Permanent cerebral hypoperfusion: ‘preconditioning-like' effects on rat energy metabolism towards acute systemic hypotension

Chronic cerebrovascular disorders are often complicated by additional temporary ischaemic insults, resulting in substantial deterioration of brain energy metabolism. In the present study, chronic limitations of oxygen supply were induced in Wistar rats by 2 weeks of permanent bilateral common carotid artery occlusion (2-vo) to initiate a ‘preconditioning-like' effect that protects rat brain energy metabolism against further acute systemic hypotension (15 min). Haemodynamic parameters, arterial blood gases and body temperature were monitored. Energy metabolites were determined in rat parietotemporal cerebral cortex: adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP), adenosine 5′-monophosphate (AMP), phosphocreatine (PCr), and adenosine by the high-pressure liquid chromatography (HPLC) technique and lactate spectrophotometrically. After 2 weeks, permanent 2-vo led to a significant decrease in the concentrations of cortical tissue ATP and PCr, from 3.06±0.48 to 2.09±0.28 and from 4.27±0.63 to 3.35±0.41 μmol/g, respectively. These changes were associated with a two-fold increase in AMP and adenosine. Acute systemic hypotension alone (non-preconditioning) reduced ATP and PCr drastically, to 0.97±0.51 and 1.76±1.23 μmol/g. Tissue concentrations of lactate, AMP, and adenosine were markedly increased, three- to five-fold, in ‘non-preconditioned' brain tissue. In contrast, after 2 weeks of 2-vo acute hypotension did not significantly alter the cortical energy state any further. The effects of preconditioning on tissue ATP and PCr were most pronounced at 5 min and 48 h after reperfusion. In conclusion, permanent 2-vo seems to activate compensatory mechanisms, which effectively protect the rat's cortical energy metabolism against an additional ischaemic attack (‘preconditioning-like' effect).     

磁共振弥散/灌注加权成像确认局灶脑缺血半暗带的实验研究

目的　探讨超急性期确认局灶脑缺血半暗带的范围和演变规律。方法　用易卒中型肾血管性高血压大鼠(RHRSP)行左侧腔内线栓MCAO术 ,分别在闭塞 12h内的不同时间点及再灌注 48h后行T2 加权成像 (T2 WI)、磁共振弥散加权成像 (DWI)和磁共振灌注加权成像 (PWI)。将大鼠处死后行TTC染色 ,比较在闭塞不同的时间点上在两次T2 WI和DWI上病灶的演变和TTC染色上梗死灶的改变。结果　DWI在闭塞 30min时显示出确切的病灶 ,而T2 WI要在 3h以后才能显示出病灶 ;自 30min至 6h ,DWI所显示的病灶持续扩大 ,可逆性部分占首次DWI上病灶的百分比 (%RP)逐渐缩小 ,最终为负数 ;PWI在MCAO闭塞的即刻即在时间 信号强度曲线上表现为最大下降幅度的减小 ,复通后上升 5 0 %以上 ;半暗带部分水的表面弥散系数值 (ADC)为 (0 5 6± 0 0 2 )× 10 -5cm2 /s。结论　DWI能在超急性期 (3h以内 )显示出缺血病灶 ,根据梗死中心和梗死周边的ADC值的不同可以分辨出可逆性和不可逆性损伤的缺血组织 ;本模型的缺血半暗带存在的时间为6h。     

噻氯匹啶与阿司匹林预防缺血性脑卒中前瞻性随机对照研究

目的 观察噻氯匹啶（ＴＩＣ）预防缺血性卒中（ＩＳ）的临床疗效及安全性,并与小剂量阿司匹林（ＡＳＡ）预防ＩＳ的疗效作对照。方法 选择３２９例ＴＩＡ与轻型ＩＳ病人,随机分为ＴＩＣ组（１６５例）与ＡＳＡ组（１６４例）。ＴＩＣ组口服ＴＩＣ ２５０ｍｇ／ｄ,ＡＳＡ组口服ＡＳＡ ５０ｍｇ／ｄ,禁服其他抗血小板药物。每例病人１～２个月随访１次,共随访６～１８个月。结果 ＴＩＣ组卒中死亡率（８．３％）低于ＡＳＡ组     

旋肱后血管为蒂肱骨骨膜瓣移位的应用解剖

目的 :为肱骨头缺血性坏死提供一种新的显微外科修复方法。方法 :在 3 2侧经动脉内灌注红色乳胶的成人上肢标本上 ,解剖观测了旋肱后动脉的起始、走行、分支、分布及吻合情况 ,设计了以旋肱后血管为蒂肱骨骨膜瓣移位术。结果 :旋肱后动脉在出四边孔即距肱骨大结节顶点下 5 .6± 0 .9cm处发大结节骨膜支和三角肌肌支 ,本干循肱骨外科颈后面向前行并与旋肱前动脉吻合。大结节骨膜支起点管径为 1.2± 0 .2mm ,向大结节顶点走行 ,沿途分 4～ 5条侧支呈扇形分布于大结节后外侧面骨膜 ,供骨面积可达 3 .0cm× 5 .0cm。结论 :以旋肱后血管为蒂肱骨骨膜瓣移位可用于修复肱骨头缺血坏死 ,方法简便实用。     

平板运动试验时的心率血压反应与缺血阈值

目的 研究平板运动试验时的心率血压反应与缺血阈值。方法 选择不典型胸痛的病人５７６例,男３６８例,女２０８例,年龄为４０￣６０岁之间,采用Ｍａｒｑｕｅｔｔｅ ＭＡＸ－１活动平板,Ｂｒｕｃｅ修正方案,运动过程中监测心率、血压的变化。结果 所有检者均已达到最大预计心率的８５％以上,但运动试验阳性组所达到的心率、及运动时间（Ｔ）低于其他组,最大ＳＴ段／心率斜率（ｍａｘｉａｌ ＳＴ／ＨＲ ｓｌｏｐｅ）、代     

Potential of Rheopheresis for the Treatment of Acute Ischemic Stroke When Initiated Between 6 and 12 Hours

Abstract: Improvement of hemorheology is one of the most important approaches in the treatment of acute ischemic stroke. We investigated the influence of extracorporal rheopheresis (ER) on cerebral blood flow in patients with acute ischemic stroke and evaluated its therapeutic effect. Thirty‐three patients (rheopheresis group, 17; control group, 16; mean age 64 ± 10 years) with acute ischemic stroke were included in our prospective randomized trial. The first treatment was started within 12 h after onset of symptoms, and treatment was repeated 3 times at an interval of 24 h. Hemorheological parameters were measured before and after each session. The cerebral blood flow was analyzed using ^99mTc‐ECD‐SPECT. The functional and neurological outcomes were determined by follow‐up investigations after 3 months. The hemorheological parameters were significantly different between the rheopheresis group (18% decrease of plasma viscosity, 55% decrease of red blood cell aggregation) and the control group (no decrease of both parameters). The single photon emission computed tomography (SPECT) analysis showed early reperfusion in 35% of the patients treated with rheopheresis and in 37% of the control group (NS). There were no differences in the neurological outcomes between the 2 groups. Extracorporal rheopheresis is practicable and safe. It rapidly and consistently improved the hemorheological parameters. Although this did not impact on cerebral perfusion or clinical outcome in patients with acute ischemic stroke in this report, we propose that ER deserves to be further evaluated by initiating the first treatment within 6 h post‐insult.     

大鼠脑缺血预处理神经细胞凋亡的研究

目的 探讨缺血预处理对神经细胞凋亡的影响。方法 采用四动脉法大鼠全脑缺血模型,２１只Ｗｉｓｔａｒ大鼠,腹腔注射戊巴比妥钠麻醉。大鼠分四组,Ａ组,假手术对照组（ｎ－５）,未予脑缺血处理;Ｂ组,预处理组对照组（ｎ＝５）,于３ｍｉｎ全脑缺血后未再次缺血,Ｃ组,预处理缺血组（ｎ＝５）,于３ｍｉｎ全脑缺血,再灌２４ｈ后,再次全脑缺血１０ｍｉｎ全脑因后未再次缺血,Ｃ组,预处理缺血组ｎ＝５）,于３ｍｉｎ全脑缺血     

The liver protective effect of ischemic preconditioning may be mediated by adenosine

Abstract We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8‐phenyltheophylline (8‐PT). Anesthetized Wistar rats were treated as follows: 1. nonischemic controls, 2. ischemic controls: 60 min of clamping of the common hepatic artery followed by 60 min reperfusion, 3. IPC: 10 min ischemia followed by 15 min reperfusion, prior to the identical ischemia‐reperfusion (IR) period as in group 2, 4. 8‐PT + IPC: 8‐PT 10 mg/kg i. v. was given 10 min prior to the identical procedure as in group 3. The peripheral liver blood flow was monitored by laser‐Doppler flowmetry. Blood alanine aminotransferase (ALT) was analyzed once every 60 min. IPC significantly reduced impairment of liver blood flow, as well as ALT increase during reperfusion. This effect was abolished by pretreatment with 8‐PT. Adenosine appears to be a crucial effector in IPC. Clinical studies need to be undertaken to explore a possible effect of IPC in liver transplantation.     

急性脑梗死动脉溶栓术后脑出血与"脑染色"的鉴别诊断

目的研究急性脑梗死早期(6 h之内)动脉溶栓治疗后即刻脑CT征象及脑出血危险因素.方法对82例急性脑梗死早期溶栓治疗后的患者进行头颅CT检查,观察即刻、4～6 h、24 h脑CT表现.结果即刻CT扫描出现27例高密度区,包括脑组织染色8例,其中神经核团染色5例,脑灰质染色3例;溶栓后脑出血15例;亚急性脑梗死区脑组织染色4例.CT早期缺血改变及较低的ESS评分是脑动脉溶栓术后脑出血的主要危险因素,它们的相对危险度分别为8.33和11.35.结论急性脑梗死动脉溶栓后即刻脑CT显示的脑组织染色是由于闭塞的脑血管部分或全部再通,引起缺血-再灌流损伤,进一步损伤血管内皮,使血管通透性增加,局部血脑屏障受损,含对比剂的血液内液体成分渗到脑组织间隙所致,使血管再通区受损伤的灰质或神经核团的脑组织染色,白质不染色.随着对比剂在体内的减少,染色在几小时后逐渐变淡,此种表现是闭塞的脑血管再通前局部脑组织已出现缺血性脑梗死的征象,勿误认为脑出血征象.     

Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy

As a multi-target drug to treat ischemic stroke, N-butylphthalide (NBP) is extremely water-insoluble and exhibits limited oral bioavailability, impeding its wide oral application. Effective treatment of ischemic stroke by NBP requires timely and efficient drug exposure, necessitating the development of new oral formulations. Herein, liposomes containing biosurfactant sodium cholate (CA-liposomes) were systemically investigated as an oral NBP delivery platform because of its high biocompatibility and great potential for clinical applications. The optimized liposomes have a uniform hydrodynamic size of 104.30 ± 1.60 nm and excellent encapsulation efficiency (93.91 ± 1.10%). Intriguingly, NBP-loaded CA-liposomes produced rapid drug release and the cumulative release was up to 88.09 ± 4.04% during 12 h while that for NBP group was only 6.79 ± 0.99%. Caco-2 cell monolayer assay demonstrated the superior cell uptake and transport efficiency of NBP-loaded CA-liposomes than free NBP, which was mediated by passive diffusion via transcellular and paracellular routes. After oral administration to rats, NBP-loaded CA-liposomes exhibited rapid and almost complete drug absorption, with a t_max of 0.70 ± 0.14 h and an absolute bioavailability of 92.65% while NBP suspension demonstrated relatively low bioavailability (21.7%). Meanwhile, NBP-loaded CA-liposomes produced 18.30-fold drug concentration in the brain at 5 min compared with NBP suspension, and the brain bioavailability increased by 2.48-fold. As expected, NBP-loaded CA-liposomes demonstrated significant therapeutic efficacy in a middle cerebral artery occlusion rat model. Our study provides new insights for engineering oral formulations of NBP with fast and sufficient drug exposure against ischemic stroke in the clinic.