实验性高血压对脑血流自动调节功能影响的动态观察

目的　动态观察高血压对脑血流自动调节下限的影响 ,及其与脑血管病理形态改变的关系。方法　选用 80只易卒中型肾血管性高血压大鼠 (RHRSP) ,在术后不同的时间点 ,利用临界关闭压测定脑血流自动调节下限 (LLCA) ,并动脉插管测定血压和定量分析脑血管的形态变化 ,分别与正常血压对照组 (80只 )的结果进行比较。结果　RHRSP组的LLCA术后第 6周开始升高 ,第 10周后明显高于对照组 (P <0 0 5 ) ,基本稳定于 110mmHg左右。多元回归分析发现 ,LLCA的升高主要与平均动脉压呈正相关 (r=0 96 8,P <0 0 5 ) ,与脑内微动脉的中膜厚度呈正相关 (r=0 94 0 ,P <0 0 5 )。并且LLCA的变化在平均动脉压改变的中间过程最明显 ,而于平均动脉压轻度和重度升高时变化不大 ,呈“S”形改变 (R2 =0 970 1,P <0 0 5 )。结论　高血压LLCA上移主要与平均动脉压有关 ,是脑内微动脉中膜增厚的体现 ,于血压升高中期改变最为明显。     

癫痫患者动态脑血流自动调节功能研究

目的 探究癫痫患者的dCA功能。 方法 研究纳入100例癫痫患者和100例年龄、性别相匹配的健康志愿者作为对照组，分别测定其 dCA功能。采用TCD联合无创指尖血压监测法分别连续采集受试者双侧MCA脑血流速度（cerebral blood flow velocity，CBFV）和动脉血压（arterial blood pressure，ABP）信号。将采集的CBFV和ABP信号经 过传递函数法（transfer function analysis，TFA）分析，得出dCA参数（相位差和增益）。 结果 癫痫患者的总体相位差显著低于正常对照组（P =0.046），提示其dCA功能受损。此外，合并 发作间期慢波的患者其相位差更低（P =0.012），dCA功能受损更明显。EEG表现为局灶性放电的患者 与表现为多灶性放电的患者的相位差无显著性差异。同样，在EEG表现为单侧放电的患者中，其放电 侧大脑半球与放电对侧大脑半球的相位差也无显著性差异。通过单因素和多因素回归模型分析临床 因素与dCA参数的关系，发现发作间期慢波与相位差受损独立相关（P =0.016）。 结论 癫痫患者的dCA功能受损，而痫样放电合并发作间期慢波患者dCA受损更明显。dCA功能与癫 痫患者的放电类型、放电部位无关。发作间期慢波是癫痫患者dCA功能受损的独立预测因素。 临床研究注册号 NCT02775682     

糖尿病脑梗塞患者脑血流自动调节功能的改变

糖尿病脑梗塞患者脑血流自动调节功能的改变夏惠治刘定华惠黎王立我们从１９９３～１９９５年观察了３２例糖尿病脑梗塞患者脑血流自动调节功能的改变，现报告如下。资料和方法一、一般资料：本组男１８例，女１４例。年龄３５岁～８６岁，平均６０．７岁。全部病例均符合...     

脑血流自动调节的研究进展

脑血流自动调节（ＡＣＢＦ）是机体在应急情况下的代偿反应,脑血流量（ＣＢＦ）的恒定保证了脑组织功能的完整和意识清醒。ＡＣＢＦ研究为脑灌注压改变时的临床处理提供了理论依据。作者对ＡＣＢＦ的近年研究进展作一介绍。１概念机体为保证正常的生理功能必须保持ＣＢＦ...     

脑血流自动调节及其在精神科的研究进展

本介绍脑血流自动调节的概念，机制，障碍及抗精神病药对它的影响。     

脑梗死急性期患者脑血流自动调节功能观察

目的 利用临界关闭压（critical closing pressure,CCP）探讨脑梗死急性期自动调节功能及与病情的相关性。      

鼠脑缺血后软脑膜微循环变化的实验研究——闭合骨窗动物模型的制作

本文是利用闭合式颅骨开窗技术制成脑微循环小室观察双侧颈总动脉阻塞前后大鼠软脑膜微循环变化及探讨有关发生机理的系列研究的一部分。详细描述了大鼠闭合式颅骨开窗的具体做法及注意事项,介绍了颅骨开窗技术的发展过程。在当前人们尚无法直接观察到脑实质内血管变化的情况下,可以通过闭合式颅骨骨窗直接观察软脑膜微血管的改变,从而推测脑内血管的变化。     

传递函数分析动态脑血流自动调节：源于国际脑血流自动调节研究网络的白皮书

脑血流自动调节（cerebral autoregulation,CA）是血压变化时大脑维持足够脑灌注的内在能力。过去的30年,研究者已经提出了诸多分析CA的方法,但至今无公认的金标准,采用什么方法定量CA仍是个人主观的选择。尽管如此,由于CA的概念代表了血压（刺激或者输入信号）与脑血流（反应或者输出信号）之间的动态关系,故目前最通用的研究血压自发波动的分析方法是传递函数分析。虽然理论上可行,但是文献显示,传递函数分析方法在实践中存在相当大的主观性,这限制了研究之间的比较,也阻碍了其临床应用。因此,本白皮书旨在规范化研究动态CA的传递函数分析方法的参数及设置,建立标准,以利于其临床应用,该推荐的研发始于（但不限于）脑血流自动调节研究网络（CARNet-www.car-net.org）。     

易卒中型肾血管性高血压大鼠的脑血流自动调节下限与最低耐受压

目的　研究易卒中型肾血管性高血压大鼠 (RHRSP)的脑血流 (CBF)自动调节下限及其最低耐受压。　　方法　用氢清除法测定RHRSP和正常SD大鼠在不同低血压水平时 ,一侧顶枕交界区皮质和海马的局部CBF(rCBF) ;72小时后计算RHRSP和SD大鼠海马CA1 区神经细胞 (CA1 NC)线粒体的体密度 (Vv)、比表面 (δ)、平均体积 ( V)和数密度 (Nv) ,　　 结果　正常SD大鼠在平均动脉压 (MABP)为 1 0 67kPa、9 3 3kPa和 8kPa时 ,rCBF值无显著减少。在MABP为 1 0 67kPa时 ,RHRSP的rCBF值显著减少 ;超微结构观察发现CA1 NC无明显缺血改变 ,当MABP为 9 3 3kPa时 ,CA1 NC缺血明显 ;细胞形态分析发现 9 3 3kPa组与 1 0 67kPa组比较 ,前者线粒体的Vv和 V显著增大 ,δ和Nv显著减小。　　结论　RHRSP的CBF自动调节下限上移至 1 0 67kPa,并与其最低耐受压十分接近 ,表明RHRSP是一种研究高血压脑血管损害较理想的动物模型     

The course of dynamic cerebral autoregulation during cervical internal carotid artery occlusion

Abstract

Objectives: The selection of patients with cervical internal carotid artery occlusion (ICAO) for extracranial-intracranial bypass surgery is based on exhausted cerebrovascular reactivity to vasodilatory stimuli. However, a spontaneous increase in this reactivity can occur with time, questioning the ideal time for bypass surgery. In contrast, the natural course of dynamic cerebral autoregulation is not known in these patients.

Methods: Patients with cervical ICAO were examined at baseline and after a mean interval of 15 months. Dynamic autoregulation was determined by transcranial Doppler sonography in both middle cerebral arteries via respiratory-induced 0·1-Hz oscillations (phase, available for n=47 patients) and correlation analysis between diastolic blood pressure and Doppler signal (index Dx, n=55 patients). Pre-defined cut-off values and repeatability measures of healthy controls were used to define significant individual changes in autoregulation.

Results: Group mean comparisons between studies were not significant for any autoregulation parameter. The intraclass correlation coefficient between studies was high for phase (ipsilateral: 0·83; contralateral: 0·74), and moderate for Dx (ipsilateral: 0·63; contralateral: 0·35). There was no clear trend for an improvement across cut-off values. A significant individual improvement/deterioration in autoregulation occurred in 6%/6% for phase and 13%/9% for Dx.

Discussion: Dynamic autoregulation only rarely improves during the course of ICAO. This finding should be considered when deciding for or against a policy of delaying extracranial-intracranial bypass surgery for reasons of a potentially improving hemodynamic status.     

Microvascular structure after embolic focal cerebral ischemia in the rat

OBJECTIVES: We analyze morphological alterations of cerebral neovascularization after stroke using a new 3D imaging software program. METHODS: Male Wistar rats underwent unilateral embolic middle cerebral artery occlusion (MCAo) by a single fibrin rich clot. Subjects were sacrificed from 1 to 28 days post infarct. Vessel perimeters were measured on coronal sections stained with endothelial cell-specific antibody to von Willebrand's factor. Vessel segment lengths, diameters and number of vessels were analyzed on cerebral microvessels perfused with FITC-dextran 14 days after ischemia using LSCM and a 3-D vessel quantification program. RESULTS: The mean number of microvessels with enlarged perimeters significantly increased in the ipsilateral cortex at day 7 when compared to the contralateral cortex (29.7+/-14.7 vs. 3.7+/-2.5, P<0.05). Subsequently, differences in the number of microvessels with enlarged perimeters decreased on days 14 and 28. Fourteen days post-MCA occlusion, microvessel segment length (15.0 vs. 26.0 microm, P<0.05) and diameter (3.14 vs. 3.75 microm, P<0.05) significantly decreased in the ipsilateral hemisphere when compared to the contralateral hemisphere, respectively. Furthermore, the mean total number of these smaller microvessels increased in the ipsilateral hemisphere (57.33+/-14.5 vs. 32.22+/-11.7, P<0.05). CONCLUSIONS: Focal cerebral ischemia induces morphological changes (early dilated microvessels followed by decreased microvessel segment length and diameter) that are consistent with newly generated microvessels.     

Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats

Progesterone (PROG) is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous PROG has been shown to reduce secondary neuronal loss in conjunction with attenuated brain edema after cerebral contusion and to reduce brain edema after focal cerebral ischemia. In the present study, we assessed the neuroprotective potential of PROG in a model of focal cerebral ischemia in the rat. Forty-eight male Wistar rats were randomly assigned to 4 groups, i.e. pretreatment with water soluble PROG, or dimethyl sulfoxide (DMSO) dissolved PROG, or DMSO as control or delayed treatment with DMSO dissolved PROG. Middle cerebral artery occlusion (MCAO) was induced by insertion of an intraluminal suture and reperfusion was performed by withdrawing the suture. Pretreatments were initiated 30 min before MCAO via intraperitoneal injection. Delayed treatment was initiated upon reperfusion following 2 h of MCAO. Infarct volume, body weight loss, and neurological deficit were measured 48 h after MCAO. Pre- and delayed treatment with DMSO dissolved PROG resulted in a 39% (P < 0.05) and 34% (P < 0.05) reduction in cerebral infarction, respectively, along with decreased body weight loss and improved neurological function as compared to control animals, whereas no statistically significant reduction in infarct volume by water soluble PROG was found. We demonstrated that administration of PROG to the male rat before or 2 hours after onset of MCAO reduces ischemic cell damage and improves physiological and neurological function 2 days after stroke. These results suggests potential therapeutic properties of PROG in the management of stroke.     

Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases

Chronic cerebral hypoperfusion has been associated with cognitive decline in aging and Alzheimer's disease. Moreover, the pattern of cerebral blood flow in mild cognitive impairment has emerged as a predictive marker for the progression into Alzheimer's disease. The reconstruction of a pathological condition in animal models is a suitable approach to the unraveling of causal relationships. For this reason, permanent, bilateral occlusion of the common carotid arteries (2VO) in rats has been established as a procedure to investigate the effects of chronic cerebral hypoperfusion on cognitive dysfunction and neurodegenerative processes. Over the years, the 2VO model has generated a large amount of data, revealing the 2VO-related pattern of cerebral hypoperfusion and metabolic changes, learning and memory disturbances, failure of neuronal signaling, and the neuropathological changes in the hippocampus. In addition, the model has been introduced in research into ischemic white matter injury and ischemic eye disease. The present survey sets out to provide a comprehensive summary of the achievements made with the 2VO model, and a critical evaluation and integration of the various results, and to relate the experimental data to human diseases. The data that have accumulated from use of the 2VO model in the rat permit an understanding of the causative role played by cerebral hypoperfusion in neurodegenerative diseases. Thorough characterization of the model suggests that 2VO in the rat is suitable for the development of potentially neuroprotective strategies in neurodegenerative diseases.     

The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion

Summary The behavior of the blood-brain barrier (BBB) was studied in cats following release after 1-h middle cerebral artery (MCA) occlusion. The regional cerebral blood flow (rCBF) was determined by hydrogen clearance method in the caudate nucleus and the cerebral cortex. The BBB was assayed with Evans blue (EB) tracer and by immunohistochemical peroxidaseantiperoxidase (PAP) method. Following release of MCA occlusion, there were two openings of the BBB, separated by a refractory period. The first opening, occurred shortly after recirculation; this was associated with rCBF below 15 ml/100 g/min during the ischemic period and a pronounced reactive hyperemia promptly following release of MCA occlusion. A refractory period of the BBB was indicated by the absence of EB leakage in cats injected with the tracer 30 min before killing at 3 h after recirculation, although the rCBF values in these animals were even lower (6±1 ml/100 g/min) during occlusion, and all of them showed a pronounced hyperemia after recirculation. The occurrence of the previous BBB opening in these animals was confirmed by the PAP staining. The second opening of the BBB was observed at 5 and 72 h after recirculation in cats which were injected with EB 30 min before killing, and which showed rCBF below 15 ml/100 g/min during occlusion, followed by a pronounced reactive hyperemia. No EB extravasations were observed at any time in cats in which the rCBF during occlusion was above 15 ml/100 g/min and which failed to show a marked reactive hyperemia.     

Evaluation of cerebral autoregulation following diffuse brain injury in rats

Abstract

The normal cerebral circulation has the ability to maintain a stable cerebral blood flow over a wide range of cerebral perfusion p(essures and this is known as cerebral autoregulation. This autoregulation may be impaired in the injured brain. Closed head injury was induced in 28 Sprague-Dawley rats weighing 400-450 g. Four groups were studied: control group, head injured rat from meter height using 350 g, 400 g and 450 g respectively. CBF, volume velocity was monitored using laser-Doppler flowmetry together with monitoring of ICP and arterial blood pressure. Correlation to assess the relationship between CBF and CPP was done in each animal every hour. If correlation coefficient was> 0.85 and CPP was within normal range, loss of autoregulation was hypothesized. Chi square test, ANOVA test and unpaired Studen(s t-test were done and significant level of p < 0.05 was established. Mean CBF in injured rats was significantly lower than controls (p = 0.028) at the fifth hour. CBV was lower in the group of 450 g 1 m impact than in controls at 3 h (p = 0.04). Velocity in the group ofall injured rats, was significantly lower than in controls at 3 h (p = 0.032) and at 4 h (p = 0.027). Loss ofautoregulation was seen during first four hours after trauma in all groups of rats who sustained injury. Statistical significant difference (p = 0.041) in loss of autoregulation between injured and control animals was seen. No loss of autoregulation was observed in the control group. In conclusion CBF and CPP provide information about loss of autoregulation in diffuse brain injury. Decrease in CBF and increase of ICP is observed as a result ofloss of cerebral autoregulation. Knowledge of loss of autoregulation could give important information and help in the management of head injured patients. [Neural Res 1997; 19: 393-402]     

A change of P-selectin immunoreactivity in rat brain after transient and permanent middle cerebral artery occlusion

Abstract

Although the role of an adhesion molecule such as P-selectin may be important in the pathogenesis of stroke, temporal, spacial, and cellular profiles of the expression ofsuch a protein has not been fully studied in the case ofthe middle cerebral artery (MCA) occlusion and reperfusion in rat brain. Change in expression of immunoreactive P-selectin was examined in rat brain after transient MCA occlusion (MCAO) in comparison to that of permanent occlusion with an anti-P-selectin monoclonal antibody. Western blot analyses were performed to ensure the selective detection of immunoreactive P-selectin protein with the monoclonal antibody using brain homogenates before and after MCAO. Temporal, spacial, and cellular changes of P-selectin expressions were evaluated with rat brain sections at 2, 8 h, 1 and 3 days of permanent MCAO, and at 2, 8 h, 1, 3 and 7 days of reperfusion after 1 h of transient MCAO. Western blot showed a single band with a molecular weight of 140 kOa for both cases with permanent occlusion and reperfusion. P-selectin immunoreactivity was not normally present in rat brain sections. However, it was expressed mainly in the post-capillary venules of the cerebral cortex and caudate in the MCA territory with a peak at 2-8 h after permanent occlusion and at 8 h to 1 day after the reperfusion. The expression was diminished by 1 day ofpermanent occlusion and 3 days of reperfusion. The maximum staining in the case of permanent MCAO was stronger than the case with reperfusion. However, spacial distribution of the staining was similar in the cerebral cortex and caudate between the cases with permanent or transient MCAO. These results suggest a different temporal but similar spacial and cellular expression of P-selectin immunoreactivity between permanent occlusion and reperfusion of MCA in rat brain. [Neural Res 1998; 20: 463–469]     

氟美松对成年大鼠持续性局灶性脑缺血后凋亡和Bcl-2蛋白表达的影响

目的研究药理剂量氟美松对成年大鼠持续性局灶脑缺血后凋亡及凋亡相关基因Bcl-2表达的影响.方法健康成年雄性SD大鼠随机分为假手术组、生理盐水组、氟美松组, 分别对应脑缺血3 h、 6 h、 12 h、 24 h、 48 h、 72 h、 120 h等时间点;行左侧大脑中动脉近端电凝术建立持续性局灶脑缺血模型;术后1 h生理盐水组静脉注射生理盐水, 氟美松组静脉注射氟美松(0.5 mg*kg-1*d-1);行常规HE染色, 原位末端TUNEL法标记凋亡细胞, 免疫组织化学法检测Bcl-2蛋白表达.结果持续性局灶脑缺血后细胞凋亡、 Bcl-2蛋白表达主要分布在梗死灶的边缘区域, 脑缺血2 d出现细胞凋亡并持续到缺血5 d;氟美松组细胞凋亡出现时间提前到缺血1 d, 而且缺血2 d、 5 d凋亡细胞数量较生理盐水组增加;脑缺血3 h～5 h梗死灶边缘区域都有Bcl-2蛋白表达;氟美松处理组6 h～5 d Bcl-2蛋白表达细胞密度明显低于生理盐水组.结论持续性局灶脑缺血早期给予氟美松可促进梗死灶边缘区的细胞凋亡, 引作用与其下调Bcl-2的基因表达有关.     

双侧肾上腺切除大鼠脑缺血后血脑屏障破坏的研究

目的观察脑缺血时体内自身的糖皮质激素变化对血脑屏障（ＢＢＢ）的影响。方法采用线栓法造成脑缺血模型,用辣根过氧化物酶组织化学染色的方法,观察双侧肾上腺切除大鼠局灶脑缺血后血脑屏障的改变。结果双侧肾上腺切除后脑缺血组（Ａ组）大鼠ＢＢＢ破坏的范围为１０．１０１±１．４１１ｍｍ２;单纯脑缺血组（Ｂ组）大鼠ＢＢＢ破坏范围为６．１９１±１．０４５ｍｍ２,Ａ组大鼠ＢＢＢ破坏的范围大于Ｂ组大鼠ＢＢＢ破坏的范围（Ｐ＜０．０１）。结论脑缺血时体内自身的糖皮质激素升高对ＢＢＢ具有保护作用。