Experimental Study On Intracarotid Therapy Of Acute Cerebral Infarction Out Of Time Window

Research purpose and backgroundThe prevalence of stroke increaseswith the ageing process of the human society. Thereare about2.5million new cases each year in China, most of them are ischemic stroke[1].Their high fatality rate and disability rate significantly raise the health care expenditure byState, the family and personal. It has been a tackling key problems faced by the world totreat cerebral infarction.The current preferred super early acute cerebral infarctiontreatment is arterio-venous Thrombolysis, in which more therapeutic time window isrequired, like as3-4.5hours for thrombolytic and6hours for intra-arterial thrombolytictherapy. One of the reasons why thrombolytic time window limits exists is that the harmcaused by reperfusion after the time window outweigh farly the treatment benefits ofrevascularization.Often the patients sent to the hospital have lost the opportunities ofthrombolytic, thus it has attract the general medical care and researchers to find effectivetreatment means beyond the time window.Conventional vein treatment method is simple, while the drug is often systemic scopedelivery, which always reduce greatly the drug concentrations actioned at the targetcells.Luckily, accurate local delivery of drug has been achieved through current matureVascular Interventional means, such as in the application of embolization andchemotherapy for tumor, also like the arterial Thrombolysis and dissolution of cerebralVasospasm in the field of Neurology. There is few application in intracranial arteriestopical medication apart from intracranial tumor.What attract us is whether it is feasible to save the penumbra (IschemicPenumbra,IP)and interventinfarction through altering the internal carotid drug delivery via artery beyondthe time window. Generally speaking, IP could last for about24hours[2], during then thepatients are often able to reach the hospital and get the relatively timely treatment. The carotid artery Vascular Interventional local delivery could let the drug reach the brainrapidly, and maximize the effective local treatment concentration. Theoreticallyspeaking,the favorable conditions on both time and spacehave already provide the necessityfor further investigation.Edaravone, as a free radical scavenger and a neuroprotective agent has been widelyrecognized to be able to save the IP chain and reduce the chain reaction in reperfusion ofinjured free radicals, as well as relievethe brain edema and celldamage.It has been includedin China’s guidelines for management of cerebral infarction in acute stage of strokemedication. It is reasonable to choose it as our experimental therapeutic consideringitsdefinite medication effect, which need no more argument. Moreover,it has an importantrole in increasing final survival rate of tested dogs for further observation.This experimental work will adopt the middle cerebral artery thrombosis model indogs and compare the locally arterial treatment beyond time window to a regular veintreatment. We’ll observethe intervention characteristics of the two sets of therapy for acutecerebral infarction by using brain imaging and neurologic score evaluation instruments,which would provide a solid basis for future clinical treatment.Materials and methodsTwenty Healthy Chinese rural dog are randomly divided into arterial treatment groupand vein group for comparison.Firstly, each group was made into the Middle cerebral arteryocclusion (MCAO)in digital subtraction angiography (DSA).Then, MagneticResonanceImaging(MRI) was scanned3hours,6hours and30hours after operationand the apparentdiffusion coefficient (ADC) andrelatively apparent diffusion coefficients (rADC)aremeasured in3interested zones ofthe ischemic lesions and the corresponding healthyregions in experimental.The edaravone was injected through the5F single bend ductinjection for the group of6h point scan indwelling arterial, in comparison conventionalintravenous infusion for edaravone injection for the group of veins.After then, observationand neurological function scoring for2nd day,3rd day and1week after operation areconducted. Some dogs are put to death in1week for pathologic examination.ResultsThe average of ADC for all groups at various instants are reduced in comparison tothatof the contralateral regions, which is of statistical meaning (P<0.05). The minimum magnitude arise in Stroke center (1#mark), medium magnitude in the edge region (3#mark)and maximum magnitude in the IP region (5#mark) at every same instant.For each markpoint, the maximum magnitude arise at3h, mediummagnitude at6h and minimummagnitude at30h.There were no statistically significant differences in the rADC values (P>0.05) ofthetreatment group at3h or6h in comparison to that of the control group.This is also the casefor the average ADC, rADC of the infarction treated with central location (1#mark), thetreatment of fringe groups (3#marks). While, the ADC(519.68±57.03×10-6mm2/s) andrADC (63.65±5.93%) values at30h of the treatment group IP range (5#marks) arestatistically higher than that of the control group, in which ADC is454.58±71.44×10-6mm2/sand rADC57.24±7.4%,respectively.The pathology check shows that the infarction area, which is white, differentiateclearly from the normal tissue. And we can see large sieve-like softening lesions, inwhichthe dead vacuole-like cells only have solid contracted nucleus without cell structureand are sporadic within the invasion of lymphocytes. Moreover, in the infarct centers,thesmall blood vessels dilate, blood vessel wall thicken, endothelial disorders, a large numberof red blood cells appear and red exudate blood obviously seep throughthe vessels.The nerve function score of treatment group on the2nd day,3rd day,7th day were6.4±0.84、5.1±1.20、4.3±1.06，and6.9±0.74±0.82,5.3,6.0±0.95for the comparedgroup.There are no statistically significant differences (P>0.05) in the dogs neurologicalfunctional scores2nd day,3rd day after operation among the various groups groups. Butsuch difference arise in1week (P<0.05), for which the scores of the treatment group arelower than that of the control group.Conclusion:1. The ADC values around the ischemic lesions decreased significantly in comparisonto that of the conterpart region, which is of the with the characteristics stteping up from thecenter to the outward, and the ADC values fall even more evidently over time.2. The ADC, rADC values in the IP regions of the variously treated group6hour afteroperation decline relatively more slowly in comparison to the control group, which showthat protection over the treatment group IP is better than the control group.3. The neurological functional scores for the two groups of dogs are not significantly different2nd day and3rd day after operation. The neural function scores of treatment studygroup is lower than that of the control group in1week after operation, while of betteroverall recovery than the control group.4. Intracarotid therapy is an effective means of improving the prognosis of acutecerebral infarction that over time window.