Rho激酶、氧合血红蛋白与蛛网膜下腔出血后脑血管痉挛的关系

目的探讨Rho激酶、氧合血红蛋白在蛛网膜下腔出血后患者脑脊液中的表达与浓度及其在脑血管痉挛的调控作用。方法采集62例蛛网膜下腔出血患者入院后第1、3、7、10、14 d脑脊液标本,RT-PCR方法检测Rho激酶mRNA的表达,采用比色法测定脑脊液中氧合血红蛋白的浓度,采用TCD检测颅内主要动脉血流速度。结果出血后第3 d脑脊液中Rho激酶表达及氧合血红蛋白浓度增高,在出血后第7 d达到高峰,而后逐渐下降。结论蛛网膜下腔出血患者脑脊液中Rho激酶的表达与氧合血红蛋白浓度有关,参与蛛网膜下腔出血后脑血管痉挛的发生,其含量与脑血管痉挛程度相关。     

蛛网膜下腔出血腰池持续引流前后脑脊液中NO浓度的变化

目的 探讨腰池持续引流防治脑血管痉挛的效果及其对脑脊液中一氧化氮（NO）浓度的影响。方法 50例破裂动脉瘤蛛网膜下腔出血患，随机分为引流组25例。对照组25例。引流组在电解可脱弹簧圈（GDC）栓塞术后立即实施腰池持续引流，对照组行间断腰椎穿刺。脑脊液NO浓度采用镉粒子还原法测定。结果 引流组中发生症状性脑血管痉挛2例。对照组7例。血管痉挛患的NO浓度明显降低，引流组脑脊液中NO浓度在出血后第5d起明显高于对照组。结论 腰池持续引流可有效清除蛛网膜下腔积血，提高脑脊液中NO的浓度。     

纤维蛋白原动态变化与蛛网膜下腔出血后脑血管痉挛的相关性

目的 :研究蛛网膜下腔出血后脑血管痉挛患者纤维蛋白原 (Fb G)动态变化及其对蛛网膜下腔出血后脑血管痉挛的预测价值。方法 :对发病 2 4小时内入院的蛛网膜下腔出血患者发病后 1d及 3d,7d,14d,2 1d外周血 Fb G动态观察 ,比较 32例蛛网膜下腔出血后脑血管痉挛患者与无脑血管痉挛的蛛网膜下腔出血患者 Fb G动态变化。结果 :无脑血管痉挛的蛛网膜下腔出血患者发病后 7d Fb G明显升高 (P<0 .0 0 1) ,14d恢复正常 (P>0 .0 5 ) ,2 1d时低于正常 (P<0 .0 0 1) ;出现脑血管痉挛的患者发病后 3d,7d,14d Fb G均明显升高 (P<0 .0 0 1) ,2 1d时恢复正常 (P>0 .0 5 ) ,且发病后3d,7d,14d,2 1d Fb G均明显高于无脑血管痉挛发生的患者 (P<0 .0 1)。结论 :蛛网膜下腔出血患者 Fb G一过性升高 ,并发脑血管痉挛者更明显 ,动态观察 Fb G变化可预测脑血管痉挛的发生。     

动脉瘤夹闭术对不同Fisher分级患者的蛛网膜下腔积血量及脑血管痉挛程度的影响

目的探讨动脉瘤夹闭术对不同Fisher分级患者的蛛网膜下腔积血量和脑血管痉挛程度的影响。方法选取我院2008-06—2014-11 90例动脉瘤性蛛网膜下腔出血患者为研究对象,依据不同Fisher分级分为FisherⅠ组、FisherⅡ组和FisherⅢ组,选取同期30例未破裂动脉瘤性蛛网膜下腔出血患者为对照组,观察患者术后血量和脑血管痉挛程度状况。结果FisherⅢ组第3天和第7天及第13天氧合血红蛋白含量、大脑中动脉血流速度明显的高于FisherⅠ组、FisherⅡ组,且FisherⅡ组和FisherⅢ组氧合血红蛋白含量、大脑中动脉血流速度均明显的高于对照组,差异有统计学意义(P0.05)。结论临床中FisherⅠ级和FisherⅡ级动脉瘤性蛛网膜下腔出血患者行动脉瘤夹闭术后积血量会增加,加重血管痉挛。而FisherⅢ分级动脉瘤性蛛网膜下腔出血患者行动脉瘤夹闭术后血量降低,减轻脑血管痉挛。     

尼莫地平加脑脊液置换治疗蛛网膜下腔出血的预后

目的观察钙离子拮抗剂尼莫地平加脑脊液置换对蛛网膜下腔出血的临床预后。方法 74例蛛网膜下腔出血患者分为治疗组38例和照组36例。2组入院后即开始泵入尼莫地平,持续14d;治疗组加脑脊液置换治疗,其他治疗同对照组。观察2组的脑血管痉挛发生率及临床预后。结果治疗组脑血管痉挛及临床预后均较对照组显著好转(P<0.05)。结论尼莫地平加脑脊液置换治疗蛛网膜下腔出血可以有效减少脑血管痉挛及改善预后。     

蛛网膜下腔出血后脑血管痉挛患者纤维蛋白原的动态变化意义

目的 研究蛛网膜下腔出血后脑血管痉挛患者纤维蛋白原(FbG)的动态变化及其对蛛网膜下腔出血后脑血管痉挛的预测价值.方法 对经CT诊断发病24h内入院的蛛网膜下腔出血患者,动态观察发病后ld、3d、7d、14d及21d外周血FbG,比较41例蛛网膜下腔出血后脑血管痉挛患者与23例无脑血管痉挛的蛛网膜下腔出血患者的FbG动态变化.结果 出现脑血管痉挛的患者发病后3d、7d、14d FbG均明显升高(P＜0.001),21d时恢复正常(P＞0.05),且发病后3d、7d、14d、2ld FbG均显著高于无脑血管痉挛发生的患者(P＜0.01);无脑血管痉挛的蛛网膜下腔出血患者发病后7d FbG明显升高(P＜0.001),14d恢复正常(P＞0.05),21d时低于正常(P＜0.001).结论 动态检测血浆FbG水平,对蛛网膜下腔出血后脑血管痉挛的早期发现、早期治疗,减少脑血管痉挛的发生,具有重要的临床意义.     

阿托伐他汀钙对动脉瘤性蛛网膜下腔出血后脑血管痉挛的作用及机制

目的研究阿托伐他汀钙对动脉瘤性蛛网膜下腔出血(a SAH)后血管痉挛(CVS)的影响及机制。方法连续收集2013年03月至2015年11月收治的动脉瘤性蛛网膜下腔出血患者共62例,随机分为研究组(33例)与对照组(29例)。对照组给予常规治疗,研究组在对照组治疗基础上加服阿托伐他汀钙(20 mg/qn,连服14 d)。于发病后第1天、第3天、第7天和第14天检测分析两组患者大脑中动脉平均血流速度(VMCA)及血清中内皮素血管肽-1(ET-1)、一氧化氮(NO)水平。同时,比较两组患者脑血管痉挛(CVS)的发生率、迟发型脑梗死和复发出血的发生率以及Modified Rankin Scale score量表(mRS)评分。结果在第7天、第14天研究组的VMCA、ET-1均低于对照组,差异有统计学意义(P0.05)。在第3天、第7天、第14天,研究组NO含量高于对照组,差异有统计学意义(P0.05)。研究组脑血管痉挛的发生率较对照组低(36.36%vs.65.52%),差异有统计学意义(P0.05)。研究组mRS评分≤2分所占比例较对照组高(75.76%vs.44.83%),差异有统计学意义(P0.05)。迟发型脑梗死和再发出血的发生率两组差异无统计学意义(P0.05)。结论阿托伐他汀钙能够减少蛛网膜下腔出血后脑血管痉挛的发生,并促进神经功能恢复,其机制可能与改善血管内皮舒缩功能有关。     

动脉瘤性SAH后症状性脑血管痉挛与高凝状态相关性及防治研究

目的:探讨动脉瘤性SAH后症状性脑血管痉挛与病人外周血清高凝状态的相关性,同时观察应用丹参注射液对血液高凝状态的影响。方法:60例动脉瘤性蛛网膜下腔出血(SAH)病人,出现症状性脑血管痉挛38例,症状性脑血管痉挛组随机分为丹参治疗组和非丹参治疗组。所有病人分别在住院时、3天、7天、14天、21天,进行周围血中FDP和D-dimer含量的测定并进行动态观察。结果:症状性脑血管痉挛组病人FDP和D-dimer的含量在住院后各时间段明显高于非症状性脑血管痉挛组(P<0.01),住院后第14天、21天丹参治疗组FDP和D-dimer的含量明显低于非丹参治疗组(P<0.05)。症状性脑血管痉挛组中,丹参治疗组病人的预后明显优于非丹参治疗组。结论:动脉瘤性SAH引起症状性脑血管痉挛与血粘稠度增高有明显关系。丹参注射液可明显降低血粘稠度,促进脑血液循环对改善症状性脑血管痉挛的脑缺血症状有明显的治疗作用。     

蛛网膜下腔出血性脑血管痉挛动物模型的制作

蛛网膜下腔出血引起的脑血管痉挛是导致蛛网膜下腔出血患者不良预后的主要原因之一,其发生机制至今尚未完全明了。因此,建立一种理想的蛛网膜下腔出血性脑血管痉挛动物模型将对脑血管痉挛发生机制及临床防治的研究起到巨大的推动作用。文章介绍了各种蛛网膜下腔出血性脑血管痉挛动物模型的制作方法、优缺点及应用范围,但目前尚无一种用于研究蛛网膜下腔出血后症状性脑血管痉挛的理想模型。     

脑血管痉挛活体动物模型的研究进展

蛛网膜下腔出血引起的脑血管痉挛是导致蛛网膜下腔出血患者不良预后的主要原因之一,其发生机制至今尚未完全明了。因此,寻找一种理想的蛛网膜下腔出血后脑血管痉挛动物模型将对脑血管痉挛发生机制及临床防治的研究起到巨大的推动作用,但目前尚无一种用于研究蛛网膜下腔出血后症状性脑血管痉挛的理想模型。本文就应用各种动物制作脑血管痉挛模型的研究进展进行综述。     

17β-雌二醇对蛛网膜下腔出血脑血管痉挛的疗效与其可能机制

性别的差异是否影响颅内动脉瘤破裂所引发蛛网膜下腔出血后的预后,仍未有定论,雌性素对于血管扩张的可能作用也尚未确定。本研究评估17β-雌二醇（estradiol,E2）在大鼠两次出血的蛛网膜下腔出血动物模型中,对于蛛网膜下腔出血引发的脑血管痉挛的治疗效果与可能机制。方法 以0.3 mg/ml E2混合玉米油填充于30 mm长的硅胶管（Silastic tube）,于雄性大鼠引发蛛网膜下腔出血后1 h,包埋于动物皮下。测量包埋的第0、1、2、3、4及7天大鼠血中E2浓度。脑血管痉挛的程度以第一次出血后7天的基底动脉横切面平均面积来评估。同时检查基底动脉内皮型一氧化氮合酶（endothelial nitric oxide synthase,eNOS）及诱导型一氧化氮合酶（Inducible nitric oxide synthase,iNOS）的表现。结果 以E2治疗大鼠的血中浓度维持在生理浓度（56～92 pg/ml）,与给予赋形药物的溶剂对照组相比较,研究组E2浓度的增加有统计学上的意义。E2治疗能有意义的减少蛛网膜下腔出血引发的脑血管痉挛（P <0.01）。E2治疗能有意义的减少脑血管痉挛后基底动脉iNOS-mRNA及蛋白质的表达增加,而对照组无此作用。脑血管痉挛后eNOS-mRNA及蛋白质的表达受压抑,但可经E2治疗而减缓。结论 建议持续性给予E2,维持其于生理浓度,可防止蛛网膜下腔出血后的脑血管痉挛,E2防止蛛网膜下腔出血后脑血管痉挛的效益,部分与E2可防止蛛网膜下腔出血后iNOS的表达及保留eNOS的表达有关。因此,E2对于治疗蛛网膜下腔出血后的脑血管痉挛是一种值得进一步探讨的方法。     

蛛网膜下腔出血后脑血管痉挛与血管活性物质的关系

目的 探讨蛛网膜下腔出血后脑血管痉挛与血管活性物质的关系。方法 测定52例蛛网膜下腔出血患者血浆血栓素B_2(thromboxane B_2,TXB_2)、6-酮-前列环素F1α(6-keto-prostaglandin,6-Keto)及血浆和脑脊液中血管紧张素转化酶(angiotensin converting enzyme,ACE)活性,同时通过经颅多普勒超声检查法(transcranial Doppler nltrasonography,TCD)观察蛛网膜下腔出血后脑血管平均血流速度(Vm)的变化,并与正常对照组进行比较。结果 蛛网膜下腔出血患者血浆TXB_2水平高于对照组(P<0.01),6-Keto水平低于对照组(P<0.05或P<0.01);发病后血浆ACE活性无明显改变,但脑脊液中ACE活性高于对照组(P<0.01);大脑中动脉平均血流速度于蛛网膜下腔出血后第4～5d的变化最为显著(P<0.01)。结论 蛛网膜下腔出血后患者血浆TXB_2、6-Keto与脑脊液ACE水平均发生明显变化,结合TCD检测结果,推测蛛网膜下腔出血后脑血管痉挛与血管活性物质水平有关。     

Bilirubin production and oxidation in CSF of patients with cerebral vasospasm after subarachnoid hemorrhage.

Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) remains a significant cause of mortality and morbidity; however, the etiology is, as yet, unknown, despite intensive research efforts. Research in this laboratory indicates that bilirubin and oxidative stress may be responsible by leading to formation of bilirubin oxidation products (BOXes), so we investigated changes in bilirubin concentration and oxidative stress in vitro, and in cerebral spinal fluid (CSF) from SAH patients. Non-SAH CSF, a source of heme oxygenase I (HO-1), and blood were incubated, and in vitro bilirubin production measured. Cerebrospinal fluid from SAH patients was collected, categorized using stimulation of vascular smooth muscle metabolism in vitro, and information obtained regarding occurrence of vasospasm in the patients. Cerebral spinal fluid was analyzed for hemoglobin, total protein and bilirubin, BOXes, malonyldialdehyde and peroxidized lipids (indicators of an oxidizing environment), and HO-1 concentration. The formation of bilirubin in vitro requires that CSF is present, as well as whole, non-anti-coagulated blood. Bilirubin, BOXes, HO-1, and peroxidized lipid content were significantly higher in CSF from SAH patients with vasospasm, compared with nonvasospasm SAH CSF, and correlated with occurrence of vasospasm. We conclude that vasospasm may be more likely in patients with elevated BOXes. The conditions necessary for the formation of BOXes are indeed present in CSF from SAH patients with vasospasm, but not CSF from SAH patients without vasospasm.     

Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after aneurysmal subarachnoid hemorrhage and measurement of biomarkers

Cisternal irrigation with thrombolytic agents was used to prevent post-SAH vasospasm, but its role remained inconclusive. To verify effectiveness of papaverine (PPV) in preventing vasospasm, we studied relationship between inflammatory biologic markers and vasospasm. This prospective study included 121 patients with clipped anterior circulation aneurysms that had ruptured, and 372 control patients. Patients were divided into three groups according to cisternal irrigation method: simple drain, papaverine group, and urokinase (UK) group. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV group showed similar incidence of vasospasm with UK group, but lower incidence than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly higher in the SAH group than in the control group. CSF and serum levels were more elevated on day 7 than day 3, and the degree of elevation were more marked when measured in the CSF than in the serum. However, there was no statistical difference between measured levels of ICAM-1 and VCAM-1, and vasospasm development. PPV cisternal irrigation was similarly effective as UK at preventing vasospasm. Although neither PPV nor UK irrigation could reduce the concentration of adhesion molecules compared with simple drain, we found levels of ICAM-1 and VCAM-1 were specifically elevated in the CSF. Therefore, further research should focus on anti-inflammation as a therapeutic target against cerebral vasospasm and on the CSF as the optimum place where such inflammatory action practically brought about.     

Determination of cerebrospinal fluid concentrations of arginine and dimethylarginines in patients with subarachnoid haemorrhage

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric dimethylarginine (SDMA) are very sparse in humans. We here present a new hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS) method for the precise determination of these substances in CSF. The method requires only minimal sample preparation and features isotope labeled internal standards. First data of patients with SAH showed that on the day of admission CSF concentration values of L-arginine and ADMA were not significantly different from controls, but increased markedly during the course of the hospital stay. The decrease of the L-arginine to ADMA ratio points to a progressive impairment of the NO production rate in the brain after SAH which is confirmed by a simultaneous decrease in nitrate and nitrite concentrations in CSF.     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage.

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.     

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p < 0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p < 0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.