| BackgroundMoyamoya disease,also known as Skull base abnormal vascular network disease,is a kind of cerebrovascular disease characterized by progressive stenosis or occlusion at the terminal portions of the bilateral internal carotid arteries with arterial collateral vessels at the base of the brain.The initial diagnosis of Moyamoya disease is mainly based on Suzukis' diagnostic criteria in 1969.According to the development process of Moyamoya disease,Suzuki and Takaku came up with the idea that this disease can be divided into 6 periods by angiography.Relatively,Moyamoya disease is a new disease.Its etiology,natural clinical course and the treatments are not clear,and all of these are on the research stage.Its clinical manifestations are diverse,such as to cerebral hemorrhage,cerebral ischemia,epilepsy,headache and mental decline.The clinical manifestations between children and adult patients are not the same.Children is mainly characterized by ischemic symptoms,while adults are characterized by symptoms of cerebral hemorrhage and part of the cerebral ischemia symptoms.At present,the treatment of Moyamoya disease is divided medical treatment and surgical therapy.Medical treatmentMoyamoya disease should only temporarily treated by conservative medical treatment,when the Cerebral perfusion reserve is in the normal range,otherwise active extra-and intra-cranial surgical cerebral revascularization can lead to increased intracranial pressure by making the brain tissue over perfusion,even the emergence of normal perfusion pressure breakthrough syndrome;when the Cerebral perfusion reserve has been reduced,Moyamoya disease should be treated by surgical therapy as soon as possible.Currently,the main drugs include antiplatelet agents,vasodilator,antifibrinolytics and fibrinolytic agents;other drugs including anticonvulsant drugs and steroids given to patients who are epileptic and intracranial hypertension respectively.Antiplatelet agents prevent the cerebral infarction mainly through avoiding the formation of thrombus in artery stenosis.For calcium antagonists can decrease the frequency and severity of the repeated Transient Ischemic Attack,it has a good effect on Moyamoya disease patients with Obstinate Headache or Cephalagra.While calcium antagonists can lead to blood pressure drops,it should be used prudently.To sum up,the effect of medical treatments are uncertain.At present,more and more scholars believe that surgical cerebral revascularization is the most effective treatment to improve hemodynamics and reduce the risk of secondary stroke.When the above treatments are not effective,TIA could not be recovered or permanent cerebral infarction will appear directly.It is known to all that cerebral infarction is a challenging problem.In this case,few drugs are effective to treat cerebral infarction.In recent years,great progresses have been made on the pathogenesis of cerebral ischemic injury.There are many theories studying the pathogenesis and the development of this disease.Among these theories,excitatory amino acid(EAA)theory,based on ischemic cerebral neuron damage,has been widely noticed:The application of brain microdialysis find that the level of EAA show significantly increased in extracellular fluid of the ischemic area during cerebral ischemia.When the large amounts of glutamate is accumulated in extracellular fluid,the ionotropic EAA receptor can be activated,Ca2+ and Na+ channels will be opened and the ion permeability will be changed.In this way,the above changes lead to nerve intracellular and extracellular ionic equilibrium disturbance,and lots of intracellular Ca2+ and Na+ result in swelling and death of nerve cells.Tremelliform glutamate transporter in astrocyte plays a significant role in cleaning extracellular glutamate and preventing non-controlled neuronal discharge caused by glutamate overload in synaptic cleft.We find that inhibiting EEA release can reduce the area of cerebral infarction in the early animal experiments,while the existing EAA-antagonists have great adverse effect or have no significant effect in clinical trials.Nowadays,there is a research focus in neurography:Resveratrol(Res)can protect Nervi cerebrales and preparatory testing result has proved that Res can also decrease cerebral ischemia and cerebral ischemia-reperfusion injury.There has been a lot of debates among the protective mechanism.Therefore,it is necessary for us to find out some methods with lower side effect and satisfactory effects to inhibit EAA excitotoxicity.It is neurologists' dream to find out some effective neuroprotective drugs,so it is important for us to study Res's effect and mechanism in treating neurological diseases.Surgical therapyThe study on Cerebral Blood Flow(CBF)based on O-gawa's 133Xe intravenous injection shows that CBF in hemisphere will both decreases as patients with moyamoya disease and normal people get older,but the decrease in patients with moyamoya disease is more significant;for normal people,regional cerebral blood flow(rCBF)plays a dominant role in frontal lobe,while for patients with moyamoya disease,in occipital lobe,which means that the ischemia in Internal Carotid Artery(ICA)is more significant.CBF in hemisphere is associated with occlusive degree showed by angiography in adolescent patients with moyamoya disease.As the occlusive degree getting severer,CBF in hemisphere is decreasing,and rCBF is also increasing in occipital lobe.Theoretically,all the surgical methods that can increase CBF in the cortex directly(especially the front CBF)can be adopted and that is what the direct anastomosis bypass operation theory base on.Under natural conditions,the formation of collateral circulation between extracranial vascular and cortical vessels is restricted.Indirect bypass operation has been used to treat Moyamoya disease,and has made a real progress in recent years.In addition,the formation of the collateral vessels after indirect bypass operation can also reduce the formation of microaneurysm caused by Intracalvarium idiopathic collateral vessels overexpansion and intracranial hemorrhage caused by angiorrhexis.At present,there are two main surgical therapies:one is direct bypass,which refers superficial temporal artery to middle cerebral artery anastomosis(STA-MCA);the other is Encephalo-duro-arterio-synangiosis,(EDAS).There are two advantages in the direct anastomosis bypass operation:(1)works rapidly.This operation can reduce CBF obviously and improve blood flow to the ischemic area.During operation,infrared imaging system is used to monitor and we can obviously find that both hemodynamics and temperature distribution of cerebral cortex are changed.(2)The load of Moyamoya disease vascular is reduced.Therefore,the risk of brain hemorrhage is decreased.There are five disadvantages in the direct anastomosis bypass operation:(1)To patients with Moyamoya disease,arteriae cerebri media and other blood vessels are small and even fragile.Therefore,vascular anastomosis is difficult and demands excellent surgical technic.(2)Middle cerebral artery will be temporally blocked,and it may aggravate cerebral ischemia.(3)May damage the collateral vessels which has been formed.(4)The anastomosis sites may be constrictive or occlusive,therefore,its long-term-result is uncertain.(5)Partial hypertransfusion after operation may temporally aggravate neurologic function,even induce vasogenic edema in the anastomosis sites which will cause Delayed Intracerebral Hematoma.Though EDAS takes effect more slowly(nearly 3 mounths),it is simple and does not block arteriae cerebri media.Generally speaking,this method will not damage the collateral vessels which has been formed,rarely aggravate neurologic function and cause vasogenic edema and Delayed Intracerebral Hematoma.As a result,the therapeutic effect of two methods still provoke controversy.Part ? Analysis of the effective that moyamoya disease treated by improved Encephalo-duro-arterio-synangiosis-a study of the surgical therapy associated with moyamoya diseaseObjectiveIn this study,the comparing of differences from clinical symptom,iconography and brain functions before and after operation were made to evaluate the effective to the moyamoya patients treated by the improved EDAS.Method1.PatientsWe Collected 36 cases of the moyamoya disease clinic data treated by improved EDAS in our hospital from January 2011 to March 2013,among these patients,22 cases are male and 14 cases are female,age from 4.0-51.2.They were divided into two groups:in group ? there are 29 ischemic Moyamoya patients;in group ? there are 7 hemorrhagic patients.Among all the patients,5 patients were treated by hibateral surgical operation,and 31 patients were treated by improved EDAS.2.Examines contentAll the patients were tested by Digital Subtraction Angiography(DSA)and single photon emission computed tomography(SPECT)before operation.Magnetic Resonance(MR)and Magnetic Resonance Angiography(MRA)depend on patients'conditions.All the patients should be tested by SPECT after operation of 3-4 mouths.DSA or MRA was tested by patients'willingness.3.Surgical methodUsing improved EDAS.During operation,we separate the ramus parietalis arteriae temporalis superficialis or ramus frontalis arteriae temporalis superficialis for most patients,and we separate arteriae occipitalis for some patients.Skin incision walks alone the arteries.Both sides of arteriae temporalis superficialis will leave 3.0-5.0mm anadesma,and the isolated length is about 9.0-10.0cm.Separateing the arachnoid widely under a microscope,we put arteriae temporalis superficialis upon pia mater.Sewing up the endocranium partially,we will put it upon arteriae temporalis superficialis,and then fixed bone flap.If the patient has Moyamoya disease in both sides,he should have another operation to the other side after 3 mouth.4.The difference of clinical symptom before and after operationSymptoms before operation:muscle weakness?sensory disorder?language disorder?unrelenting headache?visual impairment,etc..We will compare the difference before and after operation.5.The difference of imaging before and after operationRe-checking DSA or MRA 3 months after operation.We will check the situation of Intracranial and extracranial vascular in operational area and whether the Moyamoya vascular will decrease in basis cranii.6.The difference of SPECT before and after operationSPECT will refer partial brain functions to some extent because rCBF is parallel to partial brain functions.As a result,we will check SPECT 3 mouth after operation to know the changes of the cerebral perfusion.Comparing the average counts of SPECT in operative regions,we are willing to know the changes before and after operation.Result1.Clinical symptoms36 patients were treated by improved EDAS.We find that all the patients'situations are getting better or the disease has not got worse or emerged new symptom.Meanwhile,all the patients have no correlative complications.2.Imaging resultsAll the patients were checked by imaging after operation.There are 41 Moyamoya hemispheres were treated by improved EDAS,65.9%(27/41)patients were getting better.There are 34 cases with Ischemic,24(70.6%)were getting better;there are 7 cases with hemorrhagic,3(42.9%)patients were getting better.3.SPECT resultsAll the patients were checked by SPECT after operation.There are 41 Moyamoya hemispheres were treated by improved EDAS,56.1%(23/41)patients were getting better.There are 34 cases with Ischemic,20(58.8%)were getting better;there are 7 cases with hemorrhagic,2(28.6%)patients were getting better.ConclusionImproved EDAS could improve the clinical symptoms?imaging and brain functions of moyamoya disease patients,especially in ischemic patients.Part ? Rat cerebral ischemia and cerebral ischemia/reperfusion protected by Resveratrol(Res)-a study of the medical treatment associated with moyamoya diseaseObjectiveTo explore whether Res could effectively suppress infarct size or improve neurological deficits during acute ischemia or ischemia/reperfusion model in rats.Meanwhile,to explore the protected mechanism of Res during the expression of glutamate transporter was changed.It is necessary for us to find out some drugs with lower side effect and satisfactory effects to inhibit EAA excitotoxicity.Method1.AnimalgroupingRats were divided randomly into sham operation group(Sham group),ischemia group divided into 0.04%propylene glycol solution(10-6 g/kg,B1 group),low dose of Res(10-8 g/kg,C1 group),middle dose of Res(10-7 g/kg,C2 group),high dose of Res(10-6 g/kg,C3 group),ischemia/reperfusion group divided into 0.04%propylene glycol solution(10-6 g/kg,B2 group),low dose of Res(10-8 g/kg,D1 group),middle dose of Res(10-7 g/kg,D2 group),high dose of Res(10-6g/kg,D3 group).The treatment last for 3 day.The middle cerebral artery occlusion model in rats was established by intraluminal thread block for 2h and reperfusion thereafter.2.Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining10 rats were sacrificed 24h after operation in each group,then the brains were quick-freezeed and been cut into even slices.After that,we put the brains into TTC and paraformaldehyde.Finally,we separate the infarcted brains and normal brains based on the color,then weigh the tissues respectively.infarct volume(%)=pale weight/(pale weight+non-pale weight)×100%3.Content of water in brain tissue was measured by wet and dry weight method.Rats were sacrificed 24h after ischemia in each group,then weigh the wet weight of ischemic brain tissue before put that into 100? the oven,and then weigh the dry weight.The ratio of content of water in brain tissue=(wet weight-dry weight)/wet weigh×100%4.The expression of glutamate/aspartate transporter(GLAST)and glutamate transport-1(GLT-1)were observed by immunohistochemical method5 rats were sacrificed in each group.The brain tissues were detected with immunohistochemistry.Then we take photos to these slices and compare the expression of glutamate/aspartate transporter(GLAST)and glutamate transport-1(GLT-1).5.Statistical methodOne-Way ANOVA analysis and SNK-q test was used and so do SPSS 13.0.AP value of<0.05 was considered statistically significant.Result:1.The protected mechanism of Res to neurobehaviorHigh dose of Res treatment significantly ameliorated neurological scores(P<0.05)2.The protected mechanism of Res to infarct volumeThere is difference between C3 and B1,C1,C2(P<0.05);There is different between B2 andD1,D2,D3,also D3 and D1(P<0.05).3.The protected mechanism of Res to content of water in brain tissueIn group C2 and C3,the brain water content reduced compared with group B1(P<0.05).In group D2 and D3,the brain water content reduced compared with group B2(P<0.05).4.The protected mechanism of Res to the expression of GLASTIn group C3,the expression of GLAST increased compared with group B1,C1 and C2(P<0.05).In group D3,the expression of GLAST increased compared with group B2,D1 and D2(P<0.05).5.The protected mechanism of Res to the expression of GLT-1In group C3,the expression of GLT-1 increased compared with group B1,C1 and C2(P<0.05).In group D3,the expression of GLT-1 increased compared with group B2,D1 and D2(P<0.05)..ConclusionRes is effective which can ameliorate the neurological deficit,decrease the infarct size and improve the brain edema caused by acute ischemia or ischemia/reperfusion injury.The mechanism of neuroprotective effects of Res on focal cerebral ischemia/reperfusion injury may by increased the expression of GLAST and GLT-1 in the brain tissue and thus inhibiting the expression of glutamate,so reduced infarction size and the brain edema.ConclusionThis study shows that improved EDAS could improve the clinical symptoms?imaging and brain functions of moyamoya disease patients,especially in ischemic patients.Meanwhile,the mechanism of neuroprotective effects of Res on focal cerebral ischemia/reperfusion injury may by increased the expression of GLAST and GLT-1 in the brain tissue and thus inhibiting the expression of glutamate,so reduced infarction size and the brain edema.As a result,Res do help a lot in protecting the brain in moyamoya desease. |
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