Protecting mechanism of puerarin on the brain neurocyte of rat in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury

The present study was designed to investigate the possible properties of the injured brain neurocytes, the expression of heat shock protein70 (HSP70) and Fas protein after acute local ischemia brain injury and local cerebral ischemia-reperfusion injury in rats and to investigate the protecting mechanism of puerarin on the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury. A rat model of acute local cerebral ischemia was made by ligatting the middle cerebral artery. The rat model of local cerebral ischemia and reperfusion injury was made by ligatting the middle cerebral artery for 30 min then opened for 30 min. Rats of puerarin treating group were injected with puerarin in dose of 30 mg/kg(-1) by intraperitoneal injection 30 min before ischemia. HSP70 and Fas protein expressions in brain tissue were detected by SP method of histochemistry. In addition, dead brain neurocytes were counted and their morphology was observed. The results indicated that puerarin can limit the tissue injury caused by local cerebral ischemia injury through improving expression of HSP70, and limit the tissue injury caused by local cerebral ischemia-reperfusion through decreasing the Fas expression and improving expression of HSP70. On the basis of these results, it may be concluded that puerarin can protect the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury, which may be different according to the different injury mechanism.     

The effects of oxiracetam (CT-848) on local cerebral glucose utilization after focal cerebral ischemia in rats.

The effects of oxiracetam on the reduction of brain metabolism induced by focal cerebral ischemia were investigated by measuring local cerebral glucose utilization (LCGU) in rats 24 hr after left middle cerebral artery occlusion. Focal cerebral ischemia reduced LCGU in the entire ipsilateral cortex, the greatest reduction being in the lateral parts of the frontoparietal cortex. LCGU was slightly reduced in the contralateral cortex; this reduction was considered to be caused by diaschisis. Oxiracetam was administered intraperitoneally for 3 days prior to middle cerebral artery occlusion. In the ipsilateral cortex, LCGU reduction was minimized in the ischemic center areas by oxiracetam at a dose of 400 mg/kg and in more extensive areas, by a dose of 800 mg/kg. Moreover, oxiracetam at a dose of 800 mg/kg enhanced metabolism impaired by diaschisis in the caudal areas of the contralateral cortex. These findings suggest that oxiracetam minimizes the reduction of brain function induced by ischemia and may therefore be useful in the treatment of cerebrovascular disease.     

Comparative study of dilceren (nimodipine) on the cerebral circulation in the intact animals and animals subjected to ischemic brain damage

The influence of the calcium entry blocker dilceren (nimodipine) on the local and regional circulation was studied in rats and cats. In the majority of experiments on intact animals, dilceren increased the local and regional blood flow. However, in some cases, the circulation decreased or remained unchanged, which was accompanied by pronounced hypotension. Administered after global brain ischemia, dilceren improved the cerebral hemodynamics in all experiments.     

Effect of dopamine on the blood circulation and metabolism in the brain during ischemia

In acute experiments on anesthetized cats under blood autoperfusion of cerebral and peripheral vessels with a stable volume of blood during cerebral ischemia there was revealed the vascular and metabolic effects of dopamine on cerebral circulation. Administration of dopamine by perfusion in a dose of 100 micrograms/kg/min for 35 min after ischemia inhibited the development of postischemic hypoperfusion of the brain and also eliminated postischemic hypotension. A significant effect of dopamine on oxidative metabolism of the brain was observed.     

Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats

AIM:To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition. METHODS: Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured. RESULTS: Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia. CONCLUSION: Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.     

The anti-ischemic effects of 3-hydroxypyridine derivatives in cerebrovascular pathology

The effect of the antioxidant mexidol and two new derivatives of 3-oxypyridine, namely LBK-10 and LBK-39 on the circulation of blood and metabolism of the brain in the postischemic period was studied in acute experiments on narcotized cats under conditions of autohemoperfusion of the cerebral vessels with a stable volume of blood. Therapeutic injection of mexidol and LBK in a dose of 20 mg/kg inhibited the development of the no-flow phenomenon and restored the ischemia damaged metabolism in the brain tissues. LBK-10 reduced the lactate content in the blood flowing from the brain and contributed to constriction of the cerebral vessels.     

Characteristics of the effect of different cardiovasotropic preparations on the contractility of separate sections of the myocardium in acute coronary occlusion

In acute experiments on cats, the effect of nitroglycerin (0,5 mg/kg), obsidan (0,5 mg/kg) and adrenaline (0,005 mg/kg) on the contractility of various segments of the myocardium in acute ischemia state was studied. It is shown that nitroglycerin increases the contractility of the border zone and decreases the compensatory hyperfunction of intact myocardial zones. Obsidan reduces the contractility of all the zones and adrenaline suppresses the border zone contractility despite the marked growth of contractile function of the intact zones and of the heart on the whole. The central-ischemic myocardial zone responded weakly to drug action.     

Cardioprotective effect of drugs with antioxidant activity in acute cerebral ischemia

The bioelectric cardiac activity was studied in the experiments on white mice with an acute cerebral blood circulation disorder. It was found that he resulting EEG changes possess a specific character, with the sympathoadrenal system stimulation playing an important role in the acute cerebrocardiac syndrome development. The antioxidant-type agents such as emoxypine (50 mg/kg), mexidol (50 mg/kg), and cytochrome C (10 mg/kg) produce a significant cardioprotective effect in the test animals with experimental cerebral ischemia, which was comparable with the effect of propranolol (obsidane) (0.1 mg/kg).     

The effect of esafosfina on cerebral circulation in intact and ischemized rat brain

The physiological metabolite esafosfina (fructose 1,6-diphosphate) influences the cerebral circulation of intact male rats. Injected intravenously in a dose of 250 mg/kg, esafosfina improved both the blood supply to brain and the local blood flow in the parietal region. Under the conditions of global transient cerebral ischemia, the cerebrovascular effect of the drug tends to increase. Esafosfina produced dissimilar changes in the arterial blood level, which could be explained by various basic status of the test animals. The pronounced cerebrovascular activity of esafosfina plays a key role in its neuroprotector effect.     

羟基红花黄色素A对实验性脑缺血的保护作用

红花为菊科植物红花(Carthamus tinctoriusL.)的干燥花,是传统的活血化瘀类代表药物[1]。红花的化学成分比较复杂,研究表明,红花的花中含有黄酮类、脂肪酸、色素、挥发油以及多炔等化合物[2]。目前认为,红花活血化瘀的主要成分集中在水溶性的黄色素部分;红花黄色素主要成分有羟基红花黄色素A(hydroxysafflor yellow A,HSYA)、红花明苷A、红花明苷B及其他含量较低的成分。在红花黄色素中含量最高且具有活性的成分为羟基红花黄色素A[2]。作者采用经典的大鼠大脑中动脉阻塞性脑缺血模型,观察HSYA对局灶性脑缺血大鼠的行为评分、缺血区面…     

Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats

This study investigated the effects of acetyl-L-carnitine (ALC) in secondarily-induced cerebral chronic ischemia models using rats with permanent ligation of bilateral common carotid arteries (BCCL) and spontaneously hypertensive rats (SHR). Additionally, we used normal aged rats as a primary dementia model. Chronic ALC administration at 100 mg/kg (p.o.) for 4 weeks significantly attenuated neurodegenerative changes. In groups receiving 50 mg/kg or 100 mg/kg, ALC inhibited the active astrocyte increase in cerebral tissues of both BCCL and SHR models. In BCCL rats, ALC administration (50 mg/kg or 100 mg/kg, p.o.) resulted in significant promotion of glutathione levels in brain tissues. We also confirmed behavioral improvement after ALC treatment (100 mg/kg for 8 weeks, p.o.) on learning-memory function using aged rats (18 months old) in a passive avoidance task and preservation of CA1 pyramidal neurons was coincided on histopathological observation. In conclusion, chronic ALC administration may ameliorate cerebral ischemia progress after a cerebrovascular disorder as well as spontaneous ageing-related cerebral dysfunction via hippocampal protection.     

Effect of ketamine on cerebral circulation of intact and ischemic animals

The influence of ketamine on the local cerebral circulation was studied in intact rats and under the conditions of global brain ischemia. The drug increased the local blood flow in intact rats. Despite pronounced hypotension accompanying the global brain ischemia, ketamine helped maintenance of the cerebral circulation.     

油酰乙醇胺在小鼠急性局灶性脑缺血再灌注损伤中的作用及机制

目的研究油酰乙醇胺(OEA)在脑缺血再灌注损伤中的作用及机制。方法线栓法制备小鼠大脑中动脉栓塞模型,缺血90 min后再灌注。应用HPLC-MS/MS方法测定脑组织内OEA的含量。给予OEA(5,10,40 mg/kg,ig)或OEA水解酶抑制剂URB597(1 mg/kg,ig),观察其对小鼠急性脑缺血再灌注损伤的影响。测定脑组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)及过氧化氢酶(CAT)的活性。观察MK886对OEA抗脂质过氧化损伤的影响。结果脑缺血再灌注后6 h,损伤侧脑内OEA含量开始升高,再灌注后24 h升高最明显。脑缺血再灌注后给予OEA(40 mg/kg)或URB597(1 mg/kg)可减少神经功能缺失评分,减小脑梗死体积,减轻脑水肿程度。OEA可减少脑内MDA含量,增加抗氧化酶SOD的活性。OEA这一抗氧化作用可被MK886所取消。结论脑缺血再灌注可增加脑内OEA的含量,OEA通过激动PPARα,减轻脂质过氧化损伤发挥抗脑缺血再灌注损伤作用。     

Dopamine enhancement of the cerebral microcirculation in a local ischemic lesion

The effect of dopamine on the local cerebral blood flow in parietal brain cortex region of rats was studied in conditions of local ischemia induced by middle cerebral artery occlusion. Registration of the local cerebral blood flow was performed on a ALF-21 laser doppler flowmeter ("Transonic System Inc.", USA). Dopamine produces a pronounced effect on cerebral circulation in conditions of local brain ischemia thus causing a significant increase in blood flow both in ischemic and intact hemispheres. The effect is observed both in the acute stage of ischemic brain injury and in the remote period of brain ischemia.     

DY-9760e, a calmodulin antagonist, reduces brain damage after permanent focal cerebral ischemia in cats

DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), a calmodulin antagonist, provides protection against Ca(2+) overload-associated cytotoxicity and brain injury after cerebral ischemia in rats. In this study, we assessed the effect of DY-9760e on ischemic infarct volume in cats subjected to permanent focal cerebral ischemia. DY-9760e was infused for 6 h, beginning 5 min after occlusion of the middle cerebral artery. The infarct volume was measured at the end of drug infusion. DY-9760e, at the dose of 0.25 but not 0.1 mg/kg/h, significantly reduced cerebral infarct volume without affecting any physiological parameters, and its protective effect was mainly evident in the cerebral cortex, where the penumbra, a salvageable zone, exists. The present study demonstrates that DY-9760e protects against brain injury after focal ischemia in a gyrencephalic animal as well as in the rodents reported previously and suggests its therapeutic value for the treatment of acute stroke.     

水杨酸镁对脑缺血再灌注损伤的保护作用

目的：观察水杨酸镁对缺血再灌注造成的脑损伤的保护作用。方法：采用四动脉结扎法，制作大鼠全脑缺血再灌注模型。动物随机分成伪手术、再灌注、尼莫地平２ｍｇ／ｋｇ、水杨酸镁５ｍｇ／ｋｇ及１０ｍｇ／ｋｇ组共５组，于缺血前，再灌注前及再灌注过程中各ｉｖ给药１次。结果：缺血４０ｍｉｎ再灌注１ｈ后，脑水份从７９．０％升到８３．２％，脑钙含量由１７３升到２３９μｇ／ｇｄｗ，丙二醛含量从１５．６升到２４．６μｍｏｌ／ｇ蛋白质，乳酸脱氢酶含量由２０．７降到１１．２ＫＵ／ｇ蛋白质。尼莫地平和水杨酸镁均能减弱上述改变，并改善再灌注期间脑电图的改变。结论：水杨酸镁保护脑组织，其机制与其钙拮抗作用有关     

益气熄风胶囊对大鼠局灶性脑缺血再灌注损伤的保护作用

目的研究益气熄风胶囊防治大鼠局灶性脑缺血再灌注损伤的作用以及其作用机制。方法将SD大鼠随机分为假手术组、模型组、尼莫地平片(30 mg/kg)组和益气熄风胶囊0.771 8、1.543 5、3.087 0、6.174 0 g/kg组,每个组再分为脑梗死率检测、病理学研究2个亚组。益气熄风胶囊于造模前ig给药,1次/d,连续7 d;假手术组和模型组给予生理盐水,给药体积均为10 m L/kg。于第7天给药后30 min制造大脑中动脉闭塞(MCAO)模型。大脑中动脉阻断3 h后,进行再灌注。假手术组仅在动脉处备线处理,待给予生理盐水后去线即可。缺血再灌注后24 h后TTC染色法测定脑梗死体积,计算脑梗死率。缺血再灌注24 h时计算脑指数和脑含水量。各组大鼠在脑缺血再灌注后3、24 h进行神经功能评分。采用苏木素、伊红进行染色,光镜下观察各组大鼠脑组织的病理形态。采用甲苯胺蓝尼氏染色法检测尼氏小体表达情况,观察脑组织尼氏小体数量;采用免疫组化染色SP法测定i NOS蛋白的平均吸光度值,观察大鼠脑组织i NOS蛋白表达情况。结果益气熄风胶囊1.543 5、3.087 0 g/kg对局灶性脑缺血再灌注引起大鼠脑梗死率增大有明显降低作用(P0.05),而益气熄风胶囊0.771 8、6.174 0 g/kg组大鼠脑梗死率无明显变化。益气熄风胶囊0.771 8、1.543 5、3.087 0、6.174 0 g/kg组大鼠脑指数和脑含水量无明显变化。造模后3 h益气熄风胶囊0.771 8、3.087 0、6.174 0 g/kg神经行为学评分明显增加(P0.05、0.01),对局灶性脑缺血再灌注而引起大鼠神经功能损伤症状有改善作用,而益气熄风胶囊1.543 5 g/kg的作用不明显。与模型组比较,益气熄风胶囊1.543 5 g/kg组大鼠脑组织的灰质病变、白质病变、脑膜、室管膜病变均明显减轻(P0.01),尼氏染色计数平均吸光度值显著增加(P0.01),脑组织中i NOS蛋白表达水平有降低的趋势,但是不具有统计学意义。结论益气熄风胶囊对大鼠局灶性脑缺血再灌注损伤具有明确的保护作用,其作用机制可能与脑组织病理病变减轻和尼氏小体数量增加有关。     

Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression

Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1mg/kg in 200 μL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 μg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37) (4 × 10(-8)mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression.     

左旋四氢巴马汀对大鼠脑缺血再灌注损伤后p53表达的影响

目的观察左旋四氢巴马汀(L-THP)对大鼠局灶性脑缺血再灌注损伤后神经细胞凋亡及p53表达的影响。方法采用线栓法阻塞大鼠大脑中动脉(MCAO)建立局灶性脑缺血实验模型,于MCAO前30min腹腔注射L-THP,观察不同浓度L-THP(5、10、20mg/kg)对脑缺血再灌注损伤后大鼠脑梗死体积的改变;免疫组化法检测p53的表达改变;TUNEL法检测神经细胞凋亡的数量改变。结果①各用药组脑梗死体积明显小于缺血再灌组;②与缺血再灌组相比,各用药组p53蛋白表达明显下降;③各用药组凋亡细胞均较缺血再灌组明显减少。结论L-THP可能通过抑制p53表达以减少神经细胞的凋亡。     

Effects of the new eburnamenine derivative RU 24722 on EEG recovery and cerebral energy metabolism after complete ischemia

The influence of a new eburnamenine derivative RU 24722 [(3 beta, 14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin -14-ol] on post-ischemic EEG recovery was studied in N2O anesthetized rats subjected to 1 min of global-compression cerebral ischemia. RU 24722 was compared with vincamine, dihydroergotoxine mesylate and nicergoline. Treatment with RU 24722 (2 mg/kg i.v.) significantly decreased the EEG recovery time and increased the electrocortical activity during the first phase of the post-ischemic recovery. Vincamine (2 mg/kg i.v.), dihydroergotoxine mesylate (0.5 mg/kg i.v.) and nicergoline (0.5 mg/kg i.v.) were devoid of activity. In an attempt to elucidate its mechanism of action, the influence of RU 24722 on changes in the cerebral metabolic energy reserves was studied in mouse brain after different periods of decapitation ischemia. The changes occurring during the first 10 s of ischemia were used to calculate the baseline cerebral metabolic rate (CMR). The activity of RU 24722 was compared with that of vincamine and pentobarbital. RU 24722 (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilisation and lactate production. Vincamine (10 mg/kg i.p.) had no effect on cerebral energy substrates. Pentobarbital (100 mg/kg i.p.) markedly increased the tissue concentration of glucose and phosphocreatine and decreased lactate levels before and after ischemia. The improvement of EEG recovery suggests that RU 24722 may be therapeutically effective in cerebral insufficiency, and the decreased brain energy demand may be one of the mechanisms by which RU 24722 has a protective effect against cerebral ischemic damage.