兔脑缺血再灌注后尼莫地平对脑微循环影响的实验研究

在夹闭双侧颈总动脉和椎动脉造成严重脑缺血２０分钟的基础上，应用微循环闭路电视显微系统行颅骨开窗法对兔脑软脑膜微循环录像，直接动态观察钙拮抗剂尼莫地平对脑复苏后微循环的影响。再灌注期，尼莫地平能显著地扩张微动脉，并持续１００分钟以上，明显地延缓延迟性低灌注时相。结果提示：尼莫地平具有不同程度地改善脑缺血后微循环异常，增加脑组织血液供给，减轻再灌注损伤。     

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。     

20%甘露醇对颅脑伤后脑微循环影响的实验研究

目的 研究猫低速弹颅脑伤(LMCW)后脑微循环的改变以及20％甘露醇对脑微循环障碍的影响。方法 改良Carey法制作猫LMCW模型，将12只猫分为单纯创伤组(C组)和甘露醇治疗组(Man组)。微循环显微镜活体实时观察软脑膜微循环并测量软脑膜细动脉(Da)、细静脉(Dv)管径；测量微区CBF；监测生命体征：采血测算重要血液流变学指标，8h后观察创伤对侧组织病理学变化。结果 猫低速弹颅脑伤后Da、Dv收缩持续30min，之后C组微血管扩张至2h时恢复正常，5～8hDa痉挛，Dv扩张、瘀血；各血液流变学指标均明显异常，至8h仍未恢复。结论 20％甘露醇通过改善血液的流变学特性，减轻了颅脑伤后的脑微循环障碍和病理损害。     

抑郁症患者脑血流速度的研究

运用经颅多普勒超声器测定２２例抑郁症患者脑及颈动脉的血流速度，并与健康正常人进行对照，发现抑郁症患者双侧颈总动脉及颈内动脉血流速度明显减慢，供应给脑部的血流减少；右侧大脑中动脉吸大脑后动脉血流速度偿性加快，脑及颈动脉血流速度的改变与Ｈａｍｉｌｔｏｎ抑郁量表总分无明显相关，提示抑郁症患者大脑半球左侧供血障碍更加明显，但脑血流测量的结果并不能反映疾病的严重程度，仅为抑郁症病因研究提供了有益的线索。     

烟雾病的外科治疗进展

<正>烟雾病(Moyamoya disease,MMD)是一种原因不明的慢性进行性脑血管闭塞性疾病。其主要表现为单侧或双侧颈内动脉远端、大脑中动脉和大脑前动脉近端狭窄或闭塞伴脑底部和软脑膜烟雾状、细小血管形成[1]烟雾病的治疗可分为药物治疗和手术治疗两类。药物治疗至今尚无根治性治疗方法,内科保守治疗给予血管扩张剂、抗血小板聚集药物、类固醇激素类、改善微循环药物及神经营养剂等进行对症治疗,效果欠佳[2]。手术治疗主要原理是借助颈外动脉系统来     

鼠大脑中动脉阻断后软脑膜微血管的动态变化

目的　观察大鼠一侧大脑中动脉阻断后同侧软脑膜小动脉和小静脉管径的变化 ,并探讨其发生的可能机制。方法　 ( 1)采用穿线法阻断大鼠一侧大脑中动脉 ,制作脑缺血模型 ;( 2 )制备一 2 5mm2 的颅窗 ;( 3 )测定大鼠大脑中动脉阻断后 5、10、 15、 2 0、 3 0、 40、 5 0min及 60min时软脑膜小动脉和小静脉管径 ;( 4 )实验数据以 ( x±s)表示 ,用t检验比较均数间的差异 ,P <0 0 5 ,有显著性差异。结果　大鼠一侧大脑中动脉阻断后 ,同侧软脑膜小动脉和小静脉管径发生变化 ,表现为小动脉和小静脉在 5min时即开始逐渐扩张 ,3 0min时达高峰 ,以后逐渐收缩 ,至 60min时其管径仍比大脑中动脉未阻断者的管径大。结论　当大鼠一侧大脑中动脉阻断后 ,这一动脉供血区微血管先扩张后收缩 ,与脑微循环障碍、O2 及葡萄糖下降有关。推测这一变化是由于缺血区乳酸增加和PH值下降     

大脑中动脉阻断大鼠软脑膜微血管的早期变化

目的 :观察大脑中动脉阻断大鼠软脑膜小动脉和小静脉管径的动态变化 ,并探讨其发生机制。方法 :采用穿线法阻断大鼠一侧大脑中动脉复制大鼠脑缺血模型 ;制备颅窗 ,应用微循环显微镜及其图像分析系统观察大鼠同侧软脑膜小动脉和小静脉管径(AD、VD)的动态变化。结果 :大脑中动脉阻断大鼠同侧软脑膜小动脉和小静脉逐渐扩张 ,3 0min时达高峰 ,与阻断前相比管径有显著性差异 ,以后又逐渐收缩 ,1h时仍比阻断前的管径大。结论 :局灶性脑缺血后脑微循环发生动态变化 ,其发生机制可能是因微血管内皮细胞因缺血性损伤异常分泌和释放血管活性物质调节血管张力     

大脑中动脉阻断大鼠软脑膜微血管的早期变化

目的：观察大脑中动脉阻断大鼠软脑膜小动脉和小静脉管径的动态变化，并探讨其发生机制。方法：采用穿线法阻断大鼠一侧大脑中动脉复制大鼠脑缺血模型；制备颅窗，应用微循环显微镜及其图像分析系统观察大鼠同侧软脑膜小动脉和小静脉管径（AD、VD）的动态变化。结果：大脑中动脉阻断大鼠同侧软脑膜小动脉和小静脉逐渐扩张，30min时达高峰，与阻断前相比管径有显著性差异，以后又逐渐收缩，1h时仍比阻断前的管径大。结论：局灶性脑缺血后脑微循环发生动态变化，其发生机制可能是因微血管内皮细胞因缺血性损伤异常分泌和释放血管活性物质调节血管张力。     

环指蛋白213基因突变导致的烟雾病一家系

烟雾病(Moyamoya disease)又称脑底异常血管网病,是以双侧颈内动脉虹吸部及大脑前、大脑中动脉起始部管腔进行性狭窄或闭塞,并伴有颅底软脑膜动脉、穿通动脉等小血管代偿性增生或扩张,形成脑底异常血管网为特征的一种少见的慢性脑血管闭塞性疾病,在影像学上多有侧支循环的表现[1].目前有关烟雾病的病因及发病机制还不清楚,但有证据表明,遗传因素在烟雾病发病过程中起到了重要作用.烟雾病患者中的10％ ～ 15％具有家族史,同卵双胞胎的患病率高达80％[2].     

精神分裂症患者脑血流速度的对照研究

目的了解精神分裂症患者脑血流速度的情况。方法运用多普勒超声仪测定６０例精神分裂症患者脑及颈动脉的血流速度，并与４０例健康正常人对照比较。结果发现精神分裂症患者双侧颈总动脉及右侧颈内动脉血流速度明显减慢，流向脑部的血液明显减少。左侧椎动脉、左侧大脑前及两侧小脑后下动脉的血流速度明显减慢。结论精神分裂症患者脑内局部血液供应减少。     

Quantitative measurement of blood flow velocity in feline pial arteries during hemorrhagic hypotension and hypercapnia

Due to methodologic difficulties, few investigations have been made on the blood flow velocity in the cerebral microcirculation. Using a newly developed video camera method, we simultaneously measured the blood flow velocity and diameter of pial arteries during hemorrhagic hypotension, after blood pressure recovery, and during CO2 inhalation in cats. When the mean arterial blood pressure was lowered from 129.7 +/- 6.6 to 71.5 +/- 4.1 mm Hg, the blood flow velocity inevitably decreased from 36.6 +/- 5.3 to 27.0 +/- 3.9 mm/sec (p less than 0.001). The calculated blood flow rate [pi X (diameter/2)2 X flow velocity] was preserved in cases with concomitant vasodilation. Conversely, the blood flow velocity increased from 25.3 +/- 5.1 to 31.0 +/- 5.4 mm/sec (p less than 0.001) after mean arterial blood pressure recovery from 67.1 +/- 3.7 to 129.8 +/- 5.8 mm Hg. The blood flow rate was again preserved in vessels with a vasoconstrictive response. Each pial artery apparently dilated or constricted in proportion to the decrease or increase in flow velocity during blood pressure changes, maintaining a constant cerebral blood flow. This indicated the importance of the pial arteries in the mechanisms of cerebral blood flow autoregulation. During 5% CO2 inhalation, the blood flow velocity increased markedly from 25.4 +/- 4.6 to 37.2 +/- 10.0 mm/sec (p less than 0.05), while the pial artery diameter (85.0 +/- 13.7 microns) increased by 9.6 +/- 1.5% (p less than 0.01). The increased flow velocity might be attributable to preferential dilatation of small arterioles or intraparenchymal vessels during hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets

Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets.     

Reactivity of rat pial arterioles and venules to adenosine and carbon dioxide: with detailed description of the closed cranial window technique in rats

This study describes a closed cranial window technique that allows the observation and measurement of rat pial arterioles and venules in situ. The resolving power of this system is 1-2 microns. Using this sensitive technique, we characterized the responses to 7% carbon dioxide inhalation and adenosine in arterioles (10-70 microns) and venules (15-100 microns). During carbon dioxide inhalation, larger arterioles (greater than 40 microns) dilated more than smaller arterioles (less than 20 microns). There was limited vasoreactivity of pial venules during CO2 inhalation. Dilation of arterioles was initially observed with an adenosine concentration of 10(-8) M. Almost a twofold increase in diameter was noted at 10(-3) M. In contrast to the effect of CO2 inhalation, the degree of dilation with topical application of adenosine was not size dependent. Pial venules did not respond to adenosine. The technique for observation of pial vessels using the closed cranial window and for measurement of vessel diameter by video camera system microscopy is a powerful tool for studying in vivo the cerebral circulation in the rat.     

The effects of cerebral ischemia on the rat choroid plexus.

Although the blood-brain barrier effects of cerebral ischemia have been extensively examined, less attention has focused on ischemia-induced damage to the choroid plexuses that form the blood-cerebrospinal fluid (CSF) barrier (BSCFB). This study examined the rat lateral ventricle choroid plexuses (LVCP) in three ischemic models, bilateral common carotid artery occlusion (2VO)+hypotension with or without reperfusion and permanent middle cerebral artery (MCA) occlusion with or without a tandem common carotid artery occlusion. Blood flow was assessed using [(14)C]-N-isopropyl-p-iodoamphetamine, and LVCP injury by tissue edema, alterations in [(14)C]glutamine transport and BSCFB disruption (measured with [(3)H]inulin). 2VO+hypotension caused an 87% reduction in LVCP blood flow (P<0.01) and a progressive reduction in LVCP glutamine transport. In contrast to cortex, there was no LVCP hyperemia or delayed hypoperfusion on reperfusion, but there was marked BSCFB disruption. After 30 mins of 2VO+hypotension with 6 h of reperfusion, the [(3)H]inulin entry into CSF was increased threefold (P<0.05). Blood-CSF barrier rather than blood-brain barrier disruption appeared to be the main cause of enhanced [(3)H]inulin entry into hippocampus. Middle cerebral artery occlusion with and without a tandem common carotid artery occlusion only caused 53% and 38% reductions in LVCP blood flow but induced LVCP edema. Results suggest that the LVCP is selectively vulnerable to ischemic injury in terms of the absolute blood flows or, for the MCA occlusion models, the % reductions in flows required to induce injury. BCSFB disruption early after ischemia may enhance the movement of compounds from blood to areas close to the ventricular system and participate in delayed neuronal death.     

Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery.

BACKGROUND AND PURPOSE: Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery. METHODS: Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside. RESULTS: With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes. CONCLUSIONS: The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery.     

Microcirculatory changes in the development of the cerebrovascular adaptation]

Recently, long-term cerebrovascular adaptations after unilateral carotid ligation that increase the tolerance of the brain to subsequent episode of ischemia was reported(J Cereb Blood Flow Metab, 1998). However, the pathophysiological mechanisms underlying the phenomenon was unknown. We examined regional cerebral blood flow(rCBF) before, during and after subsequent ischemia in the development of the adaptation. Male Wistar rats(n = 18) were used. Unilateral(right) carotid artery ligation was performed 3 hours(group A: n = 8), 3 days(group B: n = 10) before forebrain ischemia. With bilateral carotid arteries occlusion, mean arterial blood pressure(MABP) was reduced by hypobaric hypotension down to 50 mmHg and maintained constant for 30 min. After hypotension, the experiment continued for 90 min. Local CBF were registered at 25(5 x 5) identical locations by laser Doppler scanning in the cortex during the experiment in bilateral hemispheres(at control phase, after the left carotid artery ligation, during ischemia and after hypotension). The physiological variable such as blood pressure and gas analysis were within normal range in all groups. There were no differences of rCBF between the right and left hemispheres in group A during the experiment. In group A, rCBF of both hemispheres significantly decreased after the ligation of the left carotid artery, during the induced ischemia (P < 0.05), and recovered to the value of before ischemia. Whereas, in group B rCBF of the left side(non-occluded side) decreased after the ligation of the left carotid artery, during the induced ischemia(P < 0.05), and recovered to the value of before ischemia, but rCBF of the right side(occluded side) decreased only during the induced ischemia(P < 0.05) and rCBF of the right side was significantly higher than the left brain after ligation of the carotid artery, during ischemia and after hypotension(P < 0.05). On the basis of these data, we concluded that cerebrovascular adaptations can be acquired by 3 days after unilateral carotid artery occlusion and the tolerance phenomenon is certainly attributed to microcirculatory improvement.     

Arteriogenesis in hypoperfused rat brain.

Experimental and clinical studies have provided evidence for spontaneous and therapeutically induced arteriogenesis after occlusion of major peripheral or cardiac vessels. Such evidence is lacking for the cerebrovascular system. In halothane-anesthetized rats, different degrees of brain hypoperfusion were induced by one- to four-vessel occlusion, that is, one or both common carotid arteries in combination with or without bilateral vertebral artery occlusion. The flow decline was monitored by laser Doppler flowmetry, the residual hemodynamic reserve by testing flow reactivity to ventilation with 6% CO(2) and arteriogenesis by intravascular latex infusion and immunohistochemistry of vascular proliferation and monocyte adhesion. The optimum condition for induction of arteriogenesis was three-vessel (one carotid plus both vertebral arteries) occlusion, which led to reduction of blood flow to about 50% and complete suppression of CO(2) reactivity, but no histologic injury. One week after three-vessel occlusion, the ipsilateral posterior cerebral artery significantly enlarged by 39%, and after 3 weeks by 72%, paralleled by the partial return of CO(2) reactivity and the appearance of immunohistochemical markers of arteriogenesis. Three-vessel occlusion is a reliable model for the induction of arteriogenesis in the adult brain and is a new approach for exploring the potentials of arteriogenesis for the prevention of progressing brain ischemia.     

10例双侧颈动脉重度狭窄或闭塞患者的临床特点分析

目的探讨双侧颈动脉重度狭窄或闭塞患者的临床特点。方法回顾性分析10例双侧动脉重度狭窄或闭塞患者临床特点及血流代偿情况。结果 10例患者中,双侧颈总动脉闭塞和颈内动脉闭塞各1例,双侧颈内动脉重度狭窄5例,一侧闭塞合并一侧重度狭窄3例。临床表现为后循环缺血5例,后循环合并前循环缺血3例,前循环缺血2例。7例行DSA患者,有7例后交通动脉开放,4例前交通动脉开放。结论双侧颈动脉重度狭窄或闭塞患者临床表现以后循环缺血多见,后交通动脉可能为其主要代偿模式。     

Purine catabolites and pial arteriolar diameter in transient cerebral ischemia]

In transient cerebral ischemia, extracellular purine catabolites and pial arteriolar diameter were measured continuously. Ischemia during one hour was induced by unilateral occlusion of left middle cerebral artery in feline. Extracellular purine catabolites were sampled by in vivo brain microdialysis technique from the gray matter at ectosylvian gyrus. These catabolites were analyzed by HPLC system. Simultaneously, reactivity of pial arteriole was observed and its diameter was measured through the cranial window using intravital microscope and width analyzer. Extracellular concentrations of adenosine, inosine, hypoxanthine and xanthine were found to be 0.80 +/- 0.16 microM, 2.01 +/- 0.95 microM, 4.01 +/- 2.73 microM and 3.93 +/- 2.39 microM, respectively. During ischemia, the concentration of adenosine increased 8.7-fold and arteriolar diameter was 170% of the resting state. These findings in extracellular adenosine concentration and pial arteriolar diameter during ischemia support a role of adenosine in regulation of cerebral blood flow. After reperfusion, arteriolar diameter had returned to 120% of the resting state. But 50 min after reperfusion, pial arteriole began to dilate again coincident with the peak of xanthine concentration. These results suggest that free radicals were produced and could affect pial arterioles 50 min after reperfusion.     

Neuropathologic consequences of internal carotid artery occlusion and hemorrhagic hypotension in baboons

We studied eight anesthetized and physiologically monitored adult baboons (Papio cyanocephalus); four were subjected to hemorrhagic hypotension alone and four to hemorrhagic hypotension plus unilateral carotid artery occlusion. Cerebral blood flow was measured using xenon-133, the electroencephalogram was recorded using silver-silver chloride epidural electrodes, and histologic examination was carried out after perfusion-fixation. In the baboons subjected to hypotension alone (mean arterial blood pressure of 28 mm Hg) cerebral blood flow was 28.5 +/- 5.0 ml/100 g/min, whereas in the baboons subjected to hypotension plus unilateral carotid artery occlusion it was 21.8 +/- 1.8 ml/100 g/min at a mean arterial blood pressure of 27 mm Hg. There was no ischemic damage in the former group, but in the latter group there was necrosis in the arterial boundary zones of three baboons and in the distribution of the middle cerebral artery in one. We conclude that, when combined with hypotension, unilateral carotid artery occlusion may lead to hemodynamic ischemia accentuated in the arterial boundary zones of the ipsilateral cerebral hemisphere.