A Study Of The Effect Of Mild Hypothermia On Extending The Time Window Of Treatment With Restoration Of Blood Flow And On Its Protection Of Brain

Objective:The most effective treatment for acute ischemic stroke is the early re--storation of blood flow.(reperfusion therapy)to salvage the ischemic penumbrae,thefunc--tionally impaired yet still viable brain tissue,thereby improving clinical outco--me.,but many patient can not benefit from it due to the narrow treatmemt windowtime of 3 h--ours.Hypothermia has been suggested to be the only potent cerebrop--rotection appro--ach in clinic and also been proved to be the best cerebroprotectionapproach.thus,we study whether mild hypothermia (28-35℃)applied during rep--erfusion can prolong the time window ofrestorationofblood (reperfusion)andmechanisms of that and study it's neuroprotection mechanism.Methods:Methods:1.The adult rats were randomly divided into sham-operationgroup,MCAO24h,NT and HT respectively further divided into 6 subgroups(subjected ischemia for2,3,4,5and6h respectively and then all reperfused for 24h);2.the rats of hypothermia therapy is immediately loaded into ice-room.changingthe number of ice bags to keep natal temperatures by 31℃±10C.After 5hours,make them rewarm in the room Brain mild hypothermiawas achieved 5hoursimmediately after reperfusion period.The cerebral ischemia/reperfusion model of ratswere achieved by middle cerebral artery occlusion.3.The expressions ofAIF CytC HSP70and MMP-9 LN were detected byimmunohistochemistry.The infarct volumes were evaluated by TTC staining.Theneurological deficit score were measure by Longa.The water content of rats braintissue were measured by using dry-wet weight method.Result:The relationship between mild hypothermia applied during reperfusion withthe treatment time window of restoration of blood (reperfusion)and it's protectionduring ischemia/reperfusion.1.Compared with MCAO24h group in term of the infarction volume and score ofLonga:MCAO2-4h reperfusion groups of NT have significant difference (P＜0.01),MCAO5-6h groups reperfusion of NT have not significant difference (P＞0.05);MCAO2-5h reperfusion groups of HT have significant difference (P＜0.01),MCAO6h reperfusiongroups of NT have not significant difference (P＞0.05). 2.HT were lower significantly than NT in term of the infarction volume and score ofLonga and the water content of infarcted cerebra(MCAO2-5h reperfusion groups P＜0.01,MCAO6h reperfusion groups P＜0.05).The mechanisms of prolonging treatment time window of restoration of bloodflow.(reperfusion)by mild hypothermia applied during reperfusion and cerebralprotection of it.1.The study in the view of apoptosis1.1HT and NT were higher significantly than sham-operation in term of AIF Cyt CandHSP70 (P＜0.01).1.2HT were lower significantly than NT in term of AIF and Cyt C,HT were highersignificantly than NT in term of HSP70 (MCAO2-5h reperfusion groups P＜0.01,MCAO6h reperfusion groups P＜0.05).1.3Compared with MCAO24h group in term ofAIF CytC and HSP70:MCAO2-4hreperfusion groups of NT have significant difference (P＜0.01),MCAO5-6h groupsreperfusion of NT have not significant difference (P＞0.05);MCAO2-5h reperfusiongroups of HT have significant difference (P＜0.01),MCAO6h reperfusiongroupsof NT have not significant difference (P＞0.05).2.The study in the view of cerebral vasopermeability2.1There was negative relationship between MMP-9and LN r=-0.817,P＜0.01).2.2HT and NT were higher significantly than sham-operation in term of MMP-9 (P＜0.01).HT and NT were lower significantly than sham-operation in term of LN (P＜0.01)2.3HT were lower significantly than NT in term of MMP-9,HT were highersignificantly than NT in term ofLN (MCAO2-5h reperfusion groups P＜0.01,MCAO6h reperfusion groups P＜0.05).2.4Compared with MCAO24h group in term of MMP-9 and LN:MCAO2-4hreperfusion groups of NT have significant difference (P＜0.01),MCAO5-6h groupsreperfusion of NT have not significant difference (P＞0.05);MCAO2-5h reperfusiongroups of HT have significant difference (P＜0.01),MCAO6h reperfusiongroupsof NT have not significant difference (P＞0.05). Conclusion:1.The study demonstrated that the mild hypothermia applied duringreperfusion can prolong the treatment time window of restoration of blood flow.(reperfusion therapy).The reason for that is its potential capability of cerebral protection,via inhibiting capas-e-dependent and caspase-independent pathways of apoptosis andpromoting the expr--ession of Hsp70 protein.In one word,mild hypothermia canthoroughly inhibit apoptosis;inhibiting the expression of MMP-9 protein so allevia--ting the injury of micro--circulation,promoting endurance of microcirculation suffe--red ischemia/reperfusion.2.The study indicated that the mild hypothermia applied during reperfusion is thebest approach to extend the time window of restoration blood flow.(reperfusion).therapy,it can inhibit apoptosis in ischemic penumbra and alleviate the injury ofmicrocirculation and promote endurance of microcirculation suffered ischemia/reperfusion,thus in multiple way to interruput pathophysiology processing.It cansingnificently prolongthe time window.In conclusion,mild hypothermia is superior to other treatment approach aimed atprolonging time window,whoses mechanism were single,pertinence were poor (notdirectly to pathophysiology),effection were less power;In particular,it accuratelyreplicated the acute ischemic stroke in human being.since it is impossible thatpatients with stroke would be able to be treated with mild hypothermia before onsetof symptoms of stroke.,so that the mild hypothermia applied during reperfusion stagehave better clinical practicability.,the way of hypothermia was maturate,it's easy tobe popularized;because the mild hypothermia applied during reperfusion haveall-around cerebral protection,,it must have the good perspective that combine itwith the means of restoration of blood flow such as thrombolysis and/or brainprotection agents as well.