逆灌注脑保护技术研究与进展

脑逆灌注技术（RCP）是一种较新的脑保护措施，它从静脉系统逆行灌注氧合血到脑组织，在心血管手术中体循环停止时，利用该技术可向大脑提供富氧血，延长脑缺血耐受时限，为手术赢得更充裕的时间，同时它也可在脑卒中时缩短脑再灌流时间，从而延长脑卒中治疗的时间窗，提高药物治疗的疗效。本概述了该技术近20年的发展状况及临床应用，并对未来的发展方向进行了展望。     

脑氧代谢的影像学测定方法研究

随着年龄的不断增长,脑血管疾病的发生率越来越高,对于脑血管疾病的血运动力学的研究越来越重要,能更好的认识脑血管疾病,从而能更早的发现、治疗及预防脑血管疾病。判断血液动力学的参数有脑血流量﹑灌注压、颅内压、氧摄取率、脑脊液和脑氧代谢率,正常状态下脑摄取与脑利用之间处于动态的平衡,当出现脑血管疾病时各参数之间将会出现变化,对于参数的研究能敏感的反应脑氧代谢的差异,从而更好的指导临床,更早的对疾病进行治疗,延缓恶化,同时为临床科研项目提供更加重要的线索。     

小型幼猪体外循环模型灌注流量对脑血流灌注的影响

目的建立幼猪体外循环(cardiopulmonary bypass,CPB)模型,观察CPB灌注流量发生改变期间,脑灌注流量和局部脑氧饱和度(regional cerebral oxygen saturation,rSO_2)的变化,从而探索CPB灌注流量对脑血流量自我调节的影响,以期为婴幼儿CPB合理的灌注管理、预防脑缺血提供理论依据。方法 12只幼猪按照随机表分为3组,对照组、高流量组(H组)、低流量组(L组)。建立单泵双管CPB灌注模型,用血流检测仪直接检测灌注管路流量反映不同流量下脑动脉内血液灌注的变化,并采用近红外分光广度检测技术(near infrared reflectance spectroscopy,NIRS)监测幼猪CPB模型中rSO_2的变化。在CPB开始前10 min、CPB开始后10 min、升主动脉阻断后30 min和升主动脉开放后10 min 4个时间点检测血清S100钙结合蛋白B(S100 B)浓度。分别进行苏木精-伊红(HE)染色、尼氏染色观察海马CA区组织学变化。结果在主动脉阻断期间,H组脑灌注流量[(30.8±9.9)mL/(kg·min)]较L组[(19.0±7.4)mL/(kg·min)]有增高趋势但无统计学差异(P=0.072),且该时间点H组rSO_2值(52.65%±3.1%)显著高于L组(47.3%±3.3%)(P0.05)。海马组织学变化及血清S100 B蛋白水平无组间差异。结论在小型猪体外循环灌注模型中,脑动脉内流量及局部脑氧饱和度监测提示脑血流压力/血流自我调节减弱,高流量组脑灌注效果优于低流量灌注。     

主动脉弓手术停循环与脑灌注期间脑区域氧饱和度监测

目的:明确深低温停循环(DHCA)与脑灌注相结合进行主动脉弓手术期间脑区域氧饱和度监测(rSO2)的价值.方法:28位病人的rSO2被监控,数据被统计分析.结果:DHCA的平均停循环时间是(59±17.1)min,外科手术的结果比较满意,住院期间死亡2例,死亡率(5.6%).虽然全部病人兼有脑灌注支持,rSO2在DHCA期间仍然逐渐下降,平均降到(47±9.7)%,在复温末期又恢复到它的最初水平.有2位病人rSO2降低最明显,在长达83和88min的DHCA之后rSO2分别从57%和56%下降到27%和29%,这2位病人最终发展永久的神经系统损害.我们同时考察了End-rSO2和△-rSO2两个参数,在DHCA期间,脑灌注的灌注流速和这两个参数都存在线性相关.结论:(1)尽管DHCA和一定方式脑灌注的结合能提供大脑更有效的保护,这种保护措施仍然有一个安全的时限;(2)NIRS能实时监控脑rSO2,可用于监测大脑保护是否充分,有利于DHCA下脑灌注参数的凋整.     

血管内支架成形材料在脑供血动脉狭窄治疗中的应用

目的：总结近年来血管内支架成形材料在脑供血动脉狭窄治疗中的应用情况。 方法：由作者应用计算机检索维普数据库中与血管内支架置入治疗脑供血动脉狭窄有关的文章,检索时限2000-01/2010-10。检索关键词：血管内支架成形术;脑供血动脉狭窄;缺血性脑卒中;并发症。纳入标准：血管内支架置入治疗脑供血动脉狭窄的文章。排除标准：重复研究或较陈旧文献。 结果：金属内支架进入临床治疗后取得了令人瞩目的效果,但具有一定的致血栓形成性、永久性存留体内、再狭窄仍较高、金属表面难以附载药物等缺点。针对以上不足,近些年对支架材料、构形设计、制作工艺等均作了不少改进,更引人注目的是20世纪80年代末和90年代初覆膜支架的出现和生物学支架概念的提出,使血管内支架又进入了一个新的阶段。 结论：随着血管内技术的发展,脑保护装置下血管内支架置入已成为治疗颅内外动脉狭窄的主要方法之一,支架技术的安全性和有效性已显著提高,但仍存在如血栓形成、脑出血、再狭窄以及过度灌注等问题。     

脑组织氧分压监测技术的研究与应用进展

脑组织氧分压（brain tissue oxygen partial pressure,PbtiO2) 技术是进入90年代后逐渐成熟起来的脑氧代谢监测方法,与传统的脑氧监测方法相比具有微创,安全,准确的特点,应用这一技术可以对病人进行术中及术后的长期,动态监测,有助于正确判断脑血流量,颅内压,脑灌注压之间的关系,早期判断预后,但脑组织氧分压监测所获得的信息尚需结合其他监测手段获得的数据加以综合分析,才能得出准确结论。     

逆行脑灌注的研究与应用进展

在复杂的心血管手术中,深低温停循环(DHCA)作为重要辅助手段已广泛应用.但DHGA后可产生不同程度的脑损伤,逆行脑灌注(RCP)维持了循环停止中的脑低温,向脑组织提供氧供,清除代谢产物,延长安全时限.但存在灌注条件不易掌握,易引起水肿等缺点.     

脑组织氧分压监测技术的研究与应用进展

脑组织氧分压 (brain tissue oxygen partial pressure,Pbti O2 )技术是进入 90年代后逐渐成熟起来的脑氧代谢监测方法 ,与传统的脑氧监测方法相比具有微创、安全、准确的特点。应用这一技术可以对病人进行术中及术后的长期、动态监测 ,有助于正确判断脑血流量、颅内压、脑灌注压之间的关系 ,早期判断预后。但脑组织氧分压监测所获得的信息尚需结合其他监测手段获得的数据加以综合分析 ,才能得出准确结论     

15例脑动静脉畸形的手术治疗

目的讨论手术切除治疗脑动静脉畸形（AVM）。方法回顾性分析我院自2006年5月～2009年12月间显微手术治疗的15例脑AVM。结果本组术后无死亡病例。术后1天内出现残腔血肿1例,占本组的6.7%,3天内局部脑肿胀2例,占本组的13.3%,以上3例均经加强脱水降颅压、控制血压等治疗而好转。术后患者无再次癫痫发作病例。其余12例（占本组的80.0%）恢复良好,复查DSA均显示脑动静脉畸形已全切除。本组15例随访DSA3年,均无脑动静脉畸形复发病例。结论开颅手术切除是治疗大中型脑AVM的有效手段。在治疗时,应该积极防治正常灌注压突破出血及其他并发症,通过精细的显微手术操作以获得更好的治疗效果。     

亚低温治疗脑卒中及颅脑损伤研究进展

亚低温治疗作为一种脑保护方法已应用在脑卒中和颅脑损伤的治疗中.本文综述了亚低温治疗可能的脑保护机制、亚低温治疗的技术以及在今后的研究与临床应用中需关注的几个关键问题.亚低温治疗的脑保护作用已获得肯定,对亚低温的并发症、实施治疗的时间窗和温度窗、维持低温的时间及复温速率等方面,仍需更进一步的研究和探讨.     

Behaviorally induced changes in length of cerebrum in rats

In normal rats, growth in the width of the cerebral hemispheres ceases about 21 days of age, but growth in length continues at a reduced, steady rate in the young-adult. Three behavioral treatments were used to determine whether this late phase in cerebral growth is sensitive to environmental influences. Rats that were trained on a complex visual discrimination task for 4 months had significantly longer cerebral hemispheres than their passive littermates. Rats that were raised in enriched or social environments had longer cerebral hemispheres than rats raised in isolation. Finally, the cerebrum of unhandled rats was shorter than that of rats handled during infancy; that of the latter was shorter than the cerebrum of trained or enriched animals. No changes were observed under any of these conditions in cerebral width. These results indicate that the length of the cerebrum characteristic of normal rats does not represent a genetically determined, fixed level. This level is not attained under certain rearing conditions and it can be surpassed when the complexity of the environment is increased. The morphological bases of these changes were not determined.     

大鼠脑缺血再灌注损伤IL-8变化的研究

目的：探讨白细胞介素0－8（interleukin-8,IL-8)在脑缺血再灌注损伤中的变化。方法：采用改良Zea Longa线栓法大鼠大脑中动脉闭塞（middle cerebral artery occlusion,MCAO)模型,将大脑中动脉（MCA）先行闭塞2小时,然后进行再灌注不同的时间,应用双抗体夹心间接ELISA法检测实验组和对照组大鼠脑组织及血清中IL－8浓度,结果：缺血2小时再灌注1小时脑组织IL－8含量较低（P＜0．05）,随再灌注时间延长逐渐升高,至22小时达高峰,随后又降低;血清中IL－8含量于再灌注1小时是高,随后缓慢下降,再灌注46小时降至对照组水平;空白组,假手术组脑组织内IL－8含量高于缺血再灌注组（P＜0．01）,结论：IL－8具有双重作用,既参与脑组织的正常代谢及生理功能,又参与了脑缺血再灌注损伤的病理生理过程。     

Modelling the effects of cerebral microvasculature morphology on oxygen transport

The cerebral microvasculature plays a vital role in adequately supplying blood to the brain. Determining the health of the cerebral microvasculature is important during pathological conditions, such as stroke and dementia. Recent studies have shown the complex relationship between cerebral metabolic rate and transit time distribution, the transit times of all the possible pathways available dependent on network topology. In this paper, we extend a recently developed technique to solve for residue function, the amount of tracer left in the vasculature at any time, and transit time distribution in an existing model of the cerebral microvasculature to calculate cerebral metabolism. We present the mathematical theory needed to solve for oxygen concentration followed by results of the simulations. It is found that oxygen extraction fraction, the fraction of oxygen removed from the blood in the capillary network by the tissue, and cerebral metabolic rate are dependent on both mean and heterogeneity of the transit time distribution. For changes in cerebral blood flow, a positive correlation can be observed between mean transit time and oxygen extraction fraction, and a negative correlation between mean transit time and metabolic rate of oxygen. A negative correlation can also be observed between transit time heterogeneity and the metabolic rate of oxygen for a constant cerebral blood flow. A sensitivity analysis on the mean and heterogeneity of the transit time distribution was able to quantify their respective contributions to oxygen extraction fraction and metabolic rate of oxygen. Mean transit time has a greater contribution than the heterogeneity for oxygen extraction fraction. This is found to be opposite for metabolic rate of oxygen. These results provide information on the role of the cerebral microvasculature and its effects on flow and metabolism. They thus open up the possibility of obtaining additional valuable clinical information for diagnosing and treating cerebrovascular diseases.     

颅内出血动态过程的电阻抗成像仿真研究

基于等位线反投影算法的动态电阻抗断层成像技术具有对目标定位准确，成像速度快，有一定的分辨率等优点。将该技术应用于颅内出血疾病的实时监测，及时反映颅内出血的变化情况，这在医学上有着重要意义。作为该技术应用于颅内出血实时监测的基础研究，本研究利用等位线反投影算法，仿真了动态电阻抗断层成像技术应用于颅内出血疾病实时监测过程。研究结果表明，动态电阻抗断层成像等位线反投影算法重建的图像可以反映颅内出血的变化情况，能够应用于颅内出血动态过程监护。     

Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48?h of reperfusion. The effects of rapamycin (250?μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood–brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.     

复合环境因素诱导大鼠脑卒中机体防御基因表达的改变及意义

目的：探讨环境因素对脑卒中发生、发展的影响。方法：应用冷刺激加高盐饮食复合环境因素作用于Wistar大鼠，诱发大鼠高血压脑卒中作为模型，应用新近发展起来的抑制性消减杂交技术对卒中鼠和正常对照鼠脑的差异基因进行筛选。经过两轮杂交后，每组随机挑取288个克隆，进行测序及GenBank BLAST生物信息分析。结果：两组共有456个可用序列，我们对每个与已知基因高度同源的序列以功能为参照进行了分类，发现脑卒中时细胞与机体防御基因表达明显下调（P＜0．01），而与代谢相关基因（43个克隆与线粒体基因高度同源，P＜0．01）表达明显上调。结论：脑卒中时与应激相关的基因表达下调，说明机体的防御能力减弱。     

Background suppression in arterial spin labeling MRI with a separate neck labeling coil

In arterial spin labeling (ASL) MRI to measure cerebral blood flow (CBF), pair-wise subtraction of temporally adjacent non-labeled and labeled images often can not completely cancel the background static tissue signal because of temporally fluctuating physiological noise. While background suppression (BS) by inversion nulling improves CBF temporal stability, imperfect pulses compromise CBF contrast. Conventional BS techniques may not be applicable in small animals because the arterial transit time is short. This study presents a novel approach of BS to overcome these drawbacks using a separate 'neck' radiofrequency coil for ASL and a 'brain' radiofrequency coil for BS with the inversion pulse placed before spin labeling. The use of a separate 'neck' coil for ASL should also improve ASL contrast. This approach is referred to as the inversion-recovery BS with the two-coil continuous ASL (IR-cASL) technique. The temporal and spatial contrast-to-noise characteristics of basal CBF and CBF-based fMRI of hypercapnia and forepaw stimulation in rats at 7 Tesla were analyzed. IR-cASL yielded two times better temporal stability and 2.0-2.3 times higher functional contrast-to-noise ratios for hypercapnia and forepaw stimulation compared with cASL without BS in the same animals. The Bloch equations were modified to provide accurate CBF quantification at different levels of BS and for multislice acquisition where different slices have different degree of BS and residual degree of labeling. Improved basal CBF and CBF-based fMRI sensitivity should lead to more accurate CBF quantification and should prove useful for imaging low CBF conditions such as in white matter and stroke.     

MRI of stroke using hyperpolarized 129Xe

Because there is no background signal from xenon in biological tissue, and because inhaled xenon is delivered to the brain by blood flow, we would expect a perfusion deficit, such as is seen in stroke, to reduce the xenon concentration in the region of the deficit. Thermal polarization yields negligible xenon signal relative to hyperpolarized xenon; therefore, hyperpolarized xenon can be used as a tracer of cerebral blood flow. Using a rat permanent right middle cerebral artery occlusion model, we demonstrated that hyperpolarized ¹²⁹Xe MRI is able to detect, in vivo, the hypoperfused area of focal cerebral ischemia, that is the ischemic core area of stroke. To the best of our knowledge, this is the first time that hyperpolarized ¹²⁹Xe MRI has been used to explore normal and abnormal cerebral perfusion. Our study shows a novel application of hyperpolarized ¹²⁹Xe MRI for imaging stroke, and further demonstrates its capacity to serve as a complementary tool to proton MRI for the study of the pathophysiology during brain hypoperfusion. Copyright © 2010 John Wiley & Sons, Ltd.     

线粒体基因表达改变在大鼠脑卒中发生中的作用

目的　探讨线粒体基因表达改变在大鼠脑卒中发生中的作用。方法　应用冷刺激加高盐饮食复合环境因素作用于 Wistar大鼠 ,诱发大鼠高血压脑卒中 ,应用抑制性差减杂交技术对卒中样发作鼠和正常对照鼠脑的差异基因进行筛选。经过两轮杂交后 ,产生的克隆均为脑卒中鼠脑组织特异表达的序列。每组随机挑取 2 88个克隆 ,进行测序及 Gen Bank Blast生物信息分析。结果　两组共有 4 5 6个可用序列 ,我们对每个与已知基因高度同源的序列以功能为参照进行了分类 ,发现大鼠脑卒中后脑组织线粒体基因转录出现的频数高达 2 6 .5 % ,6 0个克隆与线粒体基因高度同源 (P<0 .0 1) ,线粒体基因表达明显上调。结论线粒体基因表达发生改变 ,可能造成脑卒中的敏感性增加。     

经外侧裂入路行基底节区高血压脑出血手术的解剖和技巧

目的:为经外侧裂行基底节区高血压手术提供显微外科解剖学基础和手术技巧。方法:15例头颅湿标本,模拟手术入路观察外侧裂区解剖结构和相互毗邻关系并进行手术入路研究。结果:视辐射分前、中、后3束,前束覆盖颞角前尖端顶壁和侧壁,中束在颞角上壁和侧壁,前束和后束从外侧膝状体发出后向前卷曲,而后束离开外侧膝状体后终止于距状沟上岸没有向前的卷曲,后束走行于侧脑室下角的外侧壁,这样视辐射纤维存在于脑侧面的颞角的顶壁和中后及侧壁,颞角下壁没有视辐射纤维;经外侧裂、梨状皮质和钩的入路行基底节区高血压手术时,可以不损伤视辐射和钩束。结论:手术入路经外侧裂通过钩前面和上面的梨状皮质能安全进入基底节区而不损伤视辐射和钩束的主要部分。