高温对重型颅脑损伤后乳酸、Na^＋－K^＋－ATP酶和脑水肿的影响

目的探讨大鼠重型颅脑损伤后高温对伤灶区脑组织乳酸、Na^＋－K^＋－ATP酶和脑水肿的影响。方法90只SD大鼠随机分为假手术组、颅脑损伤组、伤后高温组，每组又按处死时间点（伤后4h、1d、3d、5d和7d）分为五个亚组，每亚组6只。取伤灶区脑组织测含水量、乳酸含量和Na^＋－K^＋－ATP酶活性并行电镜检查。结果高温组脑组织含水量和乳酸含量在伤后各时间点均显著高于颅脑损伤组和假手术组（P〈0.05），而Na^＋－K^＋－ATP酶含量显著低于颅脑损伤组和假手术组（P〈0.05），电镜检查发现高温组神经细胞肿胀、血脑屏障破坏程度较颅脑损伤组明显加重。结论颅脑损伤后高温增加脑组织乳酸生成，同时Na^＋－K^＋－ATP酶活性下降，脑水肿加重，故在颅脑损伤后应保持体温在正常范围内，避免体温升高。     

乌司他丁对创伤性脑水肿合并海水淹溺性肺水肿大鼠的治疗作用

目的 探讨乌司他丁对创伤性脑水肿(TBE)合并海水淹溺性肺水肿(PE-SWD)大鼠的治疗作用. 方法 32只SD大鼠按照随机数字表法分为对照组(8只)和治疗组(24只).脑侧方液压打击伤+气管内灌注海水建立大鼠TBE合并PE-SWD动物模型.伤后治疗组腹腔注射不同剂量(2500、50 000、100 000 U/kg)乌司他丁溶液1 mL,对照组腹腔注射1 mL生理盐水,伤后24 h观察脑、肺组织含水量变化,血清、脑组织、肺组织白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量的变化以及脑、肺组织病理学变化. 结果 乌司他丁治疗后.TBE合并PE-SWD大鼠脑、肺组织含水量及血清、脑组织、肺组织IL-1β和TNF-α含量均明显降低,差异有统计学意义(P<0.05);脑、肺组织病理学改变有明显减轻. 结论 乌司他丁可以减轻TBE及PE-SWD.其机制与抗炎作用有关.     

大鼠重型颅脑损伤急性期水通道蛋白4的表达

目的探讨水通道蛋白（AQP4）在大鼠重型脑外伤急性期的表达变化及其与脑水肿间的关系。方法49只成年雄性SD大鼠,随机分为对照组及实验组（伤后4h、8h、12h、24h、5d共5组）。制作重度冲击加速性损伤模型,分别于伤后4h、8h、12h、24h、72h、5d采用干湿比重法测脑组织含水量,原子吸收分光光度法测定Na^＋、K^＋含量,Evans Blue（EB）测定法观察大鼠血-脑屏障（BBB）通透性变化,半定量逆转录聚合酶链反应（RT-PCR）检测脑组织AQP4 mRNA表达及其变化。结果脑组织AQP4 mRNA在伤后4h开始表达上调,8h、12h依次增高,24h达到峰值（P〈0.05）,3d时仍维持较高水平,伤后5d有所降低。脑含水量、Na^＋含量的变化与AQP4 mRNA表达变化一致。经相关性分析,AQP4 mRNA的表达与脑含水量及脑EB含量均呈正相关（P〈0.05）。结论重型脑损伤急性期,AQP4 mRNA表达的变化与颅脑损伤后BBB的破坏及脑水肿的形成和发展密切相关。AQP4可能参与重型脑损伤后脑水肿的形成并起重要作用。     

促红细胞生成素对颅脑创伤休克大鼠的保护作用

目的 探讨重组人促红细胞生成素r-HuEPO)对大鼠伴有休克的颅脑创伤的保护作用.方法 114只Wistac大鼠随机分为假手术组n=6)、单纯脑创伤组n=36)、合并休克的脑创伤组n=36)及r-HuEPO治疗组n=36).采用自由落体法建立大鼠颅脑创伤模型,股动脉放血造成休克模型.分别于伤后不同时间点,应用Epics XL流式细胞仪检测颅脑创伤后神经细胞凋亡情况,利用Castrase-3分光光度法检测试剂盒测定Caspase-3活性变化,并用干湿重法测定脑组织含水量.结果 单纯脑创伤组及合并休克的脑创伤组细胞凋亡率、Caspase-3活性及脑组织含水量均较假手术组明显升高P<0.05).与模型组相比,r-HuEPO治疗组Caspase-3活性及细胞凋亡率显著降低P<0.05),脑水肿虽有好转,但无统计学意义P>0.05).结论 r-HuEPO可通过降低Caspase-3的活性,减少细胞凋亡,起到脑保护作用.     

N-乙酰半胱氨酸对大鼠颅脑损伤后炎性因子表达的影响

目的探讨N-乙酰半胱氨酸（NAC）对大鼠颅脑损伤后促炎症细胞因子白细胞介素-6（IL-6）和抗炎症细胞因子白细胞介素-10（IL-10）的表达水平的影响及其脑保护作用。方法采用Feeney法制作颅脑损伤模型,将75只雄性Wistar大鼠随机分为假手术组、颅脑创伤组及NAC干预组。酶联免疫吸附测定（ELISA）分析假手术组、NAC干预组及颅脑创伤组IL-6和IL-10血清表达水平的变化,并用干湿重法测定脑组织含水量。结果颅脑创伤组IL-6表达时相为高峰期时IL-10表达水平也较高,二者存在正相关关系;而NAC干预组IL-6表达水平较颅脑创伤组自3h后相应时间点明显降低（P〈0.01）,IL-10在3h后相应时间点明显升高（P〈0.01）;NAC干预组伤侧脑组织含水量在3d和5d时较假手术组相应时间点脑组织含水量下降,且具有统计学意义（P〈0.05）,余时间点伤侧脑组织含水量虽有下降但无统计学意义（P〉0.05）。结论NAC可能通过抑制颅脑损伤后促炎因子的过度表达,同时可提高抗炎因子的表达水平,从而减轻脑创伤后过度炎性反应,减轻脑水肿,发挥其脑保护作用。     

磁共振成像评估丁苯酞软胶囊对创伤性脑水肿大鼠的治疗作用

目的运用磁共振成像探索大鼠创伤性脑水肿的演变规律及丁苯酞软胶囊对其的治疗作用。方法 SD雄性大鼠175只。随机分为非干预组、干预组和正常对照组。采用Marmarou法制作创伤性脑水肿大鼠模型,造模成功后分别于6 h、12 h、1 d、3 d、7 d行磁共振成像扫描、HE染色、脑组织含水量测定、伊文思蓝渗出量测定。结果磁共振成像、HE染色、和脑组织含水量测定结果提示与对照组相比,非干预组和干预组脑组织可见明显脑水肿,其中以损伤后24 h最明显,3 d后开始减轻。干预组较非干预组脑水肿程度明显减轻。伊文思蓝渗出检测提示,创伤性脑损伤后伊文思蓝渗出量增多,其中以6 h渗出量最多。非干预组较干预组渗出明显。结论创伤性脑损伤后,继发血管源性脑水肿和细胞毒性脑水肿,其中以1 d时脑水肿最明显,丁苯酞软胶囊能明显减轻脑损伤后脑水肿的形成。     

高温对重型颅脑损伤后乳酸、Na+-K+-ATP酶和脑水肿的影响

目的 探讨大鼠重型颅脑损伤后高温对伤灶区脑组织乳酸、Na+-K+-ATP酶和脑水肿的影响.方法 90只SD大鼠随机分为假手术组、颅脑损伤组、伤后高温组,每组又按处死时间点(伤后4 h、1 d、3 d、5 d和7 d)分为五个亚组,每亚组6只.取伤灶区脑组织测含水量、乳酸含量和Na+-K+-ATP酶活性并行电镜检查.结果 高温组脑组织含水量和乳酸含量在伤后各时间点均显著高于颅脑损伤组和假手术组(P＜0.05),而Na+-K+-ATP酶含量显著低于颅脑损伤组和假手术组(P＜0.05),电镜检查发现高温组神经细胞肿胀、血脑屏障破坏程度较颅脑损伤组明显加重.结论 颅脑损伤后高温增加脑组织乳酸生成,同时Na+-K+-ATP酶活性下降,脑水肿加重,故在颅脑损伤后应保持体温在正常范围内,避免体温升高.     

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。     

雪莲黄酮对大鼠创伤性脑水肿的治疗作用及其机制的初步研究

目的研究雪莲黄酮对大鼠创伤性脑水肿的治疗作用及其机制。方法采用液压冲击法制作大鼠脑创伤模型,用雪莲黄酮注射液进行治疗。治疗后不同时间取伤灶及其周围脑组织进行含水量和与脂质过氧化有关的一些指标进行检测。结果脑创伤后6h、24h及3d伤灶及其周围脑组织中含水量及丙二醛含量明显增加(P<0.01),而超氧化物岐化酶含量明显减少(P<0.01),但雪莲黄酮能逆转上述变化。结论雪莲黄酮对大鼠创伤性脑水肿有一定的治疗作用,作用机制可能与其抗脂质过氧化作用有关。     

血管内皮细胞生长因子的表达对创伤后脑组织含水量的影响

目的探讨颅脑创伤后挫裂伤脑组织中血管内皮细胞生长因子（vascularendothelialgrowth{actor,VEGF）的表达与颅脑创伤后继发脑水肿的关系。方法选用成年、健康、雄性Wiste大鼠60只,随机分为实验组和对照组。前者按损伤后不同时间点分为3h、72h、7d组,每组15只大鼠。我们采用Marmarou自由落体撞击法建立局灶性脑挫裂伤动物模型,实验组大鼠损伤后按预定的时间点断头处死,开颅切除损伤及邻近损伤区标本,而对照组则不致伤,监测内容同损伤组。采用免疫组化技术（SP法）及显微镜观察阳性细胞数,检测创伤后不同时间点脑损伤组织中VEGF表达情况。采集的标本采用干湿重法测定损伤脑组织的含水量。结果正常脑组织未检测到VEGF蛋白表达;脑创伤后3h脑组织中VEGF表达明显增加,72h达到高峰,7d后表达减少,与相同时间点脑组织含水量呈正相关。结论VEGF可能在颅脑创伤后继发脑水肿发生、发展中起重要作用。     

Experimental peritumorous edema

Summary In 23 cats, vasogenic brain edema was produced by stereotaxic xenotransplantation of the glial cell clone RG 2 into the internal capsula of the brain. The resulting tumor grew to a diameter of 0.5–1 cm within 2–3 weeks; thereafter it was either rejected, or the animal died. One to 4 weeks after the implantation, the EEG, intracranial pressure, and blood flow were recorded using labelled microspheres. The permeability of the blood-brain barrier was tested with Evans blue, and the animal was subsequently killed by air embolism. Tissue samples were taken from peritumorous and contralateral white and grey matter, and assessed for water and electrolyte content, and blood flow. Adjacent sections were fixed in formalin and investigated for permeability disturbances of the blood-brain barrier, and for the spread of peritumorous edema by tracing intracerebral serum albumins with a specific immunofluorescent technique. Permeability disturbances of the blood-brain barrier were restricted to the tumor, but there was, after 2 weeks, massive leakage of serum albumins into the surrounding white matter. Water content in the peritumorous white matter increased from 69.1±0.9 to more than 80%, reaching a maximum after 2–3 weeks. Sodium content rose from 163 to 390 meq/kg d.w., whereas potassium remained almost constant. Blood flow in the edematous white matter was markedly reduced from 32.2±5.6 to 16.5±1.4 ml/100 g/min after 4 weeks. The decrease was due to the expansion of tissue volume and not to an increase in vascular resistance. Fourier transform of the EEG revealed a significant slowing of the mean frequency on the affected side in 6 out of 13 animals. There was no consistent correlation with either the duration of survival, the water content, electrolyte shifts, blood flow or intracranial pressure. EEG changes, in consequence, seem to result from direct influence of the tumor on brain parenchyma, rather than from peritumorus edema or intracranial hypertension.Supported by the Deutsche Forschungsgemeinschaft     

Pathophysiological aspects of brain edema

Summary Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In theischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthday     

水孔蛋白-1,4与脑水肿

肿瘤、外伤、缺血性卒中等中枢神经系统疾病均伴有脑水肿的发生，主要分为血管源性和细胞毒性脑水肿，大多数病理过程中两类脑水肿同时存在。但目前尚缺乏普遍有效、副作用少的治疗脑水肿药物。例如甘露醇通过渗透性脱水降低脑组织含水量，但对血脑屏障破坏的病灶，甘露醇进入病灶区脑组织，反而可能加重脑水肿：例如激素对肿瘤周围脑水肿有肯定的控制作用，但对外伤性脑水肿无肯定疗效。水孔蛋白faquaporin，AQP）的发现为研究脑水肿的发生机制和治疗指明了方向。     

Differentiation of pure vasogenic edema and tumor-infiltrated edema in patients with peritumoral edema by analyzing the relationship of axial and radial diffusivities on 3.0T MRI

Object

The purpose of this study was to analyze the relationship of axial diffusivity (AD) and radial diffusivity (RD) in peritumoral edema of high grade glioma, metastasis, and meningioma, and to differentiate tumor-infiltrated edema from pure vasogenic edema.

Materials and methods

Twenty patients with high-grade glioma and 16 with meningioma or metastatic tumor were enrolled in our study. All cases were confirmed by histopathological study. Diffusion tensor imaging (DTI) was performed in all patients. Peritumoral edema of high-grade glioma was considered tumor-infiltrated edema, and edema of meningioma or metastasis was considered pure vasogenic edema. Fractional anisotropy (FA), mean diffusivity (MD), AD, RD, regression coefficient of RD to AD (RC_RD–AD), and tumor infiltration index (TII) in tumor-infiltrated edema and pure vasogenic edema were analyzed and compared. Receiver operating characteristic (ROC) curve analysis was conducted to demonstrate their differential effectiveness.

Results

RC_RD–AD in tumor-infiltrated edema (0.724 ± 0.125) was significantly higher than that in pure vasogenic edema (0.571 ± 0.111) (P = 0.001). FA of tumor-infiltrated edema (0.175 ± 0.025) was significantly lower than that of pure vasogenic edema (0.203 ± 0.035) (P = 0.007). Other parameters showed no significant difference between the 2 types of edema. ROC curve analysis showed RC_RD–AD was the most effective parameter in distinguishing tumor-infiltrated edema from pure vasogenic edema. Using a threshold of 0.6, a sensitivity of 0.85 and specificity of 0.69 can be achieved with RC_RD–AD.

Conclusion

Analysis of the AD and RD relationship may reflect differences in diffusion characteristics of edema surrounding high-grade glioma and meningioma or metastasis, and may be helpful in detecting peritumoral infiltration in high-grade glioma.     

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。     

脑膜瘤伴周围脑水肿60例分析

目的:研究脑膜瘤伴周围脑水肿的临床与手术特点。方法:本文报道脑膜瘤伴周围脑水肿60例,占同期收治脑膜瘤(130例)的46.2％。对其临床特点、CT、脑血管造影(CAG)与瘤周脑水肿手术所见进行了讨论。结果:CT扫描显示瘤周低密度或部分低密度影为脑膜瘤瘤周脑水肿区。CAG显示该部位血供主要来自颈内动脉软脑膜支,手术所见,在脑膜瘤周围与脑组织软脑膜层之间存在广泛粘连,术中分离肿瘤时出血较多。相反,CT扫描显示肿瘤周围没有低密度改变。CAG检查该部位血供主要来自颈内动脉硬脑膜支,因肿瘤同围无粘连、术中损伤小、出血也少。本组脑膜瘤全切34例,大部切除26例。结论:脑膜瘤瘤周脑水肿产生的重要因素有:①术前肿瘤血运丰富,有软脑膜支供血;②肿瘤周围及脑表面静脉切断后,该处静脉回流不畅,侧支循环在短期内尚未建立。矢状窦旁脑膜瘤手术时要保护上矢窦和中央静脉,对防止术后脑水肿相当重要。应用显微外科技术,可明显提高手术效果。     

脑膜瘤的增殖能力与瘤周脑水肿

目的：探讨脑膜瘤的增殖能力与瘤周脑水肿组的关系。方法：对１３２例脑膜瘤的病理资料用ＷＨＯ的方法进行组织学计分和分级，部分进行了细胞形态计量学（２６例）和流式细胞术（ＦＣＭ）分析（６８例）。结果：中、重度水肿组的组织学计分、分级、肿瘤细胞的细胞密度、核面积及ＦＣＭ的ＤＩ和ＰＩ均高于轻或无水肿组。重度水肿组的超二倍体率及异倍体率均显著高于其它组别。结论：增殖活跃的脑膜瘤易伴中重度瘤周水肿     

An immunocytochemical study of protein clearance in brain infusion edema

Summary The pathways and mechanisms by which edematous fluid accumulation in the extracellular space (ECS) clears from brain are poorly understood. The objective of this study was to explore, using immunocytochemical technique, the fate of a proteinaceous fluid added to the brain ECS and to study the clearance pathways. The protein movement of this edema fluid was investigated using the direct infusion model on rats. Rat albumin (20 l) was slowly infused into the caudate-putamen of anesthetized adult rats and the spread and clearance of the edema was followed in various brain regions using immunocytochemical and conventional light and electron microscopy at 0, 1, 2, 3, 4, 6, and 8 days post-infusion. Our studies showed that protein-rich edema fluid cleared slowly from the brain, with 8 days required for the infusion albumin to exit completely from the brain parenchyma. Immediately following infusion, the albumin was distributed in the ECS of the white matter and the overlying deep cortical layers related to the infusion site. During the next 24 h, more of the infused albumin traveled through the ECS to the cortical surface where the albumin passed through the glia limitans to reach the subarachnoid front. Additionally, at 48 h post-infusion, that albumin, which had migrated to the ventricular wall, cleared from the ECS of the subependymal white matter and the ependymal clefts to reach the ventricular cerebrospinal fluid (CSF). In edematous regions, the perivascular spaces of venules and veins were filled with reaction product. Continuity of this perivascular reaction product existed from the deep edematous area to the temporobasal subarachnoid space from where the reaction product gradually disappeared from the parenchyma. From these studies we infer that during the late state of the resolution process the edema front moves toward both the ventricle and the cortical surface to reach the CSF. Thus, among the potential routes for edema clearance, the pathways leading to CSF clearance of fluid predominated. During this clearance process, neither neurons, glia nor the vascular endothelium showed any endocytotic response to the infused albumin throughout the 8-day course. We conclude from these observations that the CSF pathway is the major route of protein-rich edema clearance, when such clearance is not complicated by any concomitant CNS perturbation.Supported in part by grants NS-19235, NS-20193 and NS-12587 from the National Institutes of Health. Additional facilities and support were provided by the Richard Roland Reynolds Neurosurgical Research Laboratories     

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。