We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h~48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.

大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral isch-emia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin signiifcantly im-proved neurological deifcit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-αin the ischemic region. These data indicate that puerarin exerts an anti-inlfammatory protective effect on brain tissue with ischemia/reperfusion damage by down-regulating the expression of multiple inlfammatory factors.

The traditional Chinese medicine Buyang Huanwu Decoction has been shown to improve the neu-rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. In this study, we established a rat model of cerebral ischemia by middle cerebral artery occlusion and intragastrical y administered 5 g/kg Buyang Huanwu Decoction, once per day, for 1, 7, 14 and 28 days after cerebral ischemia. Immunohistochemical staining revealed a number of cel s positive for the neural stem cel marker nestin in the cerebral cortex, the subven-tricular zone and the ipsilateral hippocampal dentate gyrus in rat models of cerebral ischemia. Buyang Huanwu Decoction significantly increased the number of cel s positive for 5-bromodeoxyuridine (BrdU), a cel proliferation-related marker, microtubule-associated protein-2, a marker of neuronal differentiation, and growth-associated protein 43, a marker of synaptic plasticity in the ischemic rat cerebral regions. The number of positive cel s peaked at 14 and 28 days after intragastric administration of Buyang Huanwu Decoction. These findings suggest that Buyang Huanwu Decoction can promote the proliferation and differentiation of neural stem cel s and hance synaptic plasticity in ischemic rat brain tissue.

It is necessary to investigate the longitudinal tensile mechanical characteristics of the middle cere-bral artery and the fetal umbilical vein prior to applying fetal umbilical vein transplantation for repair of injured middle cerebral artery. Fifteen fresh fetal umbilical vein specimens and 15 normal human fresh cadaver middle cerebral artery specimens were col ected for longitudinal tensile testing at the speed of 0.5 mm/min and at normal human temperature. The results showed that under 16.0 kPa physiological stress, the strain value of fetal umbilical vein specimens was larger, while the maximal stress and elastic modulus values were less than those of middle cerebral artery specimens. Our findings indicate that fetal umbilical vein has good elastic properties and the stress-strain curve of the fetal umbilical vein is similar to that of the middle cerebral artery. Fetal umbilical vein transplan-tation can, therefore, potential y repair the injured middle cerebral artery.

Detailed knowledge of motor outcomes enables to establish proper goals and rehabilitation strate-gies for stroke patients. Several previous studies have reported functional or motor outcomes in patients with a middle cerebral artery territory infarct. However, little is known about motor outcome in patients with a complete middle cerebral artery territory infarct. In this study, we investigated the motor outcomes in 23 patients with a complete middle cerebral artery territory infarct. Al of these patients received comprehensive rehabilitative management, including movement therapy and neuromuscular electrical stimulation of the affected finger extensors and ankle dorsiflexors, for more than 3 months. Motor outcomes were measured at 6 months after stroke onset using the Medical Research Council, Motricity Index, the modified Brunnstrom Classification, and Functional Ambula-tion Category scores. The motor function of the lower extremities was found to be better than that of the upper extremities. After receiving rehabilitation treatments for 3-6 months, about 70%of these patients were able to walk independently (Functional Ambulation Category scores>3), but no pa-tient achieved functional hand recovery.

Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the ce-rebel um, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffu-sion-weighted imaging showed that the area of infarction core gradual y increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initial y in-creased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion coefficient value in the infarction core and remote bilateral cerebel um both gradual y decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at mote regions (cerebel um) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coeffi-cient values and diffusion weighted imaging can be used to detect early diaschisis.

Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrical y administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Wil ebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton.

The transplantation of artificial blood vessels with<6 mm inner diameter as substitutes for human arterioles or veins has not achieved satisfactory results. Umbilical vein has been substituted for ar-tery in vascular transplantation, but it remains unclear whether the stress relaxation and creep tween these vessels are consistent. In this study, we used the fetal umbilical vein and middle cere-bral artery from adult male cadavers to make specimens 15 mm in length, 0.196-0.268 mm in nica media thickness, and 2.82-2.96 mm in outer diameter. The results demonstrated that the stress decrease at 7 200 seconds was similar between the middle cerebral artery and fetal umbilical vein specimens, regardless of initial stress of 18.7 kPa or 22.5 kPa. However, the strain increase at 7 200 seconds of fetal umbilical veins was larger than that of middle cerebral arteries. Moreover, the stress relaxation experiment showed that the stress decrease at 7 200 seconds of the fetal umbilical vein and middle cerebral artery specimens under 22.5 kPa initial stress was less than the decrease in these specimens under 18.7 kPa initial stress. These results indicate that the fetal umbilical vein has appropriate stress relaxation and creep properties for transplantation. These properties are advantageous for vascular reconstruction, indicating that the fetal umbilical vein can be transplanted to repair middle cerebral artery injury.

改良标准外伤大骨瓣减压术治疗恶性大脑中动脉梗死

恶性大脑中动脉梗死(malignant middle cerebral artery infarction,mMCAI)是由大脑中动脉主干阻塞所致的大面积脑梗死,梗死的范围为大脑半球中3/5,由于脑组织损害范围较大,临床上除表现脑梗死的症状外,还伴有严重的意识障碍和急骤的颅内压增高.对于部分mMCAI的患者,经积极内科治疗后病情仍进行性加重发生脑疝而死亡,去骨瓣减压术可明显降低经内科治疗无效的mMCAI患者的死亡率和致残率,是常规内科治疗的必要补充[1].我科采用改良标准外伤大骨瓣减压术治疗mMCAI26例,效果良好,报告如下.

去骨瓣减压术治疗恶性大脑中动脉脑梗死预后影响因素及手术指征探讨

恶性大脑中动脉脑梗死(Malignant middle cerebral artery territory infarction,MMCI)是指大脑中动脉(MCA)主干或者颈内动脉起始段闭塞导致的MCA供血区大面积脑梗死,此病病情凶险,50%～78%的患者死于脑疝[1].MMCI约占缺血性卒中的2%～10%,单纯保守治疗的死亡率可高达79%[2].近期欧洲的3项随机对照试验研究显示去骨瓣减压术可明显降低死亡率,改善患者预后[3～5].去骨瓣减压术可将死亡率由80%降至30%[6～9].由于缺乏严格的前瞻性随机对照试验证据,手术时机各研究单位采用的标准不一致,对临床预后的判断缺乏科学的判定标准.本文就去骨瓣减压术治疗MMCI预后影响因素及手术指征予以综述.

氙气在小鼠大脑中动脉短暂性梗塞模型上的神经元保护作用

麻醉气体,其特性包括相对较高的心血管安全性(同等或优于传统麻醉药),与其他大多数气体相比较好的药物动力学或药效学特点.越来越多的临床和实验研究表明,氙气作为一种气体麻醉药,具有镇痛、诱导苏醒迅速和对心血管影响小的特点.另外,由于其对环境影响小,因此适用于吸入麻醉.但是,由于其价格昂贵,在临床应用中也因此受到了限制.

单侧MCA重度狭窄或闭塞患者的颅内血流动力学与侧支循环的TCD探讨

大脑中动脉(middle cerebral artery MCA)重度狭窄或闭塞通常导致脑内血流动力学障碍,其引发脑卒中的危险性很大.有研究表明MCA病变侧支循环的开放与早期神经功能转归有关、对脑组织有保护作用.TCD可以间接评价MCA病变侧支循环情况,表现为同侧ACA或(和)PCA血流速度升高,但目前尚缺乏统一标准.本文入组TCD诊断MCA重度狭窄(狭窄>70%)或闭塞,并经DSA证实的缺血性卒中患者,检查其颅内的血流状态,分析由此引起的脑血流动力学参数变化,来探讨脑血流速度变化与MCA病变后侧支循环之间的关系,寻求判断侧支开放的标准.

INTRODUCTION　The “ischemic tolerance in brain” fou nded by Kitagawa et al[1] is an ideal model to investigate the mechanisms of cerebral ischemic damage and neuroprotection. But exposing patients to brief ischemic events before an antici pated cerebral ischemia occurs seems difficult and unacceptable in clinical practice. Therefore, some investigators studied the possibility of chemical preconditionin g which mimics ischemic preconditioning, and demonstrated that some chemicals coul d induce the ischemic tolerance in brain [2]. However, the clinical applic ation of these chemical substances is yet to be elucidated because of their toxicity or side ef fects.　　Recently, isoflurane and sevoflurane have been proved to be able to mimic ischemic preconditioning in myocardial ischemia[3-6]. Whether they could also induce the same effects in brain has not been reported yet. Therefore, the present stud y was undertaken to testify if isoflurane could induce ischemic tolerance in brain on middle cerebral artery occlusion (MCAO) rat model.

Objective:　To investigate the value of transcranial Doppler (TCD) ultrasonography in evaluating the outcome of severe traumatic brain injury and to correlate the TCD values with intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring. 　　Methods:　A prospective study was conducted to evaluate the contribution of TCD ultrasonography to neurological outcome in a series of 96 severe traumatic brain injury patients. The quantitative variables of TCD ultrasonography included the mean blood flow velocity of the middle cerebral artery (MCA) and pulsatility index within the first 24 hours of admission. The ICP and CPP values were also recorded. Outcome in 6 months postinjury was evaluated using the Glasgow Outcome Scale (GOS 4-5 was considered as “good” and GOS 1-3 as “poor”).　　Results:　The mean blood flow velocity of the MCA was larger than 40 cm/s in 30 (51%) patients with good outcome whereas it was less than 40 cm/s in 27 (73%) patients with poor outcome (P<0.025). The mean PI in cases of good outcome (34 patients, 57%) was lower than 1.5 whereas in poor outcome (30 patients, 83%) was higher than 1.5 (P<0.001). The correlations of ICP and CPP to pulsatility index were statistically significant (P<0.01). 　　Conclusions:　TCD ultrasonography is valid in predicting the patients outcome of 6 months and correlates significantly with ICP and CPP values when it is performed in the first 24 hours of severe traumatic brain injury.