were grouped into acute fuddled team and chronic fuddled team.Using pure water instead of alcohol in the control group. The edible alcohol of Erguotou ofPeking(52％v/v)was injected into mice's stomach through esophagus. The acute team wasinjected alcohol by 15ml/kg for one time; the chronic team is injected by 2 times per day at 8hours' intervals, 8ml/kg each time in the first 2 weeks and 12ml/kg each time in the next 2 weeksfor one month in total. Used same amount of pure water in the control group. Self-made iron ofsimple pendulum duplicate apparatus of brain injury was used to duplicate the mice's model ofclosed cerebral trauma which has the phenomenon of go-by obstruction of brain's function twohours later after the injection in acute team and the last injection in the chronic team. The bloodacquired by cutting the mice's head after 0.5thh, 2thh, 4thh, 6thh, 12thh in acute team and at 2thh in chronic team, with each team including 7 mice in acute fuddled and 17 mice in chronic fuddledand 5 mice in injected water. The changes of mice's vital sigh and the concentration of theethanol in the blood were observed, the changes of histomorphology and the expression of Ngband Hif-1αwere observed by HE and immunohistochemistry, detect the activity of Na~+,K~+-ATPase in the brain tissue, and the data tested with SPSS 13.0 statistic software and Excel. Results1. Animal's behavior and the BAC changesThe acute group's concentration of ethanol was (134.7±4.5)rag/dl at 0.5thh, then reach thehigh-peek of (188.8±5.8)mg/al at the 2thh after injected, and then step down gradually to(1.7±0.5)mg/al at the 12th hour.The mice appeared excitable a short time after drinking: moving continuously andunstably. About 0.5h later, they appeared some clinical manifestation of acute alcoholism such aslying on the side, hypnody, body-righting reflex disappearing, the respiration and the bloodpressure lowering. After be replenished alcohol, the mice of dead group appeared weak and limp,reponse reduced hugely, respiratory rhythem negatived, intermittence deep-large respiratory,about 4 hours later, the respirator taper to disappear,then heartbeat arrested.In the chronic group,the hair becomes rough and dim, the spirit becomes frustrated,mice were weightless anddecreased food-intake.2. Incidence rate and death rate of TSAH and SAHThe incidence rate and death rate of TSAH are28.6％and 0 in acute group, but 82.4％and58.8％in chronic group, The incidence rate of spontaneous SAH are 0 in acute group and 5.9％in chronic group, death rate are both 0.3. HistomorphologyThe acute group's brain showed slight congestion and swelling to different extent in eachsection of time. In histology of TSAH mice, lamellar and punctiform SAH can be seen. Theneuron and the microlia was slightly injured, which was mainly slightly hydropicdegeneration.In dead group, the neurons were swelling from middle to severe.One month afterthe last drinking in chronic group, the mice's brain showed congestion and swelling to differentextent, and SAH to different extent. In histology, the arachnoids were rarities, congestion andswelling, and SAH can be seen. The neuron and the microlia was highly and widespreadhydropic degeneration, and sporadic neuron necrosis was accompanied; the amount of neuron was reduced obviously(p＜0.01), microglia widely hyperplasy.4. The expression changes of Ngb,Hif-1αThe expression of Ngb in brain tissue's neuron of normal mice was conspicuous, and a littleneuron express feeble Hif-1α. There was no difference of the positive cells of Ngb between theacute group and the control, in acute fuddled group and fuddled with beating group, the integraloptical density (IOD) of Ngb in the pallium, hippocampus, cerebellum, and brainstem was higherthan the control group(P＜0.05, P＜0.01), the positive cells and IOD of Hif-1αwere higher thanthose in the control group(P＜0.01), the positive cells and IOD of Hif-1αof acute group werelower than those in fuddled with beating group(P＜0.01). In chronic group, the positive cells ofNgb were lower than those in the control group (P＜0.01),but,there was no difference incerebellum, the IOD of Ngb was higher than the control groups (P＜0.05), both of the positivecells and IOD of Hif-1αwere stronger than control group(P＜0.01).5. Detecting the activity of Na~+, K~+-ATPaseThe activity of Na~+,K~+-ATPase of normal mice pallium, hippocampus, cerebellum, andbrainstem was much higher, and in the acute fuddled group was begin to descend from 0.5thh,faster between 2th～4thh(P～0.01),it began to recover after 6thh, recoverd normal after 12thh. Inacute fuddled dead group,it descened very obviously(P＜0.001).In chronic group, the activity ofNa~+,K~+-ATPase was lower than the control group,but higher than the acute group(P＜0.05).Conclusions1. The stable model of TSAH on the fuddled mice was successfully established, and provedthat there were closely correlations between slight violent beating after fuddled and the higherincidence rate and death rate of TSAH. It illuminated that the drinking should be set intoconsideration sufficiently while analyzing these cases of TSAH after drinking in forensicmedicine. The slight external force should be a mortal wound in perchance condition; insobrietyand its physiologic and toxicological effects should be an assistant cause of death.2. Alcohol and its metabolic product could influence the funcition of Ngb, it obstructed theoxygen supply and energy metabolism; caused hypoxia, and the sodium pump malfunction. Thismaybe play the roles on ataxia and the anomalous CNS excitability after drinking.The hypoxiastatus was slighter in chronic fuddled group, it might be the Hif-1αinduce function that couldimprove oxygen supply, and also, the activity of Na~+, K~+-ATPase was compensated enhanced.Longtime hypoxia status after chronic alcohol intragastric administration obstructed the oxygensupply and energy metabolism, the sodium pump malfunction.These disturbances may aggravatethe neuron cell injury, it accorded with not only human encephalatrophy of long-term alcohol but its vulnerability bad prognosis.3. The experiment confirms that the brain tissue is in a hypoxia status after acute andlongtime alcohol intragastric administration. Particularly, the activity of Na~+, K~+-ATPase in acutefuddled dead mice's brain tissue was cut down conspicuously, it illuminated that, the obstructionof oxygen supply and energy metabolism of brain neuron , the sodium pump's seriousmalfunction, the neurons energy exhaustion probably are one of mechanisms of alcoholism deaths. |
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