Expression of nestin after traumatic brain injury in rat brain

We tested the hypothesis that traumatic brain injury upregulates expression of nestin, an embryonic cell intermediate filament protein. Brain from rats (n=24) subjected to controlled cortical impact injury and sham operated (n=3) and normal (n=3) rats were processed for dual label immunohistochemical study to identify cellular expression of nestin. Our results show that in normal noninjured animals, nestin is expressed slightly and localized only in a few endothelial and subventricular cells. In contrast, at 1–4 weeks postinjury nestin is strongly expressed in astrocytes and microglia. The expression of nestin in astrocytes and microglia after traumatic brain injury support the hypothesis that injured cerebral tissue expresses developmental proteins, and that these proteins may promote recovery after injury.     

小胶质细胞在颅脑外伤后胶质瘢痕形成中的实验研究

目的研究小胶质细胞在颅脑外伤后胶质瘢痕形成中的作用。方法选取8~10周龄SD大鼠48只,雌雄各半。按体质量相近原则,随机分为观察组和对照组,观察组建立大鼠颅脑外伤模型,对照组不作任何处理,正常饲养。分别在造模后1d和7d收集各组大鼠的血液,检测血清中TNF?α、IL-1β、IL-6、IL-4以及IL-10表达量,并进行统计分析,并于2组造模后1d、7d分别取每组12只大鼠大脑组织进行病理检查,观察颅脑外伤后胶质瘢痕的形态学。结果观察组造模1d血清中TNF?α、IL-1β、IL-6、IL-4以及IL-10的表达量分别为79.8±8.7、83.6±8.3、83.3±10.2、83.3±7.8以及82.7±6.8。对照组饲养1d血清中TNF?α、IL-1β、IL-6、IL-4以及IL-10的表达量分别为69.3±7.2、68.6±7.4、71.4±7.3、69.5±7.6以及65.4±8.6。观察组造模7d后血清中TNF?α、IL-1β、IL-6、IL-4以及IL-10的表达量分别为96.8±12.4、92.6±11.2、96.8±12.2、95.8±12.5以及90.4±12.2。对照组饲养7d后,血清中TNF?α、IL-1β、IL-6、IL-4以及IL-10的表达量分别为82.1±9.5、70.3±6.8、82.2±12.6、82.2±8.6以及67.1±6.4。观察组TNF?α、IL-1β、IL-6、IL-4以及IL-10的表达量明显高于对照组,差异有统计学意义(P0.05)。结论小胶质细胞在颅脑外伤后胶质瘢痕形成中具有双重作用,小胶质细胞激发后可产生TNF?α、IL-1β、IL-6、等炎症因子,又同时可以释放L-4以及IL-10等抑制炎症反应的因子。干预小胶质细胞的活化,抑制炎症反应因子的释放,可有效预防颅脑外伤后胶质瘢痕形成,同时,也能指导临床治疗颅脑外伤后胶质瘢痕形成。     

Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a “reactive” state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed ‘satellite microglia’). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury.     

颅脑外伤对患者智能状况的影响及相关因素研究

目的：研究颅脑外伤对患者智能状况的影响,探讨与之相关的生物、心理、社会因素。方法：本研究对63例急性期颅脑外伤患者,采用标准化测评工具,包括《格拉斯哥昏迷评分（GCS）》、《简易智力状态检查》、《数字划消测验》、《社会支持评定量表》、《日常生活能力量表》及自制颅脑外伤患者人口学与相关因素调查表等,逐例进行现场临床测评,将拟分析的因素进行量化,最后将汇总的资料进行整理,分析、总结。所有统计分析均使用SAS软件包完成。结果：颅脑外伤患者智能缺陷的发生率为71．43％,其显著性差异表现在文化程度、治疗措施及手术类型三个方面,主要影响因素有外伤程度、外伤部位、社会支持、文化程度及治疗措施。结论：不同外伤类型的颅脑外伤对患者的智能状 况产生不同程度的影响,其相关因素包括生物、心理、社会学三个方面,基础的生物学病因虽然对智能起决定作用,而社会心理因素的影响仍不可忽视。     

重型颅脑损伤后并发精神障碍临床分析

目的回顾分析重症颅脑损伤后并发精神障碍。方法总结我院1998-10~2006-10收治的重症颅脑损伤后并发精神障碍46例病人,分析伤情、受伤部位与并发的精神障碍间的关系。结果本组病人共出现4型精神障碍:躁狂型、抑郁型、精神分裂样型、痴呆型。损伤部位分别为:额叶损伤、颞叶损伤、胼胝体损伤、脑干损伤。损伤类型为:脑挫伤、弥漫性轴索损伤(DAI)、脑挫伤并发颅内血肿或并发脑疝。结论额叶脑挫伤或颞叶脑挫伤并发躁狂型精神障碍最多见,脑干损伤及DAI常出现痴呆型精神障碍。     

颅脑外伤患者的抑郁症状及相关因素研究

目的：研究颅脑外伤后患者的抑郁症状及相关因素,方法：对63例急性期颅脑外伤患者,采用标准化测评工具,包括《格拉斯哥昏迷评分（GCS）》,《汉密顿抑郁量表（HRSD）》,《社会支持评定量表》,《日常生活能力量表》及自制颅脑外伤患者人口学与相关因素调查表等。逐例进行现场临床测评,汇总资料进行整理,分析,所有统计分析均使用SAS软件包完成。结果。颅脑外伤患者抑郁症状的发生率为42．86％,其中,重度,中度,轻度抑郁的发生率辚3．17％,7．93％,31．74％,不同外伤类型,年龄,性格,外伤原因及患者对外伤持不同态度的颅脑外伤患者抑郁症状的发生率存在显著性差异,主要影响颅脑外伤后抑郁症状的因素有外伤程度,性格,社会支持,病理征及年龄。结论：提示除了外伤的生物学影响外,抑郁的发生与患者个体的生理心理特点和社会环境因素密切相关。     

Neural correlates of self-evaluative accuracy after traumatic brain injury

Individuals who have sustained a traumatic brain injury (TBI) often exhibit an array of cognitive deficits, yet perhaps most maladaptive of these sequelae is the frequent occurrence of reduced insight into one's own condition. In such cases, TBI individuals may overestimate their post-injury level of socio-cognitive functioning, leading to disparities between how they perceive themselves and what others observe. This functional MRI (fMRI) investigation examined the relationship between level of insight into one's post-injury condition (i.e. trait/ability status) and neural activation evoked during an fMRI task involving self-appraisal of one's traits and abilities. Twenty TBI patients (8-12 weeks post-injury, ER Glasgow Coma Scale Average = 10.9+/-2.8) were selected on the criterion that they overestimate their current trait/abilities (as detected on the patient competency rating scale, PCRS). fMRI activation on the self-appraisal task was compared between the TBI patients and 20 matched controls. For both groups, the fMRI task evoked activation at mid-line prefrontal and retrosplenial cortices. TBI patients exhibited greater signal change in the anterior cingulate, precuneus and right temporal pole. Subsequently, a linear regression analysis was conducted for the TBI group, with the PCRS and a measure of cognitive speed entered as predictor variables to determine the selective effect of insight on self-evaluative brain activation. A more accurate level of trait/ability-based insight was related to increased signal change in the right anterior dorsal prefrontal cortex (PFC). The results suggest that one's post-injury level of self-referential insight is related to a network inclusive of the medial and right dorsal PFC.     

创伤性脑损伤后大鼠海马区糖皮质激素受体mRNA的表达

目的研究创伤性脑损伤(TBI)后大鼠海马区糖皮质激素受体(GR)mRNA表达的变化及其对大鼠认知功能的影响。方法建立大鼠头颅侧向旋转加速脑创伤模型,应用逆转录酶-聚合酶链式反应(RT-PCR)和Morris水迷宫检测伤后大鼠海马区GR mRNA的表达与学习记忆功能的关系。结果伤后4～7 d大鼠海马区GR持续低表达;Morris水迷宫检测伤后大鼠出现认知功能障碍。结论 TBI大鼠海马区GR mRNA的降低影响大鼠认知功能。     

颅脑创伤后凝血功能障碍的研究进展

颅脑创伤作为一种常见的创伤类型,给社会以及家庭造成了沉重的负担。凝血功能障碍在颅脑创伤后十分常见,尤其多见于服用了抗凝或抗血小板聚集药物的患者。颅脑创伤后凝血功能障碍的发生机制复杂,并且没有统一的诊断标准,但是其出现往往导致进展性颅内出血的发生,严重影响患者预后。成分输血以及相关血液制品和止血药物的应用是目前纠正颅脑创伤后凝血功能障碍的主要治疗手段。本文将对颅脑创伤后凝血功能障碍的发生机制、诊断和治疗的研究现状做一综述。     

Identity,grief and self-awareness after traumatic brain injury

The objective of this study was to investigate perceived identity change in adults with traumatic brain injury (TBI) and explore associations between identity change, grief, depression, self-esteem and self-awareness. The participants were 29 adults with TBI who were being followed up by a community brain injury rehabilitation service. Participants were longer post-injury than those more commonly studied. Time since injury ranged from 2.25 to 40 years (mean?=?11.17 years, SD?=?11.4 years). Participants completed a battery of questionnaires. Significant others and clinicians completed a parallel version of one of these measures. Questionnaires included the Head Injury Semantic Differential Scale (HISDS-III), Brain Injury Grief Inventory (BIGI), Hospital Anxiety and Depression Scale – Depression, Rosenberg Self-Esteem Scale (RSES) and the Awareness Questionnaire (Self/Significant other/Clinician versions). The main findings were that participants reported significant changes in self-concept with current self being viewed negatively in comparison to pre-injury self. Perceived identity change was positively associated with depression and grief and negatively associated with self-esteem and awareness. Awareness was negatively associated with self-esteem and positively associated with depression. These findings were consistent with previous research, revealing changes in identity following TBI. Further research is needed to increase our understanding of the psychological factors involved in emotional adjustment after TBI and to inform brain injury rehabilitation interventions, including psychotherapy approaches.     

多奈哌齐与安慰剂治疗脑外伤后记忆障碍的对照研究

目的　探讨多奈哌齐治疗脑外伤后记忆障碍的有效性和安全性。方法　对59 例脑外伤病人随机分成两组,分别给予口服多奈哌齐与安慰剂治疗6个月,采用WMS评价临床疗效,定期查体和实验室检查评价药物不良反应。结果　治疗后多奈哌齐组WMS各项评分均有显著提高(P<0.01~0.05),与安慰剂比较,WMS评分长时记忆、瞬时记忆、记忆商有统计学差异(P<0.05)。口服多奈哌齐未见严重药物不良反应。结论　多奈哌齐治疗脑外伤后记忆障碍有效,安全性好。。     

脑外伤后进展性出血性脑损伤的诊治体会

目的研究脑外伤后进展性出血性脑损伤的临床特点,总结其发病机制,探讨及时诊断、治疗的方法。 方法回顾性分析解放军第二五一医院神经外科自2015年1月至2017年6月收治的167例脑外伤后进展性出血性脑损伤患者的临床资料。本组患者入院时按GCS评分：3~5分11例,6~8分36例,9~12分83例,13~15分37例。临床表现均有不同程度的颅高压症状,观察治疗过程中,76例患者出现意识障碍或意识障碍加深,94例患者肢体肌力减退,81例患者频繁呕吐,43例患者躁动,5例患者脑疝。 结果手术治疗94例,保守治疗73例。所有患者依据GOS评分判断：恢复良好114例,中残32例,重残13例,死亡8例（4.8%）。 结论动态CT观察是早期发现进展性出血性脑损伤的有效方法。对外伤性颅内血肿的患者绝不能仅仅依赖首次CT结果即制定一成不变的治疗方案,应进行专科监测和动态CT观察,根据患者血肿量的变化及时调整治疗方案。     

Sex-dependent effects of GPER activation on neuroinflammation in a rat model of traumatic brain injury

The G protein-coupled estrogen receptor (GPER) plays a role in estrogen-mediated neuroprotection and has been considered a potential therapeutic target for treating various neurological diseases. It is increasingly recognized that sex is a biological variable affecting treatment outcomes and efficacy, and that neuroinflammation is a key secondary injury mechanism following brain injury, though it is unknown whether the neuroprotective effects exerted by GPER involve modulation of inflammatory processes. The aim of this study was to investigate whether activation of GPER has a sex-dependent effect on neuroinflammation following traumatic brain injury (TBI), a sexually dimorphic disease. In male and ovariectomized (OVX) female rats, the GPER agonist, G1, inhibited the upregulated expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), increased the expression of the anti-inflammatory cytokine IL-4, and shifted microglia/macrophage polarization toward the M2 phenotype. In gonadally-intact females, G1 caused more pro-inflammatory (IL-6 and TNF-α) and less anti-inflammatory cytokine (IL-4) production, without altering microglia/macrophage polarization. Estradiol supplementation blocked the effects of G1 in OVX females. We also found that post-injury GPER expression was increased in males and OVX females but not in intact females. G1 administration increased Akt phosphorylation in males and OVX females, but had no significant effect in intact females, while Akt inhibition blocked the effects of G1 in males and OVX females. These results indicate that G1 exerts anti-inflammatory effects in males and OVX females but not in intact females; these sex-specific effects are dependent on circulating estrogen levels and are partially mediated through Akt signaling. Future studies are needed to elucidate the relevant molecular mechanisms, especially in females. A better understanding of the sex differences in treatment efficacy with GPER agonists may help improve personalized therapeutic strategies for males and pre- and postmenopausal females with TBI.     

创伤性颅脑损伤后脑组织中TLR4表达的实验研究

目的 研究创伤性脑损伤(TBI)后损伤灶周围脑组织Toll样受体4(TLR4)的表达,探讨TLR4/NF-κB信号通路在TBI中的作用机制.方法 SD大鼠36只按随机数字表法分为对照组(n=12)、TBI后1d组(n=6)、TBI后3d组(n=12)和TBI后7d组(n=6),后3组采用Feeney自由落体撞击法制作TBI模型,对照组仅行右侧顶部开窗而无TBI.应用RT-PCR、凝胶电泳迁移率实验(EMSA)、ELISA分别检测4组大鼠挫伤脑组织TLR4 mRNA、NF-κB活性、TNF-α和IL-6浓度的变化;免疫组化染色检测对照组和TBI后3d组大鼠挫伤脑组织TLR4的表达.结果 与对照组比较,TBI后1d、3d、7d组TLR4 mRNA表达、NF-κB活性、TNF-α和IL-6浓度均增加,差异有统计学意义(P＜0.05);对照组脑组织TLR4表达较少,TBI后3d组创伤灶周围可见大量TLR4阳性细胞,主要表达在皮层胶质细胞、神经元中;NF-κB活性与TLR4 mRNA的表达呈正相关关系(r=0.786,P=-0.000).TNF-α、IL-6与TLR4的表达也呈正相关关系(r=0.517,P=0.010;r=0.503,P=0.012).结论 TBI可引起损伤区脑组织TLR4的表达和下游NF-κB、促炎症因子水平的增加,TLR4/NF-κB信号通路可能在脑组织的继发性损害中起重要作用.     

锌对脑外伤后神经元中泛素化蛋白表达的影响

目的 研究脑外伤(TBI)后锌和泛素化蛋白在神经元中的变化,探讨锌在脑外伤后继发性神经损伤中的作用机制.方法 建立重物坠落致脑外伤动物模型,应用ZP4荧光染色、Western blot法分别观察神经元中锌及泛素化蛋白变化,用Nissle染色检测神经元存活数目;最后在脑外伤患者挫伤区神经元中分别用AMG染色、Western blot法分别检测锌及泛素化蛋白变化.结果 ZP4荧光染色、Western blot法和Nissle染色发现脑外伤可诱导大鼠海马神经元中锌聚集、泛素化蛋白升高以及最终导致神经元损伤;而阻断锌聚集可减少神经元中泛素化蛋白的升高,并产生神经保护作用.最后,在人脑外伤挫伤区神经元中,应用AMG染色和Western blot法也检测到了明显锌聚集和泛素化蛋白的升高.结论 脑外伤后锌稳态的失衡可以影响蛋白质的降解并最终导致神经元的损伤.     

大鼠颅脑创伤后脑红蛋白表达变化的实验研究

目的研究弥漫性颅脑创伤后大鼠脑组织中脑红蛋白的核酸与蛋白表达变化情况，初探脑红蛋白与颅脑创伤的关系。方法选择Marmarou’s自由落体打击装置复制弥漫性颅脑创伤模型，采用实时定量PCR及Westernblotting分别检测伤后不同时间（30min、1h、2h、6h、12h、24h、48h、72h、5d）脑组织中脑红蛋白核酸及蛋白水平的表达情况，并对所得数据进行统计学分析。结果在伤后30min，脑组织中脑红蛋白的核酸表达m现首个高峰，相应地其蛋白表达于伤后1h增高，于伤后2h达峰值；伤后12h，脑红蛋白的核酸表达再次升高，于伤后48h达高峰，其蛋白表达亦于伤后24h增高，至72h达峰值。结论颅脑创伤后脑组织中脑红蛋白呈“双峰”样表达。提示脑红蛋白可拮抗对神经元的创伤应激及伤后继发缺血、缺氧性损害，对创伤后脑组织具有一定的保护作用。     

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。     

A transdiagnostic investigation of emotional distress after traumatic brain injury

Emotional distress after traumatic brain injury (TBI) often presents as a range of neurobehavioural and emotional reactions rather than distinct disorders. This study adopted a transdiagnostic approach with the aim of identifying psychological processes common to depression, anxiety and global distress after TBI. Fifty participants with TBI (aged 19–66 years, 12–65 months post-injury) completed measures of threat appraisals and avoidance behaviour (Appraisal of Threat and Avoidance Questionnaire), self-discrepancy (Head Injury Semantic Differential Scale III), emotion dysregulation (Difficulties in Emotion Regulation Scale), worry (Penn State Worry Questionnaire), negative self-focused attention (Self-Focus Sentence Completion) and emotional distress (Depression Anxiety Stress Scales and Brief Symptom Inventory). Significant correlations were found among the proposed transdiagnostic variables (rs?=?.29–.82, p?sr²?=?.12–.17). Such findings indicate the need for interventions to target difficulties in identifying and regulating emotions after TBI to facilitate emotional adjustment.     

RIP1/3对创伤性脑损伤后神经元的作用及其机制研究

目的 探讨RIP1/3对创伤性脑损伤(TBI)后神经元的影响及其作用机制。方法 将体外培养的皮层神经元分为4组:siRIP组、Nec-1预处理组、阴性质粒转染组和对照组。通过慢病毒转染法分别干涉RIP1、RIP3表达,建立离体TBI损伤模型,通过流式细胞学检测划伤后神经元存活情况。对体外培养的皮层神经元敲除RIP1/3,建立谷氨酸诱导神经元损伤模型,通过流式细胞学检测谷氨酸刺激后神经元存活情况。结果 siRIP组及Nec-1预处理组机械性损伤后神经元存活率高于阴性质粒转染组和对照组。Nec-1预处理组谷氨酸损伤后神经元存活率高于对照组,而siRIP组存活率与对照组和阴性转染组比较未见显著差异。结论 RIP1和RIP3可能对TBI诱导后神经元死亡有作用,而RIP1抑制剂Nec-1可能对TBI具有脑保护作用。RIP1/3与谷氨酸兴奋毒性诱导细胞死亡无关,而Nec-1对于谷氨酸损伤具有潜在保护作用,并可能存在特异性靶点。