In recent years, the incidence of cerebrovascular disease in China has been increasing year by year. Acute cerebral infarction accounts for about 70% of all strokes [1] with a high rate of death and disability. Therefore, research on cerebral ischemia has received increasing attention. However, there has been no breakthrough in the field of treatment, and the search for new treatment methods and approaches has become the most urgent and important research topic. This paper presents a review of the current status and progress of domestic and foreign research in recent years.
1.Acute treatment
1.1 First-aid principles
(1) The treatment of cerebral ischemia should remove the thrombus in the artery as early as possible, release the obstruction, and rapidly improve or increase the blood supply to the ischemic area. “Time is brain”, within the time window, effectively take thrombolysis and reflow to control cerebral edema and prevent brain herniation; reduce brain metabolism and protect brain cells; dilute blood, reduce blood viscosity and improve circulation; reduce complications; make the mortality and disability rate decrease.
(2) Assessment steps of the emergency plan:
①Confirm and diagram cerebral ischemia;
(ii) Predict the prognosis of untreated cerebral ischemia;
(3) Assess the viability and possible reversibility of the ischemic tissue;
④Predict the outcome of treatment;
⑤ Selecting treatment options.
1.2 “Time window” treatment Lysis of thrombus and restoration of blood supply is one of the most effective treatment measures recognized internationally. In 1991, Bamford et al. proposed the OCSP staging method to guide clinical treatment. The greatest advantage of this method is that it does not depend on CT and MRI findings, and can rapidly classify four subtypes according to the patient’s whole brain symptoms and focal brain damage symptoms in a very short time, indicating the size and location of occluded vessels and infarct foci, which buys time for thrombolysis. The timing of thrombolysis: most scholars at home and abroad believe that it should be within 3-6 h. Restoring blood flow after more than 6 h can cause reperfusion injury, secondary hemorrhage and cerebral edema. ninds reports that the efficiency is 51.4% within 6 h and 8% within 24 h. Wise believes that within 24-72 h, there is still a hope that the hemispheric zone can be saved.
1.3 Thrombolytic agents
1.3.1 Urokinase (UK) can activate fibrinogen directly and is effective. 1-1.5 million U (max. 3.45 million U), 10% of which is administered intravenously for the first time and the rest is administered intravenously in GS. Intra-arterial or intra-arterial catheter thrombus injection of urokinase within 6h for the treatment of middle cerebral artery (MCA) trunk and major branches, vertebral artery, and basilar artery blockage can lead to arterial recanalization in a significant proportion of patients, resulting in rapid improvement. Arterial administration ranges from 180,000 to 1.2 million U.
1.3.2 Streptokinase (SK) has been discontinued in recent years as a result of multicenter trials in Europe, the United States and Australia, which concluded that the drug increases mortality. Urokinase, streptokinase bleeding complications, according to literature reports parenchymal bleeding accounted for 9.3% to 32.5%.
1.3.3 The 2nd generation thrombolytic agent atrapase (TPA) is a serine protease present in vascular endothelial cells, also known as tissue fibrinolytic activator, which weakens fibrinogen activator inhibitor (PAI) and promotes fibrinogenesis and dissolves thrombus. The usual dosage of t-PA ≤ 0.85mg/kg, and arterial administration of t-PA 20-100mg/time. The third generation of recombinant tissue-type fibrinogen activator rt-PA is commonly used, which can directly catalyze fibrinogen into fibrinolytic enzyme and dissolve thrombus, with the common dosage of 10-100mg and arterial administration of 20-200mg.
1.4 Fibrin-lowering therapy is commonly used to degrade fibrinogen, inhibit erythrocyte aggregation, enhance vascular permeability and deformability of erythrocytes, reduce platelet adhesion, and inhibit thrombus formation. It should be applied within 6h of the onset of disease, with the initial dosage of 10BU of fibrinogen, followed by 5BU of intravenous drip every other day for 3 times. The first 10 BU of Dongling pure thromboxane should be added to 100 ml of NS in a sedative drip (for more than 30 min), and the second and third days should be given once more with 5 BU of Dongling pure thromboxane, for a total of 3 times.
1.5 Anticoagulation therapy
(1) Anti-platelet coagulation drugs: the main representatives are:
①Aspirin has been proven to have preventive effect on ischemic cerebrovascular disease.
(2) Thromboxane A 2 (TXA 2 ) synthase inhibitors, Ridogrel (Lidogrel), Ozagrel (OKY-046, Ozagrel), Isbogrel (CV-4151), etc. Imura and Terashital et al. found that TXA 2 synthase inhibitors, Isbogrel and Ozagrel (OKY-046, Ozagrel), and Isbogrel (CV-4151), have the ability to inhibit platelet coagulation and thrombosis by improving the balance between TXA 2 and PGI 2. The antithrombotic effect of Isbogrel and Ozagrel was stronger than that of aspirin and Ticlopidine, and the antithrombotic effect of Isbogrel was 10 times that of Ozagrel, and it reduced cerebral edema and brain tissue damage after cerebral ischemia. inhibitors ameliorated the effects of delayed neuronal necrosis.