肿瘤血管源性脑水肿研究进展

临床上脑肿瘤周围水肿较为常见，过多的液体在脑肿瘤周围组织间隙积聚即细胞外液体最增多称为肿瘤源性脑水肿。其发生与肿瘤存存或生长有关，常沿脑白质内的神经纤维呈放射状（或指状）分布，通常被归类于血管源性脑水肿，并常致血脑屏障的异常，本文对脑瘤周罔水肿的发生机理、特点、影响州素及其治疗的研究进展作一综述。     

大剂量甲基泼尼松龙治疗急性重型外伤性脑水肿的初步报告

目的　探讨甲基泼尼松龙对急性外伤性脑水肿的治疗作用。方法　选择符合重型颅脑损伤 (GCS 3～ 8分 )病人 10 3例 ,给予大剂量甲基泼尼松龙冲击治疗 ,治疗前及治疗后 3、5、7天行头颅CT检查评价其对外伤性脑水肿的疗效 ,伤后 6个月以GOS评定临床效果。结果　甲基泼尼松龙治疗后 3、5、7天 ,Ⅲ度脑水肿的比率分别为 2 5 %、9 89%及 7 14 % ,较对照组明显降低 (P <0 0 5或P <0 0 1) ;伤后 7天 ,甲基泼尼松龙组和对照组脑水肿消退率分别为 6 1 17%和 47 6 2 % (P<0 0 1)。GOS评定恢复良好者达 71 84% ,死亡率为 18 45 % (P <0 0 5 )。结论　甲基泼泥松龙对急性外伤性脑水肿有显著治疗作用 ,可提高重型颅脑损伤的救治水平     

兔脑外伤后脑灌注压高低与脑水肿的实验研究

目的　了解不同灌注压对脑水肿的影响。方法　采用低温冷冻动物模型 ,将 30只动物随机分为三组 ,每组 10只 ,即高灌注压、适当的低灌注压、对照组。通过观察Evans蓝扩散距离、脑组织含水量的不同两项指标来观察脑水肿程度。结果　高灌注压组致伤灶Evans蓝扩散距离最大(1 85± 0 11cm) ,脑组织含水量也最高 (79 80 %± 0 71% ) ,适当低灌注压组上述两项指标最低 (1 71± 0 10cm ,76 99%± 0 6 2 % )对照组数值居中 (1 80± 0 12cm ,78 89%± 0 87% )。三者相互比较有显著性意义 (P<0 0 5 )。结论　灌注压越高越容易加重脑水肿。适当的灌注压降低 ,有助于改善脑水肿。     

Is Ca-activated potassium efflux involved in the formation of ischemic brain edema?

A possible role of Ca²⁺-activated potassium efflux in brain ischemia was studied using a rat focal cortical infarction model. Three days after ischemic insult, tissue contents of water, sodium, potassium and calcium ions were measured. Charybdotoxin, a specific inhibitor of Ca²⁺-activated potassium efflux, was found to reduce the formation of ischemic brain edema when a dosage of 0.15 mg/kg was given by i.v. 20–30 min prior to the onset of ischemic insult.     

脑挫裂伤患者脑脊液ApoE多态性与周围脑组织水肿的关系

目的探讨脑挫裂伤患者脑脊液载脂蛋白E基因(ApoE)多态性与周围脑组织水肿的关系。方法用聚合酶链反应-限制性片段多态性(PCR-RFLP)技术检测36例脑挫裂伤患者ApoE基因型频率,根据CT片计算脑水肿指数,统计学分析它们之间的关系。结果脑水肿指数与ApoE3呈负相关,而与ApoE4呈正相关,两者都具有统计学意义,脑挫裂伤患者脑脊液ApoE3和ApoE4与周围脑组织水肿具有相关性。结论脑挫裂伤患者脑脊液ApoE多态性可能是影响周围脑组织水肿的因素之一。     

大鼠液压脑损伤后皮层微血管改变与脑水肿的关系

目的探讨大鼠液压脑损伤后皮层微血管损伤情况及其与伤后脑水肿的关系。方法成年SD大鼠30只,随机分为正常组（n=6）、假手术组（n：6）、损伤组（n=18）,其中损伤组分为伤后6h、24h、72h三亚组,每亚组6只。利用液压冲击法建立大鼠颅脑损伤模型,显微镜下观察直接损伤侧和非直接损伤侧皮层微血管损伤隋况,CD34标记血管内皮细胞评价血管密度改变,干湿重法检测脑组织含水量的变化。结果大鼠皮层微血管损伤后6h可见血管支行迂曲、扩张、充血,伤后24h可见少量血栓形成,损伤后72h可见有较多血栓形成。损伤组CD34阳性细胞数明显低于假手术组和对照组（P〈0．05）,而脑组织含水量明显高于假手术组和对照组（P〈0．05）,而后两组无统计学差异（P〉O．05）。损伤组直接损伤侧皮层微血管损伤较非直接损伤组严重,而且伤后24h较伤后6、72h严重。结论颅脑损伤后脑微血管损伤为全脑性血管损伤,这可能是伤后脑水肿形成的机制之一。     

促红细胞生成素抑制大鼠创伤性脑水肿形成

目的探讨促红细胞生成素(erythropoietin,EPO)对大鼠创伤性脑水肿的影响及其的潜在分子机制。方法取SD大鼠90只,随机分为假手术组,创伤组和EPO组。创伤组:制作改进式Feeney's脑创伤模型;EPO组:伤后给大鼠腹腔注射重组人促红细胞生成素(5000 IU/kg)。伤后24 h,72 h和120 h,使用平衡木法评定各组大鼠行为学评分。伤后72 h时,检测各组大鼠脑含水量,脑组织胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)的磷酸化水平、水通道蛋白4(aquaporin 4,AQP4)mRNA和蛋白表达水平。结果在伤后各时间点,EPO组大鼠神经功能障碍的行为学评分也较创伤组有明显降低(均P<0.05)。伤后脑组织含水量由假手术组的78.76%±0.65%上升至创伤组的81.26%±0.40%(P<0.01),EPO组脑含水量则降低至79.71%±0.59%(与创伤组比较P<0.01)。与假手术组比较,创伤组ERK磷酸化的水平在伤后72 h明显上升(P<0.01),EPO组伤后ERK磷酸化水平则明显低于创伤组(0.369±0.046 vs.0.815±0.127,P<0.01);AQP4 mRNA和蛋白在伤后的表达水平均较假手术组明显增高(均P<0.01),EPO组AQP4 mRNA和蛋白的表达水平较创伤组均显著下降(均P<0.01)。结论EPO可抑制大鼠脑创伤后ERK信号通路的过度激活及下游AQP4的过表达,减轻大鼠的创伤性脑水肿。     

高压氧治疗外伤性顽固性脑水肿

目的探讨高压氧治疗外伤性顽固性脑水肿的疗效。方法将100例该病患者随机分成A、B两组。A组53例,在常规治疗情况下加用高压氧治疗(0.2MPa,吸纯氧40min×2次,其间吸空气10min)。B组47例,为常规治疗组,在使用甘露醇、速尿的基础上加用甘油及七叶皂苷等药物治疗。结果高压氧治疗外伤性顽固性脑水肿疗效明显优于常规药物治疗。结论对临床众多的外伤性顽固性脑水肿患者来说,高压氧治疗是目前疗效最好的方法。     

不同剂量甘露醇对大鼠缺血性脑水肿的治疗作用

为探讨甘露醇的治疗脑水肿的效果及最佳治疗方案，采用线栓法阻断大鼠大脑中动脉造成缺血性脑水肿，分别于缺血后１２ｈ，１６ｈ，２０ｈ，２４ｈ给予甘露醇一次，和于缺血后１２ｈ开始甘露醇，每隔２ｈ一次，用三次，五次和七次，甘露醇用量为０．５ｇ／Ｋｇ体重，对照组为缺血后１２ｈ，１６ｈ，２０ｈ，２４ｈ未用甘露醇。用脑组织含水量，病理变化及梗塞病灶面积三个指标来观察水肿的程度，结果：甘露醇对大鼠缺血性脑水肿的治疗     

Distribution of exudated FITC-dextrans in experimental vasogenic brain edema produced by a focal cryogenic injury

Summary Mice were subjected to cortical cryogenic brain injury, and FITC-dextrans (mol. wt. 20,000 or 150,000) were injected intravenously (i.v.). After a survival period of 4 h the distribution of the FITC-dextrans was determined by a histotechnical procedure described recently (Hultström et al. 1982a). This technique is based on freeze-drying and vapor fixation to immobilize the tracer and to provide tissue fixation.In and around the cryogenic injury both tracers leaked out of the cortical and the leptomeningeal vessels and spread into the brain parenchyma. They were seen as multiple, closely apposed droplets of fluorescent material best recognized by fluorescence microscopy under high magnification. The tracers were also taken up by neuronal perikarya and in glial cell nuclei of, presumably, astrocytic origin.Our study shows that the FITC-dextran technique can be used for experimental studies on the vasogenic form of brain edema. The patterns formed by the extravasated tracers have qualitative similarities to those produced by other more commonly used tracers, such as fluorochrome-labeled serum proteins and peroxidase.Supported by grants from the Swedish Medical Research Council, project no. 12X-03030, Trygg Hansa, Svenska läkarsällskapet, and Söderbergs stiftelser     

依达拉奉对颅脑损伤病人脑水肿及预后的影响

目的探讨依达拉奉对颅脑损伤病人脑水肿及预后的影响。方法采用随机双盲平行对照试验,98例急性颅脑损伤的病人随机分成治疗组50例和对照组48例,对照组按照急性脑损伤常规治疗,治疗组在常规治疗的基础上给予依达拉奉注射液30mg加入生理盐水注射液100ml中静滴,bid,共14d。2组在治疗后3、7、14、28d做头部CT检查,根据脑CT显示脑水肿最大层面的长×宽测算脑水肿面积表示脑水肿的程度,观察脑水肿的变化。于治疗前和治疗后28d分别进行格拉斯哥昏迷评分(GCS)。结果2组病人伤后脑水肿均逐渐加重而至第7d达高峰期,在第7d前2组脑水肿变化比较无统计学意义(P>0.05)。从第14～28d2组病人均明显减轻,但治疗组脑水肿减轻程度明显优于对照组(P<0.01);2组在第28dGCS评分均有提高,但治疗组GCS评分明显高于对照组(P<0.05)。依达拉奉治疗期间未发现明显不良反应。结论依达拉奉可以减轻颅脑损伤病人脑水肿,并能改善预后,无明显不良反应。     

Experimental brain tumors and edema in rats

Summary In this study an experimental intracerebral tumor has been investigated with special consideration of structures, which may be involved in edema production and/or resolution. For this purpose a cloned tumor cell line (RG1 2.2) has been injected stereotactically into the brain of BD-IX rats.The tumor has some characteristics in common with low differentiated oligodendroglioma in men. A honcycomb architecture may be seen in the center of the tumor. It is built up by rounded or elongated cells, which can be impregnated in parts. In the central area, cells exhibit a volominous digestive apparatus, composed of dictyosomes, vesicles, and some vacuoles with a membranaceous or homogeneous content. Tumor cells in the periphery show large processes and a small digestive apparatus. The sinusoidal tumor vessels are composed of an endothelium with many vesicles but no openings.     

一种新型血管源性脑水肿模型的建立

目的　建立简便易行、重复性好、无创伤、符合人类发病条件的ＶＢＥ 新模型。方法　Ｗｉｓｔａｒ鼠腹腔注射苯肾上腺素,测定微血管通透性,测量脑灰、白质水分含量,组织病理证实脑水肿。结果　血脑屏障通透性增高,脑水分增加（Ｐ＜ ０．０１）,灰质水分增加１１．６１％ ,白质水分增加１４．６４％ ,白质比灰质水分增加明显（Ｐ＜ ０．０５）。结论　注射苯肾上腺素制成ＶＢＥ动物模型,操作简便、无创伤、重复性好。     

Perivascular abnormalities in pediatric encephalopathy with fulminant brain edema

BackgroundAcute encephalopathy with acute brain swelling (ABS) is a recently proposed disease of unknown etiology, characterized by rapid progression to whole-brain swelling. To our knowledge, we reported the first case of a patient with acute encephalopathy with ABS wherein brain magnetic resonance imaging (MRI) abnormalities were noted prior to the diffuse brain swelling onset.Case presentationAn 11-year-old boy was admitted to our unit owing to prolonged disturbance of consciousness following febrile status epilepticus. At the initial visit, the vital signs were within the normal range, except for the body temperature and consciousness level (Glasgow Coma Scale 6; E1V1M4). The initial laboratory results showed elevated inflammatory marker levels and mild hyponatremia. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, whereas the myelin basic protein level was not elevated. Electroencephalography showed diffuse, high-amplitude slow waves.No abnormalities were detected on the initial brain computed tomography (CT) scan. However, at 11 h after the seizure onset, diffuse hyperintense lesions were observed throughout the cerebrum on T2-weighted brain MRI. The patient was diagnosed with acute encephalopathy and received methylprednisolone-pulse therapy (1 g) with high-dose gamma globulin (1 g/kg) administration. At 14 h after the seizure onset, the patient was declared brain-dead; the brain CT findings revealed whole-brain swelling and herniation.ConclusionOur findings were suggestive of a perivascular pathophysiology and may be used for subtyping acute encephalopathy. In cases where such findings are observed, subsequent development of severe diffuse brain swelling should be considered.     

Aquaporin-4 and ischemic brain edema

OBJECTIVE： To investigate the relationship of aquaporin 4 （AQP4） and brain edema. DATA SOURCES： Using the terms of ＂aquaporin-4, brain edema＂, we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages. Meanwhile, we also searched China National Knowledge Infrastructure （CNKI） for related studies. STUDY SELECTION： The collected data were selected firstly. Studies on AQP4 and brain edema were chosen and their full-texts were searched for, and those with repetitive or review studies were excluded. DATA EXTRACTION： Totally 146 related studies were collected, 42 of them were involved and the other 104 studies were used for reading reference data. DATA SYNTHESIS： AQP4 is a selective water permeable integral membrane protein. It is mainly expressed in astrocytes and ependymocyte, and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels. Phosphorylation is involved in the regulation of AQP4. AQP4 participates in the formation of brain edema caused by various factors. Studies on the structure and pathological changes of AQP4 are still in the initial stage, and the role and mechanism of AQP4 in the formation of brain edema is very unclear. CONCLUSION： AQP4 plays a critical regulating role in the formation of ischemic brain edema, but whether it is regulated by drugs lacks reliable evidence.     

大鼠气体冲击致脑损伤后脑水肿的变化

目的 探讨颅脑创伤后脑水肿的变化,并寻找在体研究脑水肿的方法。方法 气体冲击致大鼠中度颅脑创伤后,以干湿重法和多频率阻抗法监测伤后脑水肿的变化。结果 伤后3小时,伤区脑组织巳明显水肿,伤后24-72小时,伤区脑水肿达高峰,伤后7天基本恢复。多频率阻抗测试表明,伤后早期细胞外液电阻（Re）及其与细胞内液电阻（Ri）的比Re/Ri明显下降,提示发生了细胞外水肿;伤后6小时后Ri明显下降,Re/Ri明显增加,提示细胞内水肿的发生。结论 颅脑创伤后早期发生血管源性水肿,而随之发生细胞毒性水肿,两种水肿的发展使脑水肿于伤后24-72小时达高峰。多频率阻抗测试可在体监测脑水肿的变化。     

胰蛋白酶抑制剂对实验性缺血性脑水肿的作用

目的观察各种胰蛋白酶抑制剂对大鼠缺血性脑水肿的作用。方法大鼠脑缺血模型采用线栓法，脑含水量测定采用称重法，常规病理学检查。结果５５ｍｇ／ｋｇ和１６５ｍｇ／ｋｇ胰蛋白酶抑制剂（ＳＢＴＩ）对ＬＭＣＡＯ３ｈ大鼠脑含水量无显著影响（Ｐ均＞０．０５）；６６０００ＫＩＵ／ｋｇ特血乐、５００００Ｕ／ｋｇ尿胰蛋白酶抑制剂（ＵＴＩ）可显著降低脑水肿大鼠脑含水量（Ｐ均＜０．０５），并可减轻缺血区神经元变性及间质水肿程度。结论６６０００ＫＩＵ／ｋｇ特血乐、５００００Ｕ／ｋｇＵＴＩ具有减轻实验性缺血性脑水肿的作用。