大鼠创伤性颅脑损伤后EPO及受体的表达与意义

目的观察创伤性颅脑损伤大鼠皮层中促红细胞生成素（EPO）及其受体（EPOR）的分布与表达变化,并探讨其意义。方法35只雄性Wistar大鼠,随机分为正常对照组和颅脑损伤后2h、6h、12h、24h、3d和7d共7组,每组各5只。采用Myneurolab脑立体定向仪和Benchmark颅脑损伤撞击器制作创伤性颅脑损伤模型。应用免疫组化和Westernblot分别检测上述时间点损伤灶周围皮层中EPO及EPOR的蛋白表达变化。结果EPO与EPOR广泛表达于神经元、少突胶质细胞和血管内皮细胞中。EPO与EPOR在创伤性颅脑损伤后2h即可见表达增强,6～12h表达继续升高,至24h达高峰,随后EPO的表达开始减弱,而EPOR的表达在24h后持续维持在高水平,无明显降低。结论创伤性颅脑损伤后EPO与EPOR的表达随时间变化不一致。EPOR的持续高水平表达是外源性EPO发挥神经保护作用的分子基础。     

重型颅脑损伤后高钠血症

重型颅脑损伤并发高钠血症较为少见,但预后极差,死亡率高.我科自1999年1月至2002年12月共收治重型颅脑损伤192例,并发高钠血症27例,死亡15例.     

创伤性颅脑损伤后蛋白质组学研究进展

目前蛋白质组学技术被越来越多地应用于发生率及死亡率极高的创伤性颅脑损伤领域。作为研究蛋白质整体水平的重要学科,它以其全面性、高通量等特点,为该病的基础和临床治疗研究提供了新思路与新方法。本文将蛋白质组学技术作为一门方法学对其要点进行介绍,也将其在创伤性颅脑损伤研究领域中的新进展进行综述。     

重型颅脑损伤术后严重脑膨出的原因及治疗

目的探讨重型颅脑损伤术后并发严重脑膨出的原因及治疗方法。方法回顾性分析45例重度颅脑损伤术后并发严重脑膨出的病例。结果36例治愈出院,5例重残,2例因颅内感染死亡,2例因并发肺部感染死亡。结论重型颅脑损伤术后并发严重脑膨出的原因主要是严重挫伤后脑水肿、弥漫性脑肿胀、脑积水和颅内感染。有效运用药物和采取各项措施减轻脑水肿,解除脑积水,预防感染是解决重度颅脑损伤术后并发顽固性脑膨出的有效方法。     

颅脑损伤后免疫状态的改变

重型颅脑损伤后,患者的全身及脑组织局部免疫状况均会发生一系列改变.免疫功能下降导致临床上各型感染几率增加,而免疫功能不适当的激活又可导致全身炎症反应综合征及神经元继发性损伤.     

重型颅脑损伤后颅内压、脑灌注压变化及意义

重型颅脑损伤后颅内压、脑灌注压变化及意义张文德章翔易声禹刘卫平王立根顾建文宋少军梁景文一、材料与方法１．对象：５０例重型颅脑损伤，ＧＣＳ３～８分作为监护组。男３８例，女１２例，年龄４～６９岁，平均３４．６岁。５０例中保守治疗１０例，手术４０例，二次手...     

神经元机械性损伤后Homer蛋白表达及意义

目的研究体外培养神经元机械损伤后不同亚型Homer蛋白表达的变化规律,进一步阐明Homer与神经元损伤的关系.方法胎鼠脑皮质神经元体外培养7 d,以微量移液器塑料滴头划割培养的神经元,横、竖各划8道,划伤宽度约1 mm,造成机械性损伤.在伤后不同时间(10、30 min,1、3、6、12、24、72 h),采用链酶亲合素-过氧化物酶复合物法(SABC法)行免疫组化染色.对照组不进行机械性划割,其它处理同损伤组.结果对照组神经元在各时间点Homer 1a免疫组化染色呈弱阳性.机械性损伤后从伤后10 min持续至24 h Homer 1a表达量增加,免疫组化染色呈阳性.阳性染色呈颗粒状分布于胞浆、胞膜及突起.Homer 1b/c,Homer 2a/b和Homer 3在对照组神经元中即有一定程度表达,机械性损伤后,其表达量无明显变化.结论神经元机械性损伤后Homer 1a表达明显升高,而Homer 1b/c、2a/b和3表达无明显变化. Homer 1a对第1组代谢型谷氨酸受体(mGluR)的功能具有负反馈作用,Homer 1b/c、2a/b和3则调节mGluR在细胞表面的分布,提高其稳定性.据此推测,增加Homer 1a表达或减少Homer 1b/c、2a/b和3的表达可能改变mGluR受体信号的传递效率,对神经元具有保护作用.     

重型颅脑损伤后肺水肿的治疗分析

目的 探讨重型颅脑损伤后肺水肿的诊断和治疗.方法 对132例重型颅脑损伤后肺水肿患者的临床资料进行回顾性分析,对其分类、发病原因、诊断及治疗方法进行探讨.结果 132例患者经抢救治疗,成活76例,死亡56例.结论 重型颅脑损伤后肺水肿的死亡率较高,早期诊断和及时治疗是抢救成功的关键.     

急性颅脑损伤后血清甲状腺素的改变及其意义

目的探讨急性颅脑损伤后血清甲状腺素水平的改变及其意义。方法应用磁性酶联免疫定量分析法检测１５６例急性颅脑损伤患者伤后２４～７２小时及存活者伤后２周的血清Ｔ３、游离Ｔ３（ＦＴ３）、Ｔ４、游离Ｆ４（ＦＴ４）及促甲状腺激素（ＴＳＨ）水平的改变,并与１００名正常对照者比较。结果伤后患者早期血清Ｔ３、ＦＴ３水平显著降低（Ｐ〈０．００１）,而Ｔ４、ＦＴ４显著升高（Ｐ〈０．０１）;颅脑损伤愈重,昏迷程度愈深,上     

重型颅脑损伤后尿崩症的临床分析

目的探讨重型颅脑损伤后尿崩症的病因及治疗方法。方法47例颅脑损伤后尿崩症患者,根据尿崩症状轻重给予双氢克尿噻鼻饲、垂体后叶素皮下注射、长效尿崩停肌注,酌情应用改善微循环药物。结果治疗4周后,4例患者尿崩症状用双氢克尿噻控制,25例用垂体后叶素或弥凝控制,11例用长效尿崩停控制,7例死亡。随访半年,30例治愈,10例未愈,需口服弥凝维持。结论颅脑损伤后尿崩症与下丘脑垂体原发性或继发性损害有关,GCS3～5分、急性尿崩症患者预后差。     

大鼠颅脑损伤后钠通道α亚单位1.3（Nav1.3）在海马中的表达

目的研究颅脑损伤（TBI）后钠通道α亚单位1.3（Nav1.3）的mRNA和蛋白在海马中的表达情况。方法对成年SD大鼠实施脑液压伤后,在伤后2h、12h、24h和72h处死,取伤侧海马行荧光定量PCR和Western blot检测Nav1．3的mRNA和蛋白表达情况,通过免疫荧光染色检On,0Nav1．3在海马的表达特点。结果大鼠脑液压伤后Nav1.3的mRNA表达显著上调（P〈0.01）,伤后12h其上调达最高水平,而Nay1.3蛋白的表达也在相同时间段出现显著上调（P〈0．01）。免疫荧光染色显示Nav1.3在海马主要表达于神经元细胞。结论TBI可导致Nav1.3的mRNA和蛋白表达显著上调,这可能是TBI后神经元细胞膜上钠通道功能异常及其诱发兴奋性毒性作用的分子学基础之一。     

大鼠弥漫性颅脑损伤后脑红蛋白mRNA变化的实验研究

目的研究弥漫性颅脑损伤后大鼠脑组织中脑红蛋白（NGB）mRNA的表达变化情况，初步探讨NGB与颅脑损伤的关系。方法选择Marmarou自由落体打击装置制作弥漫性颅脑损伤模型．采用实时、定量PCR检测伤后不同时间脑组织中NGB mRNA的表达情况，并对所得数据进行统计学分析。结果在伤后30min，脑组织中NGB mRNA的表达出现首个高峰．此后逐渐下降，至6h恢复至正常水平；伤后12h再次升高，于伤后48h达高峰，此后下降，至伤后5d仍高于正常水平。结论弥漫性颅脑损伤后，脑组织中NGB mRNA表达呈“双峰”，提示其可能参与神经元损伤后应激及继发缺血、缺氧性脑损害的应答机制。     

Neuroglobin expression in rats after traumatic brain injury

In this study,we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin,brain injury and neuronal apoptosis.Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex,and peaked at 30 minutes and 48 hours following traumatic brain injury.Immunohistochemical staining demonstrated that neu-roglobin expression increased and remained high 2 hours to 5 days following injury.The rate of in-crease in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury.Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased,while that of the proapoptotic factor decreased,in the cerebral cortex post severe closed traumatic brain injury.It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.     

Increased expression of AGS3 in rat brain cortex after traumatic brain injury

Receptor‐independent activators of G protein signaling (AGS) offer alternative modes of signal processing for the G protein signaling system that has broad mechanistic and functional significance. Previous studies have demonstrated that AGS3, which belongs to the AGS family, is involved in a number of different cellular activities. However, the distribution and function of AGS3 in the central nervous system (CNS) remain unclear. To investigate whether AGS3 is involved in CNS injury and repair, we used an acute traumatic brain injury (TBI) model in adult rats. Western blot analysis and immunohistochemistry showed a significant upregulation of AGS3 in ipsilateral peritrauma cortex. Double immunofluorescence staining showed that AGS3 was coexpressed with NeuN but rarely with glial fibrillary acidic protein. In addition, we detected that active caspase‐3 had colocalization with NeuN and AGS3, suggesting that AGS3 might be involved in the neuron apoptosis after TBI. To investigate the potential function of AGS3 further, a neuronal cell line, PC12, was employed to establish a cell apoptosis model. Western blot analysis indicated that AGS3 shared a similar dynamic variation in animal experiments, and phosphorylated cyclic AMP response element‐binding protein (CREB) increased in parallel. Additionally, knocking down AGS3 with siRNA partially attenuated the protein level of phosphorylated CREB in PC12 stimulated by H₂O₂, while reinforcing active caspase‐3 expression, demonstrating a probable antiapoptotic role through CREB played by AGS3 in neuronal apoptosis. We hypothesize that AGS3 might play an important antiapoptotic role through enhancing phosphorylation of CREB. © 2013 Wiley Periodicals, Inc.     

持续有创颅内压监测对重型颅脑损伤病人救治的临床意义

目的研究重型颅脑损伤病人术后行有创动态颅内压监测的临床意义。方法回顾性分析158例行手术治疗的重型颅脑损伤病例资料,随机分为颅内压监测组与对照组,每组79例。比较两组脱水剂使用剂量、并发症发生率及GOS评分。结果与对照组比较,颅内压监测组甘露醇使用时间和剂量显著减少,而肺部感染、电解质紊乱的发生率明显降低(均P0.01)。两组GOS评分差异具有统计学意义(P0.01)。结论持续有创颅内压监测可及时反映颅内压变化,对病人临床救治及判断预后有积极的指导意义。     

Dysautonomia after severe traumatic brain injury

Background: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. Methods: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) ≤ 8 on admission]. Results: Seventy‐six of 119 patients survived and were eligible for follow‐up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3–68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92–83.33] and the development of spasticity (RR 16.94, CI 3.96–71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. Conclusions: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow‐up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism.     

r—HuEPO对外伤性脑损伤大鼠凋亡基因表达的影响

目的探讨重组人促红细胞生成素（r—HuEPO）对外伤性脑损伤大鼠凋亡基因表达的影响。方法将48只健康成年雄性SD大鼠随机分成4组：r-HuEPO1000U／kg、3000U／kg、5000U／kg治疗组和生理盐水对照组。采用改良的Feeney氏法制作大鼠自由落体脑创伤模型,r—HuEPO干预。一周后麻醉取脑冻存：免疫组织化学法测定脑组织中NF—κB、C-myc和Fas／Fasl的阳性细胞及凋亡细胞数。结果与对照组相比,各组中NF—KB、Fas和Fasl阳性细胞及凋亡细胞数均有显著减少（P〈0．05）,尤其是5000U／kgr—HuEPO组减少最显著（P〈0．01）。结论r—HuEPO可抑制创伤性脑损伤大鼠NF—KB、Fas／Fasl的促凋亡作用,减轻迟发性神经元损伤,从而起到神经保护的作用。     

硫氧还蛋白还原酶 TrxR2在颅脑损伤大鼠皮质的表达变化

目的：探究硫氧还蛋白还原酶2（TrxR2）在颅脑损伤大鼠皮质的动态表达变化。方法54只雄性 SD 大鼠,随机分为正常对照组（n =6）和颅脑损伤组（n =48）。颅脑损伤组采用改良的 Freeny＆#39;s 自由落体装置制作颅脑损伤大鼠模型,正常对照组不做处理。伤后1 h、3 h、6 h、12 h、24 h、3 d、7 d、14 d,采用实时荧光定量 PCR （quantitative real-time PCR,qRT-PCR）和Western blot 检测挫伤区周围皮质 TrxR2 mRNA 和蛋白的表达变化情况。结果 qRT-PCR 结果显示：皮质中 TrxR2 mRNA 颅脑损伤后1 h 表达增加,24 h 达到高峰,7 d 恢复正常;颅脑损伤组伤后1 h~3 d 各时间点 TrxR2 mRNA 表达明显高于正常对照组（均 P ＜0.05）。Western blot 检测显示：TrxR2蛋白在颅脑损伤后1 h 表达增加,24 h 达到高峰,14 d 恢复正常;颅脑损伤组1 h~7 d 各时间点 TrxR2蛋白表达高于正常对照组（均 P ＜0.05）。结论颅脑损伤后 TrxR2表达增多,提示 TrxR2作为一种急性应激反应蛋白参与颅脑损伤早期抗氧化应激反应。     

颅脑损伤后冷环境下神经细胞凋亡及相关蛋白表达

目的 探讨冷环境下大鼠颅脑损伤后神经细胞凋亡及相关蛋白Bcl-2,Bax的表达.方法 80只健康SD大鼠随机分为冷环境致伤组、常温致伤组、冷环境对照组和常温对照组,每组20只;致伤组以撞击法制作重型颅脑损伤模型,对照组仅行开颅手术.采用免疫组化法检测各组神经细胞凋亡及凋亡蛋白Bcl-2,Bax的表达;比较各组大鼠的体温变化、凋亡细胞及凋亡蛋白阳性率差异.结果 冷环境致伤组致伤后大鼠体温显著下降.不同致伤组致伤后凋亡细胞阳性率均显著增加,且两组同时间段比较存在显著差异(P <0.05).不同致伤组致伤后凋亡蛋白Bcl-2,Bax表达均增高,两组同时间段Bax表达差异有统计学意义(P <0.05);冷环境致伤组Bax/Bcl-2比值明显高于常温致伤组(P <0.05).结论 冷环境可引起颅脑损伤后大鼠体温降低,促进神经细胞凋亡.     

An analysis of communication in conversation after severe traumatic brain injury

Background and objective: Communication disorders have been reported following severe traumatic brain injury. However, we have little information about patient behaviour during dyadic interaction. Here, we analyzed conversation at the rehabilitation and chronic phase post traumatic brain injury (TBI), to define the main mechanisms of verbal and non‐verbal communication disorders and relationship with other cognitive difficulties. Methods: Sixteen patients were evaluated at the rehabilitation phase (2–12 months) and 18 at the chronic phase (after 2 years) following severe TBI. They were compared with equivalent groups of matching (gender, age, education level) control subjects. We used the Lille Communication Test, which comprises three parts: participation to communication (greeting, attention, engagement), verbal communication (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics, verbal feedback) and non‐verbal communication (understanding gestures, affective expressivity, producing gestures, pragmatics, non‐verbal feedback). We also investigated executive functions (Stroop test, trail‐making test, categorical evocation), language (Montreal‐Toulouse protocol) and behaviour (Neurobehavioural Rating Scale). Verbal communication disorders were relatively equivalent at the rehabilitation and chronic phases. Results: Patients were impaired (P ≤ 0.01) in their participation to communication, especially in greeting behaviour. Verbal communication was mostly affected by difficulties in producing fluent and intelligible language and using pragmatics (responding to open questions, presenting new information and introducing new themes, organizing discourse and adapting to interlocutor knowledge). Non‐verbal communication was impaired by difficulties in using pragmatics (mostly adapted prosody). Participation and verbal communication correlated with the executive functions, language and behavioural assessment. Conclusions: Disorders of social communication justify systematic assessment in patients with TBI.