阻滞脑淋巴引流加重蛛网膜下腔出血继发性脑损伤的实验研究

目的 探讨脑淋巴引流途径在蛛网膜下腔出血(SAH)继发性脑损伤中的作用.方法 将大鼠分为对照组、SAH组、SAH+脑淋巴引流阻滞(CLB)组.监测血气、血压和颅内压,3 d后观察脑实质局部脑血流量(rCBF),检测大脑皮层细胞凋亡、caspase-3 mRNA和caspase-3表达.结果 SAH组颅内压急剧升高,SAH+CLB组颅内压升高更显著;SAH后rCBF降低,CLB加重rCBF下降;SAH后大脑皮层有较多凋亡细胞,SAH+CLB组细胞凋亡更严重;SAH组大脑皮层caspase-3 mRNA和caspase-3表达增加,SAH+CLB组caspase-3 mRNA和caspase-3表达进一步增强.结论 脑淋巴引流途径阻滞可加重SAH继发性脑损伤,该途径在SAH时可能起到内源性保护作用.     

内皮素-1在动脉瘤性蛛网膜下腔出血病人血管痉挛中的作用

脑血管痉挛是动脉瘤性蛛网膜下腔出血(SAH)病人死亡的主要原因之一。约有60%的SAH 病人发生脑血管痉挛。痉挛多在出血后4～10天出现,持续2～3周,可引起短暂性或持久性神经系统损害。目前,其病因及发病机理仍不明确。近年来,对源于血管内皮的血管收缩肽内皮素-1在SAH 后血液、脑脊液(CSF)水平的作用已引起重视。     

川芎嗪对实验性SAH后CVS防治作用的研究

目的研究兔症状性蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)与内皮素(ET)和一氧化氮(NO)的关系及川芎嗪的保护作用.方法采用双侧颈动脉结扎和枕大池二次注血制成兔SAH模型,观察SAH前后动物进食量和神经功能改变,用放射免疫方法和硝酸还原酶法分别测定血液和脑脊液中ET和NOx-含量,以氢清除法测定局部脑血流量(rCBF).结果SAH后大部分动物进食量有不同程度的下降,所有动物均有不同程度的神经功能障碍和rCBF下降.SAH后血液和脑脊液中ET含量增加,NOx-含量下降(P＜0.01).上述变化随出血时间延长和出血量的增大而增加.川芎嗪治疗组上述变化均有不同程度的改善.结论双侧颈动脉结扎后枕大池二次注血可制成可靠的兔症状性SAH后CVS的动物模型.兔SAH后ET和NO含量的改变与CVS的发生密切相关,并进而导致临床症状的恶化.川芎嗪可通过抑制SAH后ET和NO的变化而对CVS的发生和发展起到防治作用.     

一种新的蛛网膜下腔出血（SAH）动物模型的建立

利用大鼠经额钻孔,将导管插至颅底动脉环,直接注血模拟临床常见的动脉瘤出血,动态观测局部脑血流(rCBF)变化。结果发现:在造成 SAH 后,插管侧半球的 rCBF 急剧下降,最大下降幅度为60.8%;对侧半球的 rCBF 在 SAH 后20分钟也开始降低,血流最大下降幅度为66.8%;半球低 rCBF 情况持续48小时以上。SAH 急性期血气及血压动态观察结果平稳。     

蛛网膜下腔出血诱导脑血管病理改变的研究进展

蛛网膜下腔出血(subarachnoid hemorrhage,SAH)占所有卒中患者的6%～8%.动脉瘤破裂是其主要原因,25%患者会在24 h内死亡,出血后1个月内死亡率上升到40%～60%,总体死亡率约为50%[1].约70%的幸存者在出血后4～7 d出现脑实质外大血管迟发性脑血管痉挛,由其引起的死亡率甚至超过动脉瘤破裂及再出血本身引起的死亡率.其中40%患者的脑血管痉挛是无症状性的,然而30%患者会遗留严重的认知功能障碍和局灶性神经功能障碍[2].     

大鼠蛛网膜下腔出血后早期脑损伤模型的建立

目的 建立一种微创、重复性好的大鼠蛛网膜下腔出血后早期脑损伤动物模型.方法 采用视交叉前池注血法建立蛛网膜下腔出血( SAH)后早期脑损伤(EBI)动物模型.在脑立体定位仪引导下将导管插入视交叉前池,注入300μl自体动脉血建立SAH后EBI模型.进行神经功能学评分,采用激光多普勒血流量仪(LDF)测定局部脑血流量(rCBF),解剖观察前循环周围血液分布情况,应用透射电子显微镜观察海马区神经细胞超微结构变化.结果 大部分大鼠在SAH后有神经行为学异常,48 h后逐渐恢复正常.SAH后不同时间点的rCBF均低于对照组.模型组大鼠颅脑解剖发现前循环蛛网膜下腔有大量的血液和血凝块.透射电子显微镜观察:与对照组比较,SAH组神经细胞线粒体和内质网肿胀,核染色质凝聚、趋边.结论 此动物模型稳定可靠,重复性高,适合进行临床前循环动脉瘤性蛛网膜下腔出血后早期脑损伤病理生理研究.     

巴曲酶对大鼠SAH后迟发性脑血管痉挛细胞凋亡的影响

目的　探讨巴曲酶防治蛛网膜下腔出血 (SAH)迟发性脑血管痉挛 (DCVS)及细胞凋亡的作用。方法　“枕大池二次注血法”建立大鼠SAH DCVS动物模型 ,采用TUNEL法和流式细胞仪动态观察巴曲酶对大鼠SAH DCVS的血管内皮细胞、平滑肌细胞及神经细胞凋亡的影响。结果　TUNEL检测发现巴曲酶组在SAH后 3d、7d血管内皮细胞、平滑肌细胞及神经细胞凋亡数均明显低于同期单纯注血组 ;流式细胞仪检测亦发现巴曲酶组凋亡率明显降低 ,与相对应单纯注血组比较均有明显差异 (P <0 .0 0 1)。结论　巴曲酶可以抑制SAH后的细胞凋亡 ;防治SAH DCVS及其所致的迟发性脑缺血、迟发性神经元损伤。     

蛛网膜下腔出血后迟发性脑血管痉挛并脑梗塞的临床与CT分析

目的　探讨蛛网膜下腔出血 (SAH)合并脑梗塞的临床表现、CT所见及其与迟发性脑血管痉挛(DCVS)的关系。　　方法　对 9例SAH后DCVS并脑梗塞患者的临床和CT资料进行分析。　　结果　CT表现分三类 :1 大脑前动脉支配区双侧或额叶梗塞。 2 大脑中动脉支配区外侧裂附近颞顶叶梗塞。 3 多发性脑内或底节区梗塞。临床上常见于Ⅳ～Ⅴ级的患者 ,多有SAH再发出血、去脑强直或抽搐发作 ,意识障碍时间较长及迟发性脑缺血性神经功能障碍 (DIND)。　　结论　提示较严重的DCVS可能增加SAH后脑缺血性损伤的发生。但是 ,SAH并脑梗塞的发生常是多种因素引起的复杂的病理过程。     

尼莫地平减轻蛛网膜下腔出血后脑损伤

目的 探讨尼莫地平对蛛网膜下腔出血(SAH)后脑损伤的防治作用。方法 用血管内穿刺法制作大鼠SAH模型。对SAH组和尼莫地平处理组观察24h内局部脑血流量(rCBF)和脑组织水、电解质含量的动态变化。结果 SAH后rCBF迅速降低，1h达最低值，24h内持续于低水平状态。SAH后6h、24h脑组织含水率和Na^ 含量明显增加，K^ 含量减低；脑组织Ca^2 含量在SAH后1h开始显著增加。尼莫地平对上述的指标均有改善作用。结论 尼莫地平可减轻实验性SAH后脑损伤。     

血浆脑利钠肽与蛛网膜下腔出血后脑血管痉挛及低钠血症的关系

目的　探讨血浆脑利钠肽(BNP)与蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)及低钠血症的关系。方法　动态测定30例SAH患者发病后1~3d、4~6d、7~9d及10~12d4个时段的血浆BNP和血钠水平,对血浆BNP和血钠水平进行相关性分析;比较有无CVS及有症状与无症状CVS患者的血浆BNP水平。同时检测18名健康人的血浆BNP水平作为对照。结果　SAH患者血浆BNP水平明显高于对照组(P<0. 01),虽然无CVS及无症状CVS患者血浆BNP水平在SAH后4个时段中逐渐下降,但有症状CVS患者第3时段血浆BNP水平明显高于第1时段(P<0. 01 );第2 ~4时段血钠与血BNP水平呈显著负相关(r2 =-0 .763,r3 =-0 .681,r4 =-0 .764,均P<0 .01)。结论　BNP可能导致和参与了SAH后CVS及低钠血症的发生,并在SAH后CVS的发病机制中起重要的作用。     

Nimodipine Attenuation of Early Brain Dysfunctions Is Partially Related to its Inverting Acute Vasospasm in a Cisterna Magna Subarachnoid Hemorrhage (SAH) Model in Rats

ABSTRACT Subarachnoid hemorrhage (SAH)-induced brain injury is highly related to neurological deficits and mortality. Regional cerebral blood flow (rCBF) changes and vasoconstriction are two complications that occur soon after SAH experimentally. In this study we investigated the changes in rCBF and vertebro-basilar arterial diameter in a cisterna megna SAH model in Sprague-Dawley rats and intended to explore whether improving early rCBF reduction and cerebral vasospasm could contribute to alleviating blood-brain barrier (BBB) dysfunction. In rats for rCBF, vasospasm and BBB permeability assessments, nimodipine (NDP) or saline was administered intravenously 5 minutes after SAH. rCBF within the first 60 minutes after SAH was measured by laser Doppler flowmetry. BBB permeability indexed by Evans Blue extravasation was assessed 4?hours after SAH. Angiography for the caliber changes of the vertebro-basilar artery were conducted 30 minutes post SAH. Pronounced rCBF reduction and vasospasm were observed soon after SAH, followed by BBB permeability increment. NDP administration could improve rCBF and attenuate vasospasm, followed by the alleviation of BBB permeability. Our results demonstrate that early improvement of cerebral circulation by NDP may contribute to the reduction in brain injury indexed by BBB disruption.     

Effects of hyperoxia, glycerol and ventricular drainage on ICP and CBF in patients with increased ICP due to CSF circulatory-absorbance disturbance

The effects of hyperoxia, glycerol and ventricular drainage on intracranial pressure (ICP) and cerebral blood flow (CBF) were studied in cases with cerebrospinal fluid (CSF) circulatory-absorbance disturbance due to subarachnoid hemorrhage (SAH) or intraventricular hematoma. Ventricular fluid pressure (VFP) was monitored through a controlled ventricular drainage (CVD) tube using a Statham P-50 pressure transducer. CBF was measured by the 10mCi133Xe intravenous injection method using a Valmet BI-1400 rCBF analyzer. ISI (initial slope index) was used for the CBF value. Studied cases were 19 SAH patients and 2 hypertensive intracerebral hematoma cases with intraventricular hematoma. Hyperoxia included hyperbaric oxygen (HBO), reduced ICP and CBF. During pure oxygen inhalation at atmospheric pressure (1ATA . O2), there was a tendency toward a relationship showing that the higher the resting state ICP, the lesser the likelihood of a CBF decrease. This may indicate that increased ICP impairs cerebral vascular reactivity to hyperoxia in relation to the degree of elevation. The effects of hyperoxia on ICP and CBF were temporary and they promptly returned to the resting state after cessation of oxygen inhalation. In some cases, there was a rebound phenomenon in ICP after HBO. Glycerol administration reduced ICP and increased CBF. There was no clear correlation between resting state ICP and CBF increase after glycerol administration. The effects of glycerol were also temporary. ICP control by opening CVD increased CBF. There was a correlation between the level of resting state ICP and the CBF increase after the opening of CVD. In cases with CSF circulatory-absorbance disturbance, elevated ICP reduced CBF and may further worsen the cerebral damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

动物蛛网膜下腔出血后脑血管痉挛与内皮素、一氧化氮的关系

目的:研究兔症状性蛛网膜下腔出血(ＳＡＨ)后脑血管痉挛(ＣＶＳ)与内皮素(ＥＴ)和一氧化氮(ＮＯ)的关系。方法:采用兔ＳＡＨ模型,观察ＳＡＨ前后动物进食量、神经功能和局部脑血流量(ｒＣＢＦ)改变,测定血液和脑脊液中ＥＴ和ＮＯｘ－含量。结果:ＳＡＨ后动物进食量和ｒＣＢＦ下降、神经功能障碍,血液和脑脊液中ＥＴ含量增加,ＮＯｘ－含量下降(Ｐ＜０．０１)。结论:兔双侧颈动脉结扎后枕大池二次注血可制成可靠的症状性ＳＡＨ后ＣＶＳ模型。ＳＡＨ后ＥＴ和ＮＯ含量的改变与ＣＶＳ的发生密切相关,并进而导致临床症状的恶化。     

Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). METHODS: In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. RESULTS: Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. CONCLUSIONS: In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.     

Cerebral edema leading to decompressive craniectomy: an assessment of the preceding clinical and neuromonitoring trends

The aim of this study was to examine the pre-operative clinical and neuromonitoring courses in patients with a decompressive craniectomy to assess and to compare clinical and neuromonitoring signs indicating extensive cerebral edema. We conducted a retrospective analysis of the clinical signs and courses of simultaneous monitoring of intracranial pressure (ICP) and cerebral oxygenation (PtiO2) in 26 consecutive patients who were sedated and treated with a decompressive craniectomy due to extensive cerebral edema after aneurysmal subarachnoid hemorrhage (SAH) (n = 20) or severe head injury (SHI) (n = 6). Pathological monitoring trends always preceded clinical deterioration. In 18 of 26 patients extensive cerebral edema was indicated solely by increasing ICP > 20 mmHg or decreasing PtiO2 < 10 mmHg or both. Anisocoria occurred in only 8 of 26 patients. As opposed to SHI patients, 9 of 20 SAH patients showed decreasing PtiO2 as first warning sign clearly before neurological deterioration or ICP increase. This series shows the utility of combined ICP and PtiO2 monitoring in patients who develop extensive cerebral edema. Pathological monitoring trends indicate deterioration prior to clinical signs which offers a wider therapeutical window. PtiO2 monitoring appears to be particularly valuable after aneurysmal SAH as adjunct to ICP monitoring and CT imaging.     

Noninvasive measurement of cerebral vasopasm in patients with subarachnoid hemorrhage

Regional cerebral blood flow (rCBF) was measured as fast flow clearance (F1) and the initial slope index (ISI2) after inhalation of 133Xe in 30 patients with subarachnoid hemorrhage (SAH). Vasomotor responsiveness to reduction in end-tibal PECO2 was examined in those patients who could carry out this procedure satisfactorily as a test for the presence or absence of vasospasm. F1 and ISI2 were significantly reduced in patients with recent SAH compared to 35 age-matched normal volunteers. The degree of reduction of F1 and ISI2 correlated directly with severity of the neurological deficit graded according to the Hunt and Hess rating scale. Topographic reductions of rCBF correlated with angiographically demonstrated vasospasm or intracerebral hematoma. The degree of impairment of cerebral vasomotor responsiveness to reduction of PECO2 by hyperventilation also correlated with the severity of vasospasm demonstrated angiographically in 16 patients. The reductions of rCBF values were maximal during the first week after SAH but returned gradually toward normal by the 5th week. Individual patients with SAH whose lowest F1 values were above 50 ml/100 g brain/min tolerated surgical intervention best. Non-invasive measurements of rCBF after SAH appear to be helpful in estimating the presence and time course of vasospasm, in recognizing the development of normal pressure hydrocephalus, and in planning medical and surgical management.     

Cerebral energy failure after subarachnoid hemorrhage: the role of relative hyperglycolysis.

After subarachnoid hemorrhage (SAH) cerebral metabolism is significantly impaired. Hyperglycolysis describes the reduction of oxidative metabolism followed by a relative increase of anaerobic glycolysis to maintain energy supply. This phenomenon is known in head injury but has not as yet been shown after SAH. This study was conducted to test the hypothesis that hyperglycolysis is present in SAH patients and is associated with vasospasm. A total of 105 measurements were conducted on 21 SAH patients (age 49+/-15 years, median World Federation of Neurosurgical Societies Grade 4) over the first 5 days following admission. Arteriovenous differences were calculated for oxygen (avDO2) and glucose (avDGlc). Relative hyperglycolysis was defined as metabolic ratio (MR=avDO2[mmol/L]/avDGlc[mmol/L])<3.44. Jugular-venous saturation for oxygen (SjvO2), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) were monitored. Relative hyperglycolyis was recorded in 34% of studies after SAH. In hyperglycolytic studies both jugular-venous lactate and SjvO2 were significantly elevated (jugular-venous lactate 14.9+/-9.9 vs. 11.8+/-5.5 mg/dL, p=0.04; SjvO2: 70.0+/-18% vs. 81.7+/-9%, p=0.002). Relative hyperglycolysis is associated with outcome after SAH. In patients who died after SAH almost 50% of studies showed hyperglycolysis, whereas patients who survived without neurological deficit had no hyperglycolytic events. Relative hyperglycolysis is a common event after SAH. It may be associated with relative hyperemia but most importantly with outcome.     

鼠脑血管痉挛时尼莫地平对体感诱发电位的影响

目的 探讨蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）对体感诱发电位（SEP）的影响,及尼莫地平（ND）的保护作用。方法 对单纯SAH组和ND处理组大鼠观察手术前后基底动脉管径,并检测24h内局部脑血流量（rCBF)、SEP潜伏期及脑组织内皮素-1（ET-1）含量的动态变化。结果 SAH组大鼠在诱导SAH后rCBF立即降低,并持续24h,同时有基底动脉痉挛;SAH后1h开始至24hSEP潜伏期逐渐延长,脑组织ET-1含量显著增加,ND处理组大鼠上述变化均较轻。结论 SAH后CVS可通过脑血流的降低,脑组织ET-1增加而导致SEP潜伏期延长,ND通过拮抗脑组织ET-1变化而对之具有保护作用。     

Effects of the cortical subarachnoid hemorrhage on cerebral glucose metabolism

Neurological deficits following human subarachnoid hemorrhage (SAH) have been related to the cerebral arterial spasm and the increase in intracranial pressure (ICP) secondary to the development of hydrocephalus. Metabolic depression in experiment study was thought as resulting from brain stem dysfunction. On the other hand, some reports have shown no relationship between vasospasm and neurological abnormalities. The mechanism of cerebral metabolism depression after SAH remains unclear. The effect of blood in the cortical subarachnoid space on the cerebral metabolism has not been known well. To investigate this effect, a new cortical SAH model was developed using rat and local cerebral glucose utilization (LCGU) after production of SAH was measured. A cortical SAH model: a small burr hole was made on the left parietal bone and the arachnoid membrane was pierced with a tapered glass-needle 60 mu tip in diameter. Fresh autologous non-heparinized arterial blood 0.04 ml was injected into subarachnoid space within 60 seconds through that needle. The blood extended over the left cerebral cortical surface with thin subarachnoid hematoma on the parietal cortex, but did not extend on the right hemisphere and the basal cistern. The increase in ICP during production of SAH was minimal, mean value of 7.2 mmHg and ICP slowly returned to the basal level within 30 minutes. Rats were divided into 3 groups; rats 2 hours (SAH-2h, n = 7) and 48 hours (SAH-48h, n = 7) after production of SAH and rats 2hours after 0.04 ml saline injection for control (Control, n = 7). LCGU was studied according to the methods developed by Sokoloff.(ABSTRACT TRUNCATED AT 250 WORDS)