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Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2).克拉生坦,一种内皮素受体拮抗剂,在接受手术夹闭的颅内动脉瘤性蛛网膜下腔出血患者中的应用:一项随机、双盲、安慰剂对照的 3 期临床试验(CONSCIOUS-2)。
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Subarachnoid Hemorrhage Induces Gliosis and Increased Expression of the Pro-inflammatory Cytokine High Mobility Group Box 1 Protein.蛛网膜下腔出血诱导神经胶质增生和促炎细胞因子高迁移率族蛋白 1 表达增加。
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The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.扩散性抑制、扩散性去极化和扩散性缺血在神经疾病中的作用。
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Fundamental increase in pressure-dependent constriction of brain parenchymal arterioles from subarachnoid hemorrhage model rats due to membrane depolarization.蛛网膜下腔出血模型大鼠脑实质小动脉压力依赖性收缩的基本增加是由于膜去极化。
Am J Physiol Heart Circ Physiol. 2011 Mar;300(3):H803-12. doi: 10.1152/ajpheart.00760.2010. Epub 2010 Dec 10.
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Glial and neuronal control of brain blood flow.神经胶质细胞和神经元对脑血流的控制。
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Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury.皮质扩散性抑制在神经疾病中的临床意义:偏头痛、恶性中风、蛛网膜下腔和颅内出血以及外伤性脑损伤。
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Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone.蛛网膜下腔出血后钙火花活动减少使大脑动脉张力失去 BK 通道的控制。
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8
Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction.星形细胞终足 Ca2+ 和 BK 通道决定小动脉的舒张和收缩。
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3811-6. doi: 10.1073/pnas.0914722107. Epub 2010 Feb 2.
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Bleeding in the brain: Killer waves of depolarization in subarachnoid bleed.脑内出血:蛛网膜下腔出血中的去极化致死波。
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10
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.皮质扩展性缺血是一种与动脉瘤性蛛网膜下腔出血患者缺血性损伤相关的新过程。
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蛛网膜下腔出血可使大鼠大脑皮层中神经诱发的血管舒张转变为血管收缩。

Subarachnoid blood converts neurally evoked vasodilation to vasoconstriction in rat brain cortex.

作者信息

Koide Masayo, Bonev Adrian D, Nelson Mark T, Wellman George C

机构信息

Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT 05405-0068, USA.

出版信息

Acta Neurochir Suppl. 2013;115:167-71. doi: 10.1007/978-3-7091-1192-5_32.

DOI:10.1007/978-3-7091-1192-5_32
PMID:22890664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3684063/
Abstract

The matching of blood flow to regional brain function, called functional hyperemia or neurovascular coupling, involves the coordinated activity of neurons, astrocytes, and parenchymal arterioles. Under physiological conditions, localized neuronal activation leads to elevated astrocyte endfoot Ca(2+) and vasodilation, resulting in an increase in cerebral blood flow. In this study, we examined the impact of subarachnoid hemorrhage (SAH) on neurovascular coupling. SAH model rats received two injections of autologous blood into the cisterna magna 24 h apart. Cortical brain slices from SAH model animals were prepared 4 days after the initial blood injection. Arteriolar diameter and astrocyte endfoot Ca(2+) were simultaneously measured using two-photon microscopy. As expected, neuronal activity evoked by electrical field stimulation (EFS) caused an elevation in endfoot Ca(2+) and vasodilation in brain slices from control animals. However, in brain slices from SAH animals, EFS induced a similar increase in astrocyte endfoot Ca(2+) that caused arteriolar constriction rather than vasodilation. Vasoconstriction was observed in approximately 90% of brain slices from SAH animals in response to EFS, with 40% exhibiting a sustained vasoconstriction, 30% exhibiting a transient vasoconstriction -(diameter restored within 1 min after EFS), and 20% responded with a biphasic response (brief vasodilation followed by -vasoconstriction). This inversion of neurovascular coupling may play a role in the development of neurological deficits following SAH.

摘要

血流与局部脑功能的匹配,即所谓的功能性充血或神经血管耦合,涉及神经元、星形胶质细胞和实质小动脉的协同活动。在生理条件下,局部神经元激活会导致星形胶质细胞终足Ca(2+)升高和血管舒张,从而使脑血流量增加。在本研究中,我们研究了蛛网膜下腔出血(SAH)对神经血管耦合的影响。SAH模型大鼠在相隔24小时的时间里分两次向小脑延髓池注射自体血。在首次注射血液4天后制备SAH模型动物的大脑皮质脑片。使用双光子显微镜同时测量小动脉直径和星形胶质细胞终足Ca(2+)。正如预期的那样,电场刺激(EFS)诱发的神经元活动导致对照动物脑片中终足Ca(2+)升高和血管舒张。然而,在SAH动物的脑片中,EFS诱导星形胶质细胞终足Ca(2+)出现类似的增加,但却导致小动脉收缩而非血管舒张。在SAH动物的约90%脑片中观察到对EFS的血管收缩反应,其中40%表现为持续性血管收缩,30%表现为短暂性血管收缩(EFS后1分钟内直径恢复),20%表现为双相反应(短暂血管舒张后接着血管收缩)。这种神经血管耦合的反转可能在SAH后神经功能缺损的发生中起作用。