急性重型颅脑外伤患者血管内皮生长因子的表达及意义

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)在重型急性颅脑外部损伤患者血清中的表达水平及临床价值。方法取重型急性颅脑外部损伤患者80例为研究对象,设为观察组,取同期健康体检者40例为参照组,通过酶联免疫吸附法(ELISA)对2组受试者血清中VEGF的表达水平进行检测。结果伤后第1、3、7及14天,观察组血清中VEGF表达水平明显高于参照组,差异有统计学意义(P<0.05);观察组患者预后与血清VEGF表达水平呈正相关,且血清VEGF早期表达越高,患者预后越好。结论在重度急性颅脑损伤早期,患者血清VEGF表达水平表现为动态性升高,因而可视为该类患者预后判断的一项有效指标。     

血管内皮生长因子与人脑动静脉畸形的关系

目的　探讨血管内皮生长子因子与脑动静脉畸形的关系。方法　 14例AVMs行显微外科手术切除AVMs和AVMs周围脑组织、8例正常脑血管标本及周围脑组织 ,分别提取总RNA和 4 %PFA PBS固定石蜡包埋、原位杂交、RNA狭逢斑点杂交和免疫组化检测VEGF在脑AVMs中的改变。结果　VEGFmRNA弥散分布于血管的各层组织和AVMs周围脑组织中 ,与正常组织比 ,AVMs、AVMs周围脑组织VEGFmRNA表达增高 ;VEGF蛋白主要位于畸形血管的的血管内膜层 (内皮细胞 )。结论　VEGF可能参与脑AVMs的发生发展。     

缺氧诱导人脑动静脉畸形血管内皮细胞生长因子表达

目的 探讨缺氧条件下体外培养的人脑动静脉畸形（cAVM）血管内皮细胞中血管内皮细胞生长因子（VEGF）基因表达与细胞超微结构变化。方法 采用组织块贴壁法对cAVM血管内皮细胞进行培养和形态学观察。采用免疫组化方法检测细胞中第八因子相关抗原（FⅧ-RA）的表达，采用RT-PCR技术观察静态和缺氧状态下2h、4h、8h血管内皮细胞VEGF mRNA表达。采用酶联免疫吸附实验（ELISA）检测每组细胞上清液中VEGF蛋白含量；在透射电镜下观察细胞超微结构的变化。结果 体外培养的活细胞具有单层“卵石样”排列的典型特征．95％以上的细胞FⅧ-RA染色阳性。血管内皮细胞vEGF蛋白和mRNA表达在缺氧2h开始升高（P〈0．05），并持续至缺氧8h（P〈0．01）：细胞线粒体丰富。核糖体及粗面内质网逐渐增多。结论 缺氧可能在基因转录水平诱导VEGF表达，后者通过自分泌途径刺激cAVM血管内皮细胞增殖。     

中枢神经系统血管畸形性疾病中VEGF的表达

有关血管内皮细胞生长因子 (VEGF)在实体肿瘤生长过程中的作用已有大量研究 ,但有关VEGF在中枢神经系统血管畸形性疾病中的表达的研究却很少 ,且开展得较晚。David和William等人发现血管畸形性疾病的病人的血管内皮细胞 ,内皮下层和血管周边组织VEGF表达增强。其机理可能与脑组织缺氧 ,以及静脉壁 ,静脉窦壁承受较大的撕脱压力或者血管破裂而激发VEGF表达上调有关。     

高压氧对大鼠脊髓损伤后血管内皮生长因子表达的影响

目的通过观察高压氧对成年大鼠脊髓损伤后不同时期血管内皮生长因子（VEGF）表达变化的影响,探讨高压氧对脊髓损伤的治疗作用机制。方法雌性SD大鼠55只,体质量250-300g。随机分为脊髓损伤组（对照组）、脊髓损伤＋高压氧治疗组各25只（n=5）,假手术组5只。采用改良A llen＇s法制作T8脊髓打击伤动物模型,各组分别于伤后1 d、1 w、2 w、4 w和8 w进行行为学观察,运动功能评分方法（BBB）评分后损伤部位取材,免疫组化染色及图像分析检测组织中VEGF的表达。结果假手术组的评分21分,治疗组和对照组与假手术组比较在各时间点评分明显降低,治疗组在各时间段BBB评分明显高于对照组（P〈0.05）。假手术组显示除脊髓中央管周围可见到极少量VEGF表达外,其它部位几乎不表达;对照组脊髓损伤1 d VEGF在大鼠脊髓损伤区及损伤周边区高表达,主要出现在软脊膜和脊髓灰、白质血管壁上的血管内皮细胞胞浆内,脊髓灰、白质内的神经胶质细胞和巨噬细胞胞浆内也出现表达,一般脊髓白质中更为多见,1 w后下调,而治疗组1 d至2 wVEGF的表达较对照组明显增加,差异有显著性（P〈0.05）,4 w、8 w时各组比较无统计学差异。结论急性脊髓损伤可上调VEGF在脊髓血管内皮细胞、胶质细胞和巨噬细胞内的表达,高压氧可能通过促进VEGF表达,促进血管内皮细胞生长从而对脊髓损伤起到治疗作用。     

垂体瘤血管内皮生长因子表达及其意义

目的：探讨血管内皮生长因子在垂体瘤中的表达及其意义。方法：应用免疫组化法对20例复发、26例未复发的人脑垂体瘤中血管内皮生长因子表达进行检测。结果：复发组垂体瘤中血管内皮生长因子表达较未复发组明显增高,两组有显著性差异（P＜0．01）。结论：血管内皮生长因子在垂体瘤血管形成中起重要作用,可能与垂体瘤的发展与复发有关。     

垂体瘤血管内皮生长因子表达及其意义

目的 :探讨血管内皮生长因子在垂体瘤中的表达及其意义。方法 :应用免疫组化法对 2 0例复发、2 6例未复发的人脑垂体瘤中血管内皮生长因子表达进行检测。结果 :复发组垂体瘤中血管内皮生长因子表达较未复发组明显增高 ,两组有显著性差异 (P <0 0 1)。结论 :血管内皮生长因子在垂体瘤血管形成中起重要作用 ,可能与垂体瘤的发展与复发有关     

急性脑梗死患者血清血管内皮生长因子的测定

目的　探讨急性脑梗死与血管内皮生长因子 (VEGF)的关系。方法　对 3 0例急性脑梗死患者和 40例健康人血清血管内皮生长因子含量进行测定。患者采血时间为病后第 2天或第 3、4天 ,取均数与对照组比较。结果　 3 0例急性脑梗死患者血清 VEGF含量为 (2 95 .0 4± 3 5 .73 ) pg/ ml,对照组为 (13 7.71± 11.5 3 ) pg/ m l,两组比较差异显著。结论　急性脑梗死患者血清 VEGF升高 ,提示 VEGF是脑梗死急性期的自我保护机制之一。     

内皮抑素和血管内皮生长因子在脑胶质瘤中的表达及意义

目的探讨内皮抑素(ES)和血管内皮生长因子(VEGF)在人脑胶质瘤中的表达和意义。方法采用免疫组织化学方法,对45例脑胶质瘤和5例正常脑组织标本中ES和VEGF的表达进行测定。结果Ⅲ-Ⅳ级胶质瘤中ES和VEGF表达水平明显高于Ⅰ-Ⅱ级胶质瘤和正常脑组织,差异有显著性意义(P<0.01);Ⅰ-Ⅱ级胶质瘤中VEGF表达水平显著高于正常脑组织(P<0.05);胶质瘤中ES与VEGF的比值和胶质瘤的分级呈负相关。结论ES和VEGF的协同作用可能在人脑胶质瘤细胞侵袭性生长及恶性发展中起重要作用,且有可能与胶质瘤的恶性程度及预后有关。     

脑干血管畸形的显微手术治疗(附19例报告)

目的 探讨脑干血管畸形的显微外科手术治疗方法和预后.方法 显微手术切除脑干血管畸形19例.6例经枕下正中第四脑室底入路切除;9例经枕下乙状窦后入路切除;3例经小脑延髓裂入路切除;1例经枕下正中入路上抬蚓垂后切除.结果 19例病灶均镜下全切,其中海绵状血管瘤15例,动静脉畸形4例.13例症状改善,5例出现并发症,1例因下呼吸道感染死亡.随访中GOS 5分15例,GOS 4分2例,GOS 3分1例.MRI复查无病灶残留.结论 在恰当选择手术适应证、手术时机和手术入路的基础上,运用娴熟的显微外科技术,脑干血管畸形的手术治疗结果是令人满意的.

Abstract：

Objective To investigate the microsurgical treatment of brainstem vascular malformation and evaluate the surgical outcome. Method Brain stem vascular malformations in 19 cases were resected by microsurgical techniques. Six cases of cavernous malformations ( CM ) in the dorsal of pons and medulla underwent operations via through the base of the forth ventrical approach. Another nine cases of CM in lateral and ventral lateral pons were treated via suboccipito - retrosigmoid approach. Three cases of arteriovenous malformation(AVM) in cerebellomedullary fissure were treated via telovelar approach. One case of AVM in the dosal medulla were resected via transvermian approach. Results All the lesions were totally resected. Pathologic diagnosis were CM( 15 cases) and AVM(4 cases). The diameter of all the CM were less than 1 centimeter. One AVM was 1.5 centimeter in diameter, the other two lesions was 2. 0 centimeter, the last one was 2. 5 centimeter. The functional disorders were improved after operation in 13 cases. Complications appeared in five patients, which improved between one week and three months. One patient died of sever pneumonia. During two months to six years after operation, the brainstem vascular malformation didn't recrudesce and re - bleed. No one patient appeared new syndromes. Conclusions The microsurgical management of brainstem vascular malformation can effectively prevent re - bleeding. Selecting different surgical approach basing on the locations can reduce the neurofunction damage. In order to accelerate the recovery of damaged brainstem, early surgery should be choosen for the patients with surgical indications. Basing on the correct choice of surgical indications, using the extensive knowledge of microanatomy,new concept of minimal invasive surgery and skillful microsurgical techniques, the surgical results of brainstem vascular malformation are satisfactory.     

Spinal vascular malformations in non-perimesencephalic subarachnoid hemorrhage

Objective   In patients with non-traumatic subarachnoid hemorrhage (SAH) and no evidence for a cerebral aneurysm on angiography, a frequent cause of the hemorrhage is perimesencephalic hemorrhage or other cerebral vascular pathology. In some patients no cause is found. The exact incidence of a spinal vascular malformation (SVM) as the origin for the SAH is not known. We assessed the occurrence of SVM in angiogram-negative, non-perimesencephalic subarachnoid hemorrhage (NPSAH). Methods   47 patients (from a consecutive cohort of 632) were identified with an angiogramnegative, non-perimesencephalic subarachnoid hemorrhage and 42 of these were analyzed by performing MR-imaging of the complete spinal neuraxis with additional spinal angiography on indication. Results   In four patients a spinal vascular malformation was identified as the cause of the SAH, indicating an incidence of 9 % of SVM in NPSAH, and an incidence of 1 % of SVM in all patients with SAH. Interpretation   Systematic analysis of angiogram-negative, non-perimesencephalic subarachnoid hemorrhage by MR imaging of the complete spinal neuraxis yields a higher incidence of SVM than previously documented. We recommend MR imaging of the complete spinal neuraxis in patients with a non-perimesencephalic subarachnoid hemorrhage in whom no cause for the hemorrhage has been found.     

脑动静脉畸形破裂出血病人中Ang1、Ang2、VEGF、LP的表达和意义

目的研究血管生成素1(angiopoietin 1,Ang1)、血管生成素2(angiopoietin 2,Ang2)、血管内皮生长因子(vascular-endothelial growth factor,VEGF)及瘦素(leptin,LP)在脑动静脉畸形(AVM)破裂出血病人中的表达和意义。方法收集手术切除的AVM标本28例,将14例有近期破裂出血史的病人作为AVM出血组,14例无明显破裂出血史的病人作为AVM未出血组,采用免疫组织化学法检测2组标本Ang1、Ang2、VEGF及LP的表达,并进行统计分析。结果免疫组织化学法显示:Ang1、Ang2、VEGF及LP在2组血管内皮细胞中均有阳性表达;与AVM未出血组比较,AVM出血组的血管内皮细胞中Ang2、VEGF、LP表达显著增强(均P<0.01),而Ang1的表达较弱(P>0.05)。结论 Angl、Ang2、VEGF及LP在AVM的畸形血管中存在特异性表达,尤其是Ang2、VEGF及LP可能与AVM的进展及破裂出血有密切关系。     

小脑血管畸形显微手术治疗的临床分析

目的探讨小脑血管畸形的临床特点及手术治疗方法与疗效。方法回顾性分析72例小脑血管畸形病人的临床资料．采用乙状窦后入路或枕下后正中入路进行手术。结果72例病人均手术全切病灶。术后病理结果：动静脉畸形（AVM）67例,海绵状血管瘤（CM）3例,静脉畸形（VM）2例。术后GOS评分：5分64例,4分4例,3分1例,2分1例,1分2例。随访4个月～13年,恢复良好64例,轻残4例,重残1例,植物生存状态1例,死亡2例。无复发病例。术前GCS评分≥8分的AVM病人,其术后GOS评分较GCS评分〈8分者高（P〈0．05）。结论小脑血管畸形应尽早行手术切除治疗,术中采用合适的手术入路、适当的手术技巧,可取得良好的手术效果。AVM病人术前GCS评分≥8分的病人恢复好,〈8分病人恢复较差。     

Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas

C. Christov, H. Adle-Biassette, C. Le Guerinel, S. Natchev and R. K. Gherardi (1998) Neuropathology and Applied Neurobiology 24, 29–35 Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas Vascular endothelial growth factor (VEGF) appears to be implicated in tumour angiogenesis. In the present study immunohistochemical expression of VEGF was evaluated in 34 oligodendrogliomas (13 grade II, 21 grade III [WHO]). VEGF immunoreactivity was found in 31 of 34 cases. Expression of VEGF was observed in endothelial cells and some vascular smooth muscle cells, but not in neoplastic oligodendrocytes. Vessel counts, percentages of VEGF-positive vessels and vessels with vascular endothelial proliferation were assessed. The degree of VEGF labelling and vascular-endothelial proliferation in each vessel were evaluated using a 3 degree intensity score. Expression of VEGF was higher in grade III than in grade II oligodendrogliomas as assessed by percentage of VEGF positive vessels (55.8 ± 29.2% vs 17.0 ± 19.0% [P < 0.001]) and by VEGF immunostaining intensity (1.90 ± 0.60 vs 0.90 ± 0.40 [P < 0.001]). VEGF expression did not correlate with vessel density. Intensity of VEGF expression correlated positively with that of vascular-endothelial proliferation in grade III tumours (r=+0.47 [P < 0.05]). The percentage of VEGF positive vessels showed some degree of positive correlation with the percentage of vessels showing vascular-endothelial proliferation (r=+408 [P < 0.10]). Within individual grade III tumours 67.5 ± 29.6% of all vessels with vascular-endothelial proliferation were VEGF-positive and 31.0 ± 20.5% of all VEGF-positive vessels showed no evidence of vascular-endothelial proliferation. We conclude that (i) expression of VEGF is observed in the vasculature of oligodendrogliomas; (ii) marked expression of VEGF is observed in grade III oligodendrogliomas; (iii) VEGF may be one of the interrelated causative stimuli acting in concert to induce vascular-endothelial proliferation.     

MVD、VEGF及Ki-67在颅咽管瘤中的表达与意义

目的探讨颅咽管瘤中MVD、VEGF及Ki-67表达与意义。方法根据病理亚型、形态学特征及复发情况,将47例颅咽管瘤按不同分类方法分为成釉质细胞型30例,鳞状乳头型17例;原发31例,复发16例;实性为主肿瘤10例,囊性为主肿瘤37例。SP法检测肿瘤标本MVD、VEGF及Ki-67表达,统计分析不同分类的组间表达差异。结果鳞状乳头型肿瘤MVD、VEGF的表达明显高于成釉质细胞型(均P0.001),而Ki-67在两种病理亚型之间无显著差异(P0.05);囊性为主的肿瘤中VEGF表达明显高于实性为主的肿瘤(P=0.018),而MVD、Ki-67在两种形态学分组之间无显著差异(均P0.05);原、复发组间MVD、VEGF及Ki-67均无显著差异(均P0.05)。在本组颅咽管瘤中,MVD与VEGF显著相关(P=0.014),两者均与Ki-67无显著相关(均P0.05)。结论 MVD、VEGF的测定可为颅咽管瘤的血管发生提供依据,VEGF的表达与肿瘤囊性结构形成密切相关,单独检测MVD、VEGF和Ki-67其中一项指标不能预测颅咽管瘤复发。     

体外培养人脑动静脉畸形血管内皮细胞中VEGF表达增加

目的探讨体外培养的人脑动静脉畸形血管内皮细胞和正常脑血管内皮细胞中血管内皮细胞生长因子(VEGF)表达水平的差异。方法采用组织块贴壁法对人脑动静脉畸形血管内皮细胞进行培养和形态学观察;免疫组化检测CD31和vWF抗原验证内皮细胞;采用RT-PCR和Western blot技术检测脑动静脉畸形血管内皮细胞VEGF mRNA和蛋白表达,并与和正常脑血管内皮细胞进行比较。结果体外培养的内皮细胞CD31和vWF染色阳性率达95%以上。人脑动静脉畸形血管内皮细胞中VEGF mRNA和蛋白表达均显著升高(P0.05)。结论体外培养的人脑动静脉畸形内皮细胞中VEGF的高表达,提示血管生成在脑动静脉畸形的发病机制中起重要作用。     

Neuronotrophic activities in cerebrospinal fluid of head trauma patients

Neuronotrophic factors (NTFs) are agents required for neurons to survive in tissue culture. In this study, we investigated the presence of NTFs in cerebrospinal fluid (CSF) of patients with central nervous system (CNS) injury. Cerebrospinal fluid was collected from 15 patients with acute CNS lesions in whom ventricular catheters had been placed to monitor and to facilitate the control of intracranial pressure. Neuronotrophic activity within the CSF was assayed using cultures of neurons derived from fetal rat hippocampus and embryonic chick cerebral cortex. Cerebrospinal fluid from all 15 patients contained NTFs which supported the survival of rat hippocampal neurons. Survival of chick cortex neurons was supported by eight of nine CSF samples. In the 11 patients from whom consecutive CSF samples were available, NTF activity assayed in rat hippocampal cultures tended to decrease during the first several days after CNS injury. In CSF collected from three patients by lumbar puncture for diagnosis of "nontraumatic" conditions, no NTFs were detectable. NTFs supporting hippocampal neurons were also detected in extracts of blood clot obtained from normal volunteers. Neuronotrophic activity in the CSF was heat sensitive, nondialyzable, and macromolecular, suggesting its association with a protein(s). These observations suggested that (i) NTFs are detectable in human CSF after CNS injury, (ii) NTFs appear in response to the injury itself, and (iii) at least some human NTFs can support the survival in culture of nonhuman CNS neurons.     

Hydroxysafflor yellow A improves learning and memory in a rat model of vascular dementia by increasing VEGF and NR1 in the hippocampus

Hydroxysafflor yellow A (HSYA) has angiogenesisregulating and neuro-protective effects, but its effects on vascular dementia (VaD) are unknown. In this study, 30 adult Sprague-Dawley rats were randomly allocated to five groups: normal, sham-operation, VaD alone (bilateral carotid artery occlusion), VaD plus saline (control), and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation (LTP) method. Vascular endothelial growth factor (VEGF) and N-methyl-Daspartic acid receptor 1 (NR1) expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze (P < 0.05), and the LTP at CA3-CA1 synapses in the hippocampus was enhanced (P < 0.05). Western blot in the late-phase VaD group showed slight up-regulation of VEGF and downregulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NR1. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.