磁共振诊断早期脑缺血的新技术进展--弥散加权成像及灌注加权成像(综述)

磁共振弥散加权成像（ＤＷＩ）和血液灌注成像（ＰＷＩ）是诊断早期脑缺血的新技术；表现弥散系数、脑血流、脑血容量及平均时间是预测缺血灶结果的参数，本文综述了ＤＷＩ及ＰＷＩ的基本原理、测定技术及它们在诊断早期脑缺血方面的应用，分析了ＤＷＩ及ＰＷＩ在诊断早期脑缺血方面的相互关系，认为ＤＷＩ及ＰＷＩ能对早期脑缺血出诊确诊断信息，可反映缺血灶血流动力学的改变。     

Calcium transients in astrocyte endfeet cause cerebrovascular constrictions

Cerebral blood flow (CBF) is coupled to neuronal activity and is imaged in vivo to map brain activation. CBF is also modified by afferent projection fibres that release vasoactive neurotransmitters in the perivascular region, principally on the astrocyte endfeet that outline cerebral blood vessels. However, the role of astrocytes in the regulation of cerebrovascular tone remains uncertain. Here we determine the impact of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in astrocytes on the diameter of small arterioles by using two-photon Ca(2+) uncaging to increase [Ca(2+)](i). Vascular constrictions occurred when Ca(2+) waves evoked by uncaging propagated into the astrocyte endfeet and caused large increases in [Ca(2+)](i). The vasoactive neurotransmitter noradrenaline increased [Ca(2+)](i) in the astrocyte endfeet, the peak of which preceded the onset of arteriole constriction. Depressing increases in astrocyte [Ca(2+)](i) with BAPTA inhibited the vascular constrictions in noradrenaline. We find that constrictions induced in the cerebrovasculature by increased [Ca(2+)](i) in astrocyte endfeet are generated through the phospholipase A(2)-arachidonic acid pathway and 20-hydroxyeicosatetraenoic acid production. Vasoconstriction by astrocytes is a previously unknown mechanism for the regulation of CBF.     

Mapping human visual cortex with positron emission tomography

Positron-emission tomography (PET) can localize functions of the human brain by imaging regional cerebral blood flow (CBF) during voluntary behaviour. Functional brain mapping with PET, however, has been hindered by PET's poor spatial resolution (typically greater than 1 cm). We have developed an image-analysis strategy that can map functional zones not resolved by conventional PET images. Brain areas selectively activated by a behavioural task can be isolated by subtracting a paired control-state image from the task-state image, thereby removing areas not recruited by the task. When imaged in isolation the centre of an activated area can be located very precisely. This allows subtle shifts in response locale due to changes in task to be detected readily despite poor spatial resolution. As an initial application of this strategy we mapped the retinal projection topography of human primary visual cortex. Functional zones separated by less than 3 mm (centre-to-centre) were differentiated using PET CBF images with a spatial resolution of 18 mm. This technique is not limited to a particular brain area or type of behaviour but does require that the increase in CBF produced by the task be both intense and focal.     

芍药苷对局灶性脑缺血模型及血脑屏障的影响

观察芍药苷对脑缺血后再灌流期间血脑屏障及脑缺血神经病理改变症状、脑血流量的影响,采用大鼠局灶性脑缺血再灌流损伤实验模型,以神经行为学、脑组织含水量、病理组织学检查、血脑屏障通透性、脑血流量为指标,与模型对照组比较,局灶性脑缺血1h再复灌3d后,应用芍药苷的各组动物神经行为学、脑组织含水量、组织病理学改变和血脑屏障通透性均得到改善,大脑局部血流量显著增加,芍药苷对脑缺血后脑水肿、血脑屏障、大脑局部血流量具有保护作用。     

利用多模态光学脑成像研究前额叶静息态功能连接

多模态光学脑成像包括近红外光谱及漫射相关谱,前者探测大脑皮层的血氧代谢水平,而后者测量皮层的脑血流.皮层血氧代谢和血流是不同的两类血液动力学参量,可以从不同方面反映大脑的神经活动强度. 本研究利用多模态光学脑成像测量了人脑前额叶的静息态功能连接. 10个正常成年人参加了实验测量,分别用近红外光谱和漫射相关谱在前额叶的相同位置记录了大脑8分钟的自发波动信号,测量覆盖区域包括左侧额下皮层及左背外侧前额叶. 低频段血氧代谢信号（包括含氧血红蛋白、脱氧血红蛋白及总血红蛋白浓度）用来揭示基于血氧信号的静息态功能连接,而相同频段的脑血流信号用来确定基于脑血流的静息态功能连接. 两类血液动力学参量的静息态功能连接均揭示:背外侧前额叶区域内的连接大于背外侧前额叶与额下皮层之间的区域间连接,显示相邻的背外侧前额叶和额下皮层是不同的功能区域. 此外定量比较基于两类血液动力学参量的功能连接发现,基于血氧代谢的连接有更大的连接强度,表明在同一个功能区内,静息时血氧代谢信号的时间同步性更高.     

钩藤散对麻醉犬脑血流量的影响

目的观察钩藤散对脑血流量的影响。方法选择家犬20只,随机分为5组,麻醉后股动脉插管、经压力换能器连接RM-6000型多导生理记录仪,颈总动脉和椎动脉连接MFV-3200型电磁血流量计;打开腹腔寻找十二指肠,3个实验组经十二指肠注入高、中、低剂量的钩藤散浸膏,阴性对照组注入生理盐水,阳性对照组注入尼莫地平(2 mL/kg),分别测定给药前、后脑血流量、收缩压、舒张压、平均动脉压、心率等变化,计算脑血管阻力。结果实验各剂量组及阳性药组,在给药后150 min时脑血流量显著高于(P<0.05)、脑血管阻力显著低于(P<0.05)正常对照组,180 min时有极显著差异(P<0.01或P<0.001),210 min时仍有效。结论钩藤散可明显增加脑部的供血,减少脑血管阻力,从而改善脑部营养,防治老年痴呆。     

针刺留针时间对缺血性中风患者脑血流速度的影响

目的:观察不同留针时间对缺血性中风患者脑血管血流速度的影响,以探索针刺治疗缺血性中风的时效关系的机理。方法:选取缺血性中风急性期、恢复期的患者34例,按轻、中和重度随机分成留针20、40和60 m in 3组。在针刺治疗的疗程前后,对患者进行经颅多普勒检测。结果:针刺可提高缺血性中风患者脑血管血流速度,以留针60 m in作用最为明显。结论:针刺留针时间与脑血管血流速度之间有一定的时效关系。     

Bidirectional control of CNS capillary diameter by pericytes

Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.     

血浆同型半胱氨酸水平与脑小血管病搏动指数相关性研究

目的 探讨血浆同型半胱氨酸(tHcy)水平与脑小血管病患者搏动指数(PI)的相关性.方法 选取脑小血管病患者180例和同期对照组100例,利用化学发光微粒子免疫检测法检测患者血浆tHcy水平;借助颈部血管彩超测定两侧颈动脉血流运动学参数,包括颈动脉最大血流速度(Vmax)、最小血流速度(Vmin)、平均血流速度(Vmean);利用公式PI=(Vmax-Vmin)/Vmean,求得PI.结果 脑小血管病组患者血浆tHcy与患者PI呈正相关(r=0.326,P=0.002),同时与Vmax,Vmin,Vmean呈负相关,而对照组无此相关性.脑白质病变(WML)组患者血浆tHcy水平明显高于腔隙性脑梗死组(LI).结论 血浆tHcy水平与脑小血管病PI有显著的相关性,tHcy是脑小血管病的独立危险因素,可在一定程度上反映脑血管的损伤程度.     

Haemodynamic shear stress activates a K+ current in vascular endothelial cells

The endothelial lining of blood vessels is subjected to a wide range of haemodynamically-generated shear-stress forces throughout the vascular system. In vivo and in vitro, endothelial cells change their morphology and biochemistry in response to shear stress in a force- and time-dependent way, or when a critical threshold is exceeded. The initial stimulus-response coupling mechanisms have not been identified, however. Recently, Lansman et al. described stretch-activated ion channels in endothelial cells and suggested that they could be involved in the response to mechanical forces generated by blood flow. The channels were relatively nonselective and were opened by membrane stretching induced by suction. Here we report whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes. A K+ selective, shear-stress-activated ionic current (designated Ik.s) was identified which is unlike previously described stretch-activated currents. Ik.s varies in magnitude and duration as a function of shear stress (half-maximal effect at 0.70 dyn cm-2), desensitizes slowly and recovers rapidly and fully on cessation of flow. Ik.s activity represents the earliest and fastest stimulus-response coupling of haemodynamic forces to endothelial cells yet found. We suggest that localized flow-activated hyperpolarization of endothelium involving Ik.s may participate in the regulation of vascular tone.     

Glial and neuronal control of brain blood flow

Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches.     

小鼠线栓法局灶性脑缺血再灌注模型的改良

目的：建立可操作性强,重复性好的小鼠局灶性脑缺血再灌注模型。方法：选择昆明白、BABL／C、C57BL／6J小鼠,从颈总动脉插入线栓,可逆地阻断右侧大脑中动脉,通过神经功能评分、TCC染色、HE染色和尼氏染色观察模型的可靠性。结果：线栓阻塞右侧大脑中动脉1h后再灌注24h,多数小鼠出现明显的神经功能异常;TTC染色可见苍白梗死区;HE染色和尼氏染色发现典型的缺血性表现。BABL／C小鼠大脑损伤最为明显,神经功能评分和梗死脑组织百分比与昆明白、C57BL／6J小鼠相比存在显著的统计学差异。结论：改良的线栓法易于操作,可以成功地建立小鼠局灶性脑缺血再灌注模型。     

64排螺旋CT灌注成像在脑梗死早期诊断中的临床应用

探讨64排螺旋CT脑灌注成像（CTPI）对脑梗死超早期诊断的临床价值。对32例超早期脑梗死患者,均于发病6h内行CT平扫、CTPI检查,分析平扫及灌注成像表现,测量缺血区的脑灌注参数值。结果为32例患者中8例头颅CT平扫发现早期梗死征象,所有患者CTPI均发现脑灌注异常。脑梗死中心区脑血流量、脑血容量与对侧差异有极显著性意义（P〈0．01）;半暗带区脑血流量、达峰时间与对侧差异有极显著性意义（P〈0．01）,而脑血容量差异无显著性意义（P〉0．05）。CTPI能够在脑梗死发病的超早期发现病变,明确梗死灶存在及其范围、位置,预测半暗带区域,对脑梗死的早期诊断和治疗有重要价值,具有广泛临床应用前景。     

尼莫地平对蛛网膜下腔出血大鼠脑功能的改善作用

目的探讨尼莫地平对SAH大鼠脑功能改善作用,并分析相关机制.方法采用枕大池二次注血法建立大鼠SAH模型,通过神经行为学评分,经颅多普勒超声检测基底动脉的平均血流速度,HE染色法观察脑形态学改变,脑含水量检测分析尼莫地平对SAH的治疗机制.结果与假手术组相比,SAH组大鼠出现明显的神经运动功能障碍体征,其神经行为学评分明显降低;与SAH组相比,尼莫地平组大鼠神经运动功能障碍体征明显减轻,神经行为评分明显高于SAH组.颅超声多普勒检测结果表明:SAH组大脑基底动脉血流速度明显加快,而经过尼莫地平治疗后,其血流速度明显降低;HE染色发现:SAH组大鼠脑中可见明显的出血灶,神经元数目减少,神经元及神经胶质出现肿胀,尼莫地平能够明显减轻SAH后的脑损伤;大鼠SAH时,脑水含量明显增加,尼莫地平既能减轻血管源性脑水肿症状,又减轻细胞毒性脑水肿症状.结论尼莫地平能改善神经运动功能障碍,其机制与降低基底动脉血流速度、减轻神经细胞、胶质细胞肿胀及减轻脑水肿有关.     

脑Willis环循环的血液动力学研究

建立了一个描述脑循环Ｗｉｌｌｉｓ环血液运动规律的动力学并进一步得到了其状态方程及求解方法，应用该方法不仅可以直接求解定常问题，而且还可以求解不定常问题，该模型不仅反映了脑血管弹性和阻力等动力学参数对脑血流特性的影响，而且还反映了不同病理生理状态下脑血注的代偿功能，最后，通过研究动力学参数变化对输入阻抗的影响发现，一侧颈动脉输入阻抗已不仅和该侧血管力学特性有关，而且还受对侧乃至后循环血管及血流特性的     

Central serotonergic nerves project to the pial vessels of the brain

Serotonin is strongly implicated in the aetiology of several cerebrovascular (circulatory) diseases, including stroke, migraine and vasospasm. Previous studies have suggested the existence of an indoleaminergic system of perivascular nerves in large cerebral arteries of the lamprey. In addition, some authors have observed that cerebral arteries (such as the vertebrobasilar system of the rabbit) and microvessels may take up serotonin and 5-hydroxytryptophan in various species. However, neither large cerebral arteries nor microvessels (primarily capillaries) directly control, or change, cerebral blood flow; as in other vascular beds, it is the arterioles and small arteries that are the major resistance elements. We report here on the presence of a central serotonergic innervation of pial arteries and arterioles in the rat, using immunocytochemical and neurochemical techniques. The fibres seem to have a central neuronal origin, emanating from both median and dorsal raphé nuclei. This perivascular serotonergic innervation may have a role both in the normal regulation of the cerebral circulation and in pathological conditions.     

脑缺血动物模型的研究进展

缺血性脑血管病是由于脑动脉硬化等原因,使脑动脉管腔狭窄,血流减少或完全阻塞,脑部血液循环障碍,脑组织受损而发生的一系列症状,是临床医学的难题.制备脑缺血动物模型对缺血性脑学管病的病理生理学机制的探讨、特效药的筛选、最佳治疗方法的建立就显得尤为重要,本文就常用的脑缺血动物模型的选择、制备及影响因素做一综述.     

TCD study of hemodynamic changes in PCA response to photic stimulation

OBJECTIVES: During visual stimulation, the elevated metabolism rate will couple with increase of blood flow velocity(BFV) in posterior cerebral artery(PCA). This study with TCD was aimed to investigate whether the coupling might change according to the different vasoneuronal conditions. METHODS: Ninety-nine volunteers including 24 hypertension(HT) patients and 2 patients suffering from both HT and diabetes mellitus (DM) were enrolled in this trial. BFV and pulse indexes(PI) in P2 segments of PCA on both sides were monitored during visual stimulation. RESULTS: In all subjects, Mean BFV increased and PI went down in response to visual stimulation. The percentages of changes (deltaV and deltaP) of both mean BFV and PI were larger in young group( < 55 years old) than in old one(> or = 55 years old). There was significant positive correlation between deltaV and deltaP. Multivariated regression analysis did not show HT and DM, but age related to deltaV(deltaP). We did not find significant difference of deltaV(deltaP) between left and right sides. CONCLUSIONS: Blood flow velocity in PCA P2 segment increased due to decreased cerebrovascular resistance during visual stimulation and the response weakened with aging of the patient.     

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in hindlimb ischemia of dogs

A preclinical study of treating peripheral srtery occlusive disease(PAD) was performed by using a hepatocyte growth factor(HGF) gene-expressing vector,plasmid pUDKH,in a dog model with complete ischemia of one hindlimb.After ligation of femoral artery of one hindlimb,pUDKH was transferred directly into the ischemic limb muscles.The angiogenic activity of the plasmid pUDKH was evaluated.On D 30 after injecting once of pUDKH at differ-ent doses into local muscles immediately after operation,the degree of augmentation of collateral vessel formation was significantly greater than that treated by blank vector.In addition,the blood flow rate of femoral artery in dogs treated with pUDKH was recovered on D90,while the folw rate was only 1/5 tp 1/3 in control dogs.The pulse amplitude of pUDKH-treated dogs was recovered on D90,but it was hardly detectable in most of the control dogs.The side effects of intramuscular transfection of pUDKH were also investi-gated,and no significant positive change was found.It is suggested that angiogenesis induced by HGF gene has the potential for clincal use in the treatment of peripheral arte-rial diseases.     

体外反搏提高舒张压在心、脑及小肠系膜动脉中的不同表现

通过观察体外反搏提高舒张压在心、脑及肠系膜动脉中的不同表现，发现体外反搏更能有效提高冠状动脉及脑动脉灌注压，而在小肠系膜动脉中压力则表现波动性较大．结果表明体外反搏更有利于提高心脑血管的灌注．