动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的低温治疗

脑血管痉挛(cerebral vasospasm,CVS)是导致动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者死亡和残疾的主要原因之一.人们对SAH后CVS进行了广泛的研究,认为红细胞分解产物、血管内皮功能障碍以及分子机制在其发病起关键作用.目前对脑血管痉挛的治疗尚无确切治疗方法,近年来人们尝试应用低温治疗脑血管痉挛,现就SAH后CVS的病理生理机制和低温对于CVS的治疗进展作一综述.     

蛛网膜下腔出血后脑血管痉挛与c-myc、c-fos、c-jun表达的关系

目的 通过采用兔基底动脉穿刺建立的蛛网膜下腔出血（SAH）模型，系统研究蛛网膜下腔出血后脑血管痉挛发生（CVS）的情况，脑血管痉挛的病理损害。方法应用逆转录-聚合酶链反应（RT-PCR）及免疫组织化学的方法分别检测受累动脉c-myc、c-fos、c-jun mRNA及c-myc、c-fos，c-jun蛋白表达情况。结果 SAH后CVS发生过程中，在8h后相继出现c-myc、c-fos、c-jun mRNA的明显表达，c-myc、c-fos、c-jun的蛋白表达落后于基因表达，免疫组织化学显示c-myc、c-fos、c-jun主要表达在血管内皮细胞及平滑肌细胞。基因与蛋白表达均具有明显的时间依赖性，并与病理损害程度相平行。结论 揭示SAH后CVS的发生可能与细胞凋亡的发生有关，为防治SAH后CVS提供了一个研究方向。     

Molecular keys to the problems of cerebral vasospasm

The mechanisms responsible for subarachnoid hemorrhage (SAH)-induced vasospasm are under intense investigation but remain incompletely understood. A consequence of SAH-induced vasospasm, cerebral infarction, produces a nonrecoverable ischemic tissue core surrounded by a potentially amenable penumbra. However, successful treatment has been inconsistent. In this review, we summarize the basic molecular biology of cerebrovascular regulation, describe recent developments in molecular biology to elucidate the mechanisms of SAH-induced vasospasm, and discuss the potential contribution of cerebral microcirculation regulation to the control of ischemia. Our understanding of the pathogenesis of SAH-induced vasospasm remains a major scientific challenge; however, molecular biological techniques are beginning to uncover the intracellular mechanisms involved in vascular regulation and its failure. Recent findings of microvascular regulatory mechanisms and their failure after SAH suggest a role in the development and size of the ischemia. Progress is being made in identifying the various components in the blood that cause SAH-induced vasospasm. Thus, our evolving understanding of the underlying molecular mechanism may provide the basis for improved treatment after SAH-induced vasospasm, especially at the level of the microcirculation.     

Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the cerebral basilar artery of rats with subarachnoid hemorrhage,and the effect of acetylcholine

Background

There are complex interactions between acetylcholine (ACh), the suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is known about their dynamic expression or their effects on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify the dynamic expression of SOCS-3 and cytokines after SAH, as well as the relationships between the levels of SOCS-3, cytokines, and ACh.

Methods

The rat model of single cisterna magna injection was used to mimic acute SAH. The degree of CVS was indicated by lumen diameter and artery wall thickness under H&E staining. A semi-quantitative immunohistochemical analysis method was used to clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of IL-6 and IL-10 in cerebrospinal fluid.

Results

We found that SOCS-3 expression levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at 48 h. IL-10 levels increased during the first 6 h after SAH, after which this increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment counteracted the activity of ACh.

Conclusions

Taken together, these data indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related mechanism, and that CVS following SAH could be reversed by the intraventricular injection of ACh.     

Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation

Cerebral vasospasm is a common, formidable, and potentially devastating complication in patients who have sustained subarachnoid hemorrhage (SAH). Despite intensive research efforts, cerebral vasospasm remains incompletely understood from both the pathogenic and therapeutic perspectives. At present, no consistently efficacious and ubiquitously applied preventive and therapeutic measures are available in clinical practice. Recently, convincing data have implicated a role of inflammation in the development and maintenance of cerebral vasospasm. A burgeoning (although incomplete) body of evidence suggests that various constituents of the inflammatory response, including adhesion molecules, cytokines, leukocytes, immunoglobulins, and complement, may be critical in the pathogenesis of cerebral vasospasm. Recent studies attempting to dissect the cellular and molecular basis of the inflammatory response accompanying SAH and cerebral vasospasm have provided a promising groundwork for future studies. It is plausible that the inflammatory response may indeed represent a critical common pathway in the pathogenesis of cerebral vasospasm pursuant to SAH. Investigations into the nature of the inflammatory response accompanying SAH are needed to elucidate the precise role(s) of inflammatory events in SAH-induced pathologies.     

Evaluation of cerebral vasospasm in patients with subarachnoid hemorrhage using single photon emission computed tomography

Cerebral vasospasm (CVS) occurs as a result of the breakdown in cerebral autoregulation mechanisms. Because cerebral vasospasm can occur after subrachnoid hemorrhage (SAH), it is important to evaluate borderline perfusion. Evaluation of borderline vascular insufficiency is important to reduce ischemic complications. In this study 25 patients with SAH were investigated by somatosensory evoked potentials (SEP), computed tomography (CT), digital subtraction angiography (DSA) and single photon emission computed tomography (SPECT) in order to predict borderline ischemic areas. Clinical grades were also correlated with these investigations. Thirteen patients had symptomatic vasospasm and 15 patients had angiographic vasospasm. SPECT showed hypoperfusion in 22 out of 25 patients. CT predicted CVS in 8 of these 22 patients. Our study shows that brain perfusion SPECT is a non-traumatic, non-invasive, non-allergic, inexpensive method for the prediction of cerebral vasospasm. We conclude that brain SPECT with Tc-99m HM-PAO is an accessible technique that can demonstrate varying degrees of regional tissue hypoperfusion in patients with delayed ischemic deficits due to CVS following SAH.     

Role of Akt signaling pathway in delayed cerebral vasospasm after subarachnoid hemorrhage in rats

Background

Akt plays an important role in cell survival, proliferation, apoptosis and other activities. It also has been involved in maintaining smooth muscle cell contraction phenotypes in vitro and in vivo. Recent studies have focused on the inhibition of Akt in acute vasospasm and neuronal apoptosis after subarachnoid hemorrhage (SAH). However, its role in delayed cerebral vasospasm (DCVS) has not been reported.

Methods

In this study, using a “two-hemorrhage” rat model of SAH, we examined the expression of p-Akt and the formation of vasospasm in the basilar arteries. To investigate the possible role of Akt in phenotypic switching, we performed immunohistochemical staining to examine expressions of SMα-actin and proliferating cell nuclear antigen (PCNA), markers of smooth muscle phenotypic switching.

Results

We found that the basilar arteries exhibited vasospasm after SAH and that vasospasm became most severe on day 7 after SAH. Elevated protein expression of p-Akt was detected 4 days after SAH induction, peaked on day 7, and recovered on day 21, which was in a parallel time course to the development of DCVS. Moreover, results of immunohistochemical staining revealed enhanced expression of PCNA but gradual reduction in expression of SMα-actin from day 1 to day 7 after SAH; then, the expressions of PCNA and SMα-actin gradually recovered until day 21.

Conclusions

These results support a novel mechanism in which the Akt signaling pathway plays an important role in the proliferation of smooth muscle cells (SMCs) rather than inducing phenotype switching in basilar arteries, which promotes the development of DCVS after SAH.     

Severe cerebral vasospasm caused by non-aneurysmal subarachnoid hemorrhage treatment with transluminal balloon angioplasty.

Non-aneurysmal subarachnoid hemorrhage (NSAH) is a benign form of subarachnoid hemorrhage (SAH). The angiographic changes of cerebral vasospasm (CVS) are uncommon in patients with this type of SAH. NSAH is uniformly associated with an excellent outcome without associated rebleeding or symptomatic CVS. We report a patient with NSAH who developed severe and diffuse CVS. He was treated with transluminal balloon angioplasty because he has been refractory to conventional treatment measures for CVS.     

Up-regulation of parathyroid hormone receptor in cerebral arteries after subarachnoid hemorrhage in monkeys

OBJECTIVE: Complementary deoxyribonucleic acid array analysis was used to determine whether vasospasm after subarachnoid hemorrhage (SAH) is associated with changes in gene expression. METHODS: Right SAHs were created in three monkeys, and the right and left middle cerebral arteries were collected 3, 7, or 14 days after SAH. Vasospasm was assessed by angiography performed on Day 0 and at tissue harvest. A complementary deoxyribonucleic acid array containing 5184 genes was used to screen for changes in gene expression by comparing the right and left middle cerebral arteries. RESULTS: There was significant expression (greater than fivefold expression of messenger ribonucleic acid compared with internal standard control) of 537 genes (10%) in the middle cerebral arteries. One hundred sixty-four genes (31%) did not change significantly, and 373 (69%) were differentially expressed at 3, 7, or 14 days after SAH. These 373 genes changed from 1.2- to 7-fold as compared with control arteries. The most common pattern was a progressive increase with increased time after SAH. The functions of differentially expressed genes included the regulation of gene expression, cell proliferation, inflammation, membrane proteins and receptors, kinases, and phosphatases. There was a marked increase in parathyroid hormone and parathyroid hormone receptor with time after SAH. Immunoblotting demonstrated a significant increase in parathyroid hormone receptor protein. CONCLUSION: The up-regulation of these proteins involved in vascular relaxation suggests that they may play a role in vasospasm. The progressive increase in messenger ribonucleic acids involved in the functions noted suggests that the pathogenesis of cerebral vasospasm involves cell proliferation, inflammation, and possibly smooth muscle phenotype change.     

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.     

上胸段硬膜外交感神经阻滞对兔蛛网膜下腔出血诱发脑血管痉挛的影响

目的 探讨上胸段硬膜外交感神经阻滞对兔蛛网膜下腔出血(SAH)诱发脑血管痉挛的影响.方法 日本大耳白兔24只,雌雄不拘,体重2.0～2.6 kg,随机分为3组(n=8).对照组(C组)枕大池注射生理盐水1 ml/kg,硬膜外腔注射生理盐水0.5 ml/2 h;S组枕大池注射自体动脉血1 ml/kg,硬膜外腔注射生理盐水0.5 ml/2 h;H组枕大池注射自体动脉血1 ml/kg,硬膜外腔注射0.5%利多卡因0.5 ml/2 h.记录家兔实验第4、5、6天进食量和神经功能状态,经颅多普勒超声测定实验前(T0)和实验第7天(T1)颈总动脉血流速度[平均血流速度(Vm)、收缩期峰血流速度(Vs)、舒张末血流速度(Vd)]搏动指数(PI)、阻力指数(RI),连续监测心率(HR)、平均动脉压(MAP)、心电图.结果 与C组相比,S组进食量下降和神经功能障碍发生率增加(P＜0.05);与S组相比,H组进食量下降和神经功能障碍发生率减少(P＜0.05);与T0时相比,T1时S组Vs、Vm及Vd升高,PI及RI降低,H组HR及上述指标降低(P＜0.05);与C组相比,T1时S组Vs、Vm及Vd升高,PI及RI降低,H组HR及上述指标降低(P＜0.05);与S组相比,T1时H组HR及上述指标降低(P＜0.05).结论 0.5%利多卡因上胸段硬膜外交感神经阻滞可抑制交感神经兴奋,从而改善兔SAH后脑血管痉挛.