动脉瘤性蛛网膜下腔出血后神经元损伤机制的研究进展（英文）

动脉瘤性蛛网膜下腔出血(a SAH)是脑卒中最严重的表现形式之一。颅内动脉瘤破裂后血液瘀滞在脑蛛网膜下腔,引起多种病理生理改变,包括脑积水、细胞凋亡、血脑屏障功能障碍、血管痉挛、微血栓形成和皮层扩散性抑制,这些机制相互作用并贯穿于整个脑损伤过程。近年来,临床试验逐渐关注a SAH发生后的两个阶段:早期脑损伤(EBI)和延迟性脑缺血(DCI)。这两个时期是导致神经元损伤的主要阶段,并与患者的预后密切相关。我们就近年来蛛网膜下腔出血后脑损伤的机制作一简要总结,主要讨论EBI和DCI在神经损伤中的作用。     

动脉瘤性蛛网膜下腔出血后脑血管痉挛患者的疗效观察及护理

目的：探讨蛛网膜下腔出血后脑血管痉挛患者的疗效观察及护理。方法回顾性分析136例动脉瘤性蛛网膜下腔出血患者临床资料。结果136例aSAH患者例共51例患者出现CVS,占37.5,其中痊愈24例,好转19,留下严重后遗症6,死亡2例,其中1例患者动脉瘤再次破裂出血而死亡。结论早期观察、严密监测生命体征、加强治疗过程中的护理,是降低SAH合并CVS患者死亡率和致残率的重要措施。     

阿斯匹林与动脉瘤性蛛网膜下腔出血后迟发性脑缺血

０１４阿斯匹林与动脉瘤性蛛网膜下腔出血后迟发性脑缺血［英］／ＪｕｖｅｌｄＳ／／ＪＮｅｕｒｏｓｕｒｇ．－１９９５，８２（６）．－９４５～９５２动脉瘤性蛛网膜下腔出血（ＳＡＨ）致残率和死亡率均很高，主要原因是ＳＡＨ后的血管痉孪，而ＳＡＩ后脑血管痉挛及迟发...     

U74389G预防狗蛛网膜下腔出血后脑血管痉挛

颅内动脉瘤破裂后的主要并发症包括蛛网膜下腔出血（ＳＡＨ）本身所引起的脑损害以及蛛网膜下腔出血后第７天所发生的脑血管痉挛。其发生机理为：颅内动脉瘤破裂后，去氧自由基通过直接作用于动脉壁而导致血管痉挛；此外，还可引起蛛网膜下腔红细胞脂氧化而诱发血管收缩。Ｕ７４３８９Ｇ是一种有力的脂氧化抑制剂和去氧自由基清除剂。本研究验证了去氧自由基和脂氧化在实验性狗蛛网膜下腔出血中引起血管痉挛的相关作用。１６只狗实验前均进行了脑血管造影，于第２天将新鲜血液注入到延髓池诱发蛛网膜下腔出血。随机将１６只狗分为两组：第一…     

蛛网膜下腔出血研究:从脑血管痉挛到早期脑损伤

蛛网膜下腔出血(Subarachnoid hemorrhage,SAH)是一种致命性脑血管事件。因人们曾认定SAH后脑血管痉挛(cerebral vasospasm,CVS)为主要致病机制,传统研究多关注SAH后大血管的病理变化。但仅控制CVS不能有效改善SAH患者预后,这提示存在其他致病机制。近年来人们提出早期脑损伤(early brain injury,EBI)的概念,即从SAH发生到CVS出现前脑组织受到的损伤,其可能是SAH不良预后的主因。本文试回顾SAH研究历程并从细胞电生理变化、血脑屏障损坏、炎症和凋亡等方面概述EBI研究的主要进展。     

血管内栓塞颅内动脉瘤围手术期护理

颅内动脉瘤是颅内动脉管腔局部的异常扩张，是蛛网膜下腔出血（SAH）的主要原因，现代神经放射学的发展，使绝大多数的颅内动脉瘤都能通过血管内栓塞而治愈，从而免除开颅手术。我院自2004年1月至2006年6月，采用电解可脱式弹簧圈（GuglimiDetachable Coil，GDC）血管内途径栓塞治疗颅内动脉瘤蛛网膜下腔出血病人48例，均取得了良好的手术效果，现将围手术期护理体会报告如下。     

序贯性综合疗法防治蛛网膜下腔出血后腔血管痉挛

目的讨腰大池置管外引流、罂粟碱鞘内注射联合静滴法舒地尔对动脉瘤性蛛网膜下腔出血(aSAH)术后脑血管痉挛(CVS)的临床疗效和安全性。方法按入院先后顺序将68例aSAH患者随机分为两组,两组患者均在常规治疗基础上,1w内行颅内动脉瘤夹闭术或栓塞术,术后对照组给以尼莫地平注射液治疗,疗程14d。治疗组术后给以腰大池置管脑脊液持续外引流,持续4~14d,鞘内注射罂粟碱,共3d,同时静滴法舒地尔2w,观察治疗前后患者的临床表现,神经系统评分及并发症,血生化指标,脑血管痉挛状态和临床有效率。结果与对照组比较,治疗组患者的临床症状缓解时间明显缩短(P<0.05);脑梗塞、脑积水发生率减少(P<0.01);经颅多普勒TCD脑血管痉挛指标VMCA/VICA低于对照组(P<0.05),两组治疗后神经功能缺损程度评分比较,也有统计学差异,治疗组总有效率为94.1%,对照组为79.4%,两组均未发生任何严重不良反应。结论序贯综合疗法防治蛛网膜下腔出血后脑血管痉挛与经典尼莫地平相比较,临床疗效更优,安全性亦较高。     

颅内动脉瘤并发蛛网膜下腔出血脑积水的综合治疗

脑动脉瘤性蛛网膜下腔出血(SAH)后急性或慢性脑积水的发生严重影响着动脉瘤患者的预后.这种类型的脑积水主要是由于SAH后脑脊液(CSF)分泌过多或吸收障碍而导致CSF循环受阻,是脑动脉瘤破裂的常见并发症之一.     

脑动脉瘤性蛛网膜下腔出血后脑积水的综合治疗

脑动脉瘤性蛛网膜下腔出血(SAH)后急性或慢性脑积水的发生严重影响着动脉瘤患者的预后.这种类型的脑积水主要是由于SAH后脑脊液(CSF)分泌过多或吸收障碍而导致CSF循环受阻,是脑动脉瘤破裂的常见并发症之一.虽然SAH后慢性脑积水的形成机制尚未完全明确,但蛛网膜下腔积血对CSF循环的影响足脑积水形成的主要因素,由于其发生发展与SAH密切相关.我院从2004年-2007年对23例动脉瘤并发脑积水的患者予以综合方法治疗,取得了良好效果.现报告如下:     

显微镜下动脉瘤夹闭术联合腰椎穿刺与腰大池持续引流治疗动脉瘤性蛛网膜下腔出血的临床应用价值比较

目的对比分析显微镜下动脉瘤夹闭术联合腰椎穿刺与腰大池持续引流治疗动脉瘤性蛛网膜下腔出血(aSAH)的临床应用价值。方法选取本院2016年3月至2019年10月收治且经DSA或急诊CT血管造影(CTA)确诊的64例aSAH患者作为研究对象,根据手术方法的不同分为对照组和观察组,每组各32例。对照组患者采用显微镜下动脉瘤夹闭术联合腰椎穿刺治疗,观察组患者采用显微镜下动脉瘤夹闭术联合腰大池持续引流治疗。比较两组患者的临床疗效及感染、脑积水等并发症发生情况。结果观察组患者治疗后恢复良好率明显高于对照组,致残率和并发症发生率显著低于对照组,差异具有统计学意义(P0.05)。结论采用显微镜下动脉瘤夹闭术联合腰大池持续引流治疗aSHA患者可有效降低致残率和术后并发症发生率,改善患者预后。     

Potentials of magnesium treatment in subarachnoid haemorrhage.

Subarachnoid hemorrhage from a ruptured aneurysm is a subset of stroke. The young age (median 55 years) and poor outcome (50% of patients die; 30% of survivors remain dependent) explain why in the population the loss of productive life years from aneurysmal subarachnoid hemorrhage (SAH) is as large as that from brain infarcts, the most common type of stroke. Ischemia plays an important role in the pathophysiological process after SAH. A period of global cerebral ischemia firstly occurs in the acute phase, immediately after rupture of the aneurysm, due to acute vasoconstriction and elevated intracranial pressure, which leads to a drop in perfusion pressure. This is quite distinct from the secondly, delayed cerebral ischemia (DCI), which is focal or multi-focal. DCI usually occurs between 4 and 10 days after the initial bleeding, has a gradual onset and is multi-focal, and is an important cause of death and dependency after SAH. The interval between the bleeding and the onset of ischemia provides an opportunity for preventive treatment. Magnesium is readily available, inexpensive and has a well-established clinical profile in obstetrical and cardiovascular practice. It is beneficial in the treatment of eclampsia, a disease with a pathophysiology comparable to DCI after subarachnoid hemorrhage. Neuroprotective mechanisms of magnesium include inhibition of the release of excitatory amino-acids and blockade of the NMDA-glutamate receptor. Magnesium is also a non-competitive antagonist of voltage dependent calcium channels, has cerebrovascular dilatory activity and is an important co-factor of cellular ATPases, including the Na/K-ATPase. Magnesium can reverse delayed cerebral vasospasm and reduces the extent of acute ischemic cerebral lesions after experimental subarachnoid hemorrhage in rats. In this article we discuss the neuroprotective potency of magnesium in SAH by describing the pathophysiology of ischaemia after SAH and the many ways magnesium may interfere with this.     

The CSF concentration of ADMA,but not of ET-1, is correlated with the occurrence and severity of cerebral vasospasm after subarachnoid hemorrhage

Under physiological conditions, vasoconstrictors and vasodilators are counterbalanced. After aneurysmal subarachnoid hemorrhage (SAH) disturbance of this equilibrium may evoke delayed cerebral vasospasm (CVS) leading to delayed cerebral ischemia (DCI). Most studies examined either the vasoconstrictor endothelin-1 (ET-1) or the vasodilative pathway of nitric oxide (NO) and did not include investigations regarding the relationship between vasospasm and ischemia. Asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), decreases the concentration of NO. Studies have correlated increasing concentrations of ADMA with the course and degree of CVS after SAH. We sought to determine, if ADMA and endothelin-1 (ET-1) are associated with CVS and/or DCI after SAH. CSF concentrations of ADMA and ET-1 were retrospectively determined in 30 patients after SAH and in controls. CVS was detected clinically and by arteriogaphy. DCI was monitored by follow-up CT scans. 17 patients developed arteriographic CVS and 4 patients developed DCI. ADMA but not ET-1 concentrations were correlated with occurrence and degree of CVS. However, ET-1 concentrations were correlated with WFNS grade on admission. Neither ADMA nor ET-1 correlated with DCI in this cohort. ET-1 concentrations seem to be associated with the impact of the SAH bleed. ADMA may be directly involved in the development and resolution of CVS after SAH via inhibition of NOS disturbing the balance of vasodilative and -constrictive components.     

Are isofurans and neuroprostanes increased after subarachnoid hemorrhage and traumatic brain injury?

Current diagnostic tools to assess neurological injury after aneurysmal subarachnoid hemorrhage (aSAH) and traumatic brain injury (TBI) have poor discriminatory abilities. Free radicals are associated with the pathophysiology of secondary damage after brain trauma. We examined cerebrospinal fluid (CSF) lipid markers of oxidative stress, isofurans (IsoFs), F(4)-neuroprostanes (F(4)-NeuroPs), and F(2)-isoprostanes (F(2)-IsoPs), in two case-controlled studies in patients with aSAH or severe TBI. Patients with aSAH (n=18) or TBI (n=18) were age and gender matched with separate control groups. CSF samples were collected from patients within 24?h of the injury. CSF IsoFs and F(4)-NeuroPs were increased in aSAH patients compared with their controls. In TBI patients, IsoFs and F(4)-NeuroPs were increased compared with their controls. F(2)-IsoPs were increased in aSAH patients, but not in TBI patients, compared with their respective controls. CSF IsoFs and F(4)-NeuroPs are consistently increased after a catastrophic central nervous system injury. These results suggest their measurement may enhance the management of unconscious patients in neurological care.     

Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function

The purpose of this study was to evaluate the neuroprotective effects of astaxanthin on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) in rats and to explore possible molecular mechanisms. Experimental SAH model was introduced in adult male SD rats by injecting autologous arterial blood into the prechiasmatic cistern. Astaxanthin (75?mg/kg bodyweight) or olive oil was administered by oral gavage at 3?h after SAH. Our results showed that astaxanthin attenuated SAH-induced cerebral vasospasm and reduced neuronal apoptosis. Astaxanthin inhibited mitochondria-associated neuron apoptosis in the prefrontal cortex after SAH: increased mitochondrial membrane potential, decreased Bax/Bcl-2 ratio, inhibited cytochrome C release in cytoplasm, and suppressed caspase-3 enzyme activity. Furthermore, the cerebral expression levels of synaptic proteins (Synapsin-1, postsynaptic density-95 and growth-associated protein-43) and nerve growth and neuronal differentiation factors (brain-derived neurotropic factor and purine-rich binding protein-alpha) were reduced following SAH. Astaxanthin partly restored their expression. In conclusion, our current work demonstrates that astaxanthin attenuates SAH-induced EBI, possibly by improving neuronal survival and mitochondrial function.     

Metabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage correlate with vasospasm and clinical outcome: a pattern-recognition 1H NMR study

Following subarachnoid haemorrhage the most significant complication is sustained cerebral vascular contraction (vasospasm), which may result in terminal brain damage from cerebral infarction. Despite this, the biochemical cause of vasospasm remains poorly understood. In this study, the global high-concentration metabolite composition of CSF has been correlated with patient outcome after subarachnoid haemorrhage using multivariate statistics and 1H NMR spectroscopy. In total, 16 patients with aneurysmal subarachnoid haemorrhage (aSAH) were compared with 16 control patients who required a procedure where CSF was obtained but did not have aSAH. Multivariate statistics readily distinguished the aSAH group from the heterogeneous control group, even when only those controls with blood contamination in the CSF were used. Using principal components analysis and orthogonal signal correction, vasospasm was correlated to the concentrations of lactate, glucose and glutamine. These pattern recognition models of the NMR data also predicted Glasgow Coma Score (54% within +/- 1 of the actual score on a scale of 1-15 for the whole patient group), Hunt and Hess SAH severity score (88% within +/- 1 of the actual score on a scale of 1-5 for the aSAH group) and cognitive outcome scores (78% within +/- 3 of the actual score on a 100% scale for the whole patient group). Thus, the approach allowed the prediction of outcome as well as confirming the presence of aSAH.     

小胶质细胞在蛛网膜下腔出血后脑损伤中作用机制的研究进展

小胶质细胞是位于中枢的单核巨噬细胞系统成员,对维持中枢神经系统的稳态有重要意义。蛛网膜下腔出血（SAH）是脑卒中的一种亚型,其发生后会造成72 h内早期脑损伤,以及SAH后3～15 d迟发性脑损伤。以往认为,血管痉挛在SAH后脑损伤中发挥重要作用,但脑损伤中的炎症反应近年逐渐受到重视,其中小胶质细胞可在SAH后早期和延迟相脑损伤的炎症反应中向不同方向极化,既可发挥促炎作用,也可产生神经保护作用。我们综述近几年小胶质细胞在SAH后脑损伤中发挥的作用及相关治疗靶点的研究进展及相关热点,为临床处理该类疾病提供潜在治疗靶点。     

Glycyrrhizic acid confers neuroprotection after subarachnoid hemorrhage via inhibition of high mobility group box-1 protein: A hypothesis for novel therapy of subarachnoid hemorrhage

Subarachnoid hemorrhage usually results in poor clinical outcome and devastating neurological deficits. The early brain injury and delayed vasospasm after subarachnoid hemorrhage (SAH) are involved in the poor prognosis to the patients, while the mechanisms have not been well elucidated. Previous studies found an up-regulation of Toll-like receptor 4 (TLR4), inflammatory factors and high-mobility group box 1 (HMGB1) in the cortex after SAH. Increased inflammatory response contributes to the early brain injury and delayed vasospasm after SAH. Moreover, we found that the inflammatory response could be induced and amplified following recombinant HMGB1 (rHMGB1) addition in cultured neurons. Based on the latest researches in this field, we raised a hypothesis that HMGB1, a prototypical member of damage-associated molecular pattern (DAMP) family, could be passively released from the damaged neuroglia cells and hemotocyte lysis after SAH. Extracellular HMGB1 initiated the inflammation through its receptors. The inflammatory mediators then acted on the neurocytes to make them actively release HMGB1 continuously, manifesting an double phases. HMGB1 might be the key factor to induce sterile inflammation, and thus be one of the origin of early brain injury and delayed vasospasm after SAH. Inhibition of extracellular HMGB1 activities might be a novel therapeutic target for SAH to reduce the damaging inflammatory response. Glycyrrhizic acid (GA) which was extracted from liquorice and confirmed as a nature inhibitor of HMGB1 with little side-effects could inhibit extracellular HMGB1 cytokine activities and reduce the level of inflammatory response, thus alleviating early brain injury and cerebrovasospasm. GA might be a new novel therapy of SAH for better outcomes.     

Hypocalcaemia may reduce the beneficial effect of magnesium treatment in aneurysmal subarachnoid haemorrhage.

To assess whether magnesium treatment in patients with subarachnoid haemorrhage (SAH) is associated with hypocalcaemia and whether hypocalcaemia in these patients is associated with an increased risk of delayed cerebral ischemia (DCI) and poor outcome. All 137 patients randomized in the clinically controlled "Magnesium in Aneurysmal Subarachnoid Haemorrhage" trial were included. The relationship between mean serum magnesium and mean serum calcium during treatment was assessed with linear regression. The relationship between hypocalcaemia (serum calcium < 2.0 mmol/L) during treatment and the occurrence of DCI and poor outcome was studied with the Cox proportional hazards method and logistic regression, respectively. There was a statistically significant inverse relation between elevated serum magnesium and hypocalcaemia (B = -0.27; 95% CI, -0.33 to -0.20; p < 0.001). Patients with hypocalcaemia during study treatment had an increased frequency of DCI (HR 2.1; 95% CI, 1.0 to 4.3), and an increased risk for poor outcome (OR 2.9; 95% CI, 1.4 to 6.4), but this effect attenuated in the multivariable analysis (OR 1.9; 95% CI, 0.8 to 4.7). In conclusion, prolonged elevated serum magnesium is associated with hypocalcaemia. Hypocalcaemia is associated with an increased risk of DCI and poor outcome and may therefore reduce the potential beneficial effect of magnesium treatment in SAH.     

颅脑外伤后并发低钠血症的危险因素分析

目的探讨颅脑外伤患者并发低钠血症的发生机制及危险因素,以期为其早期预测及预防提供参考。方法回顾性分析2016年6月至2019年6月我院收治的185例中型和重型颅脑外伤患者的临床资料,包括导致低钠血症的不同病因、损伤类型、性别、格拉斯哥昏迷(GCS)评分、手术、脑水肿、颅底骨折和穿透性性损伤等;采用单因素χ^2检验和多因素Logistic回归分析探究颅脑外伤后并发低钠血症的危险因素。结果所有患者中,80例出现低钠血症,其中钠盐摄入不足、利尿剂过量使用47例,抗利尿激素分泌失调综合征19例,脑性耗盐综合征14例。低钠血症更多发生在脑挫裂伤、蛛网膜下腔出血和弥漫性轴索损伤患者中,差异具有统计学意义(P<0.05)。单因素χ^2检验结果显示,GCS评分(P=0.000)、脑水肿(P=0.000)、颅底骨折(P=0.000)、穿透性损伤(P=0.001)是颅脑外伤后并发低钠血症的相关因素。多因素Logistic回归分析结果显示,GCS评分(P=0.006)、脑水肿(P=0.006)、颅底骨折(P=0.000)、穿透性损伤(P=0.015)是颅脑外伤后并发低钠血症的危险因素。结论脑挫裂伤、蛛网膜下腔出血、弥漫性轴索损伤、GCS评分≤8分、脑水肿、颅底骨折和穿透性损伤的颅脑外伤患者更易发生低钠血症,应早期关注患者血清钠水平,明确病因及时纠正,防止病情恶化。