脑微损伤的影像学进展

脑微损伤是创伤性脑损伤最常见的类型,然而,其潜在的神经生理机制尚未完全阐明,影响患者的早期诊断、治疗及预后评估。近年来,多项磁共振（MRI）新技术不断地涌现并用于评估脑微损伤,如功能磁共振、灌注MRI、弥散张量成像、定量易感性图谱、T2 mapping等。本研究综述了多模态MRI在脑微损伤中的应用,从不同的角度深入地了解脑微损伤的神经病理机制,有助于提高临床医生对脑微损伤的诊断和治疗。     

长时程亚低温治疗对重度颅脑损伤患者脑损伤标志物及氧化应激指标的影响

目的:探讨长时程亚低温治疗对重度颅脑损伤患者脑损伤标志物及氧化应激指标的影响。方法:62例重度颅脑损伤患者根据治疗方式不同将其分为短时程（2 d）亚低温治疗组（对照组, n=30）和长时程（5 d）亚低温治疗组（观察组, n=32）,治疗后第6天时比较两组患者凝血功能指标、脑损伤标志物、氧化应激指标、并发症发生情况,随访期间观察患者昏迷时间及30 d致残率与30 d病死率。结果:治疗后第6天时,观察组血清凝血酶原时间、凝血酶时间、活化部分凝血酶原时间水平高于对照组（P<0.05）,观察组血清D-二聚体水平低于对照组（P<0.05）。治疗后第6天时,观察组患者血清髓鞘碱蛋白、神经元特异性烯醇化酶、S100蛋白、丙二醛、超氧化物歧化酶水平均低于对照组（P<0.05）。两组患者颅内血肿、胃肠动力减弱、泌尿系感染、肺部感染、应激性溃疡发生率无统计学差异（P>0.05）。观察组患者昏迷时间较对照组缩短（P<0.05）;观察组患者30 d致残率及30 d病死率均低于对照组,但两组间差异无统计学意义（P>0.05）。结论:长时程亚低温治疗有利于改善重度颅脑损伤患者凝血功能,降低脑损伤标志物水平及氧化应激损伤,缩短昏迷时间,且不增加并发症发生风险。     

大鼠创伤性脑损伤后星形胶质细胞的变化

目的：探讨大鼠创伤性脑损伤后星形胶质细胞的形态学变化及GFAP和NOS的表达情况。方法：采用大鼠自由落体脑损伤模型，伤后1、3、7d取脑切片，行Nissl染色以及GFAP免疫组化和NADPH—d组化单标记及双标记染色。结果：损伤区周围皮质GFAP阳性细胞胞体增大、突起增粗增长，GFAP阳性细胞数量与正常侧及对照组相比，伤后1d即有明显增加，伤后3d、7d数量持续增加；损伤侧海马CAI～3区和DG各层GFAP阳性细胞排列紊乱，胞体增大、突起增粗增长，GFAP阳性细胞数量与正常侧及对照组相比则无明显变化。损伤区周围皮质、损伤侧海马NOS阳性细胞数量明显增加。伤后3d损伤区周围皮质和损伤侧海马中GFAP与NOS双标细胞分别占GFAP阳性细胞的14．2％和13．4％左右。结论：大鼠创伤性脑损伤后大量的星形胶质细胞活化、GFAP表达增加并且部分转化为NOS阳性细胞，提示其参与了脑组织的损伤与修复过程。     

脑外伤小鼠海马血管内皮生长因子表达的变化

目的探讨脑外伤小鼠海马血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的变化。方法 40只Balb/c小鼠随机分为2组,假手术组(10只)和脑外伤组(30只)。脑外伤组依据脑外伤的不同时间点再分6h、1d、3d三个小组,每组10只。免疫组化和Western blot检测各组小鼠海马VEGF蛋白的表达。RT-PCR方法检测各组小鼠海马VEGF mRNA的表达变化。结果免疫组化和Western blot结果发现,脑外伤组小鼠海马VEGF蛋白表达量明显高于假手术组(<0.05);RT-PCR结果也发现,脑外伤组小鼠海马VEGF mRNA表达量明显高于假手术组(<0.05)。结论脑外伤小鼠海马VEGF表达明显升高。     

大鼠创伤性脑损伤后细胞凋亡及NOS阳性细胞的变化

目的：探讨大鼠创伤性脑损伤后不同时相皮质、海马、隔区细胞凋亡及NOS、ChAT阳性细胞的变化。方法：采用大鼠自由落体脑损伤模型，伤后1、2、3、4、5、7、10d取脑切片，经Nissl染色，用TUNEL法检测细胞凋亡，NADPH—d组化染色观察NOS阳性细胞，ChAT免疫组化染色观察隔区ChAT阳性细胞。结果：Nissl染色可见损伤侧海马CA2、CA3区锥体细胞层细胞消失或紊乱。损伤区周围皮质凋亡细胞伤后3d达到高峰；损伤侧海马凋亡细胞伤后5d达到高峰；损伤侧隔区凋亡细胞7d达到高峰。正常侧上述脑区各时相点均未见到凋亡细胞。损伤区周围皮质、损伤侧海马和隔区iNOS阳性细胞数量明显增加。损伤侧隔区ChAT阳性神经元也明显减少。结论：大鼠创伤性脑损伤后损伤区周围皮质和损伤侧海马、隔区细胞凋亡数量的变化与伤后时程有关。伤后细胞iNOS表达增加是导致细胞凋亡的因素。     

Race as a moderator of parent and family outcomes following pediatric traumatic brain injury

OBJECTIVE: To use data from a prospective, longitudinal study to determine whether race moderates parent and family outcomes during the first year following pediatric traumatic brain injuries (TBI). METHOD: Participants included 73 white and 18 black children with moderate to severe TBI and their families, and 32 white and 23 black children with orthopedic injuries only (OI) and their families. Assessments of parent and family functioning occurred shortly after injury (baseline) and at 6- and 12-month follow-ups. RESULTS: Race was a significant moderator of group differences in parental psychological distress and perceived family burden, by and large independent of socioeconomic status. The negative consequences of TBI were relatively less pronounced for parents of black children than for parents of white children at baseline, but became more pronounced at the two follow-ups. Black and white parents differed in preferred coping strategies, which may partially account for their different reactions to their children's injuries. CONCLUSIONS: The sociocultural factors associated with race may moderate the effects of pediatric TBI and OI on parents and families.     

Assessing and treating veterans with traumatic brain injury

Conflicts in Iraq and Afghanistan have resulted in greater proportions of service members with traumatic brain injury than in prior conflicts. These brain injuries range from the mild (concussion) to severe, and have enormous implications for clinical practice with these soldiers. The highly stressful and dangerous context in which these injuries are sustained set them apart in significant ways from brain injuries seen in civilian settings. The associated emotional toll of the environment and comorbid injuries, often resulting from blast exposure, complicates the clinical picture. In this article, the authors describe the complex presentations in this population of traumatically brain injured combat veterans and illustrate with case vignettes.     

MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury

We treated traumatic brain injury (TBI) with human bone marrow stromal cells (hMSCs) and evaluated the effect of treatment on white matter reorganization using MRI. We subjected male Wistar rats (n = 17) to controlled cortical impact and either withheld treatment (controls; n = 9) or inserted collagen scaffolds containing hMSCs (n = 8). Six weeks later, the rats were sacrificed and MRI revealed selective migration of grafted neural progenitor cells towards the white matter reorganized boundary of the TBI‐induced lesion. Histology confirmed that the white matter had been reorganized, associated with increased fractional anisotropy (FA; p < 0.01) in the recovery regions relative to the injured core region in both treated and control groups. Treatment with hMSCs increased FA in the recovery regions, lowered T₂ in the core region, decreased lesion volume and improved functional recovery relative to untreated controls. Immunoreactive staining showed axonal projections emanating from neurons and extruding from the corpus callosum into the ipsilateral cortex at the boundary of the lesion. Fiber tracking (FT) maps derived from diffusion tensor imaging confirmed the immunohistological data and provided information on axonal rewiring. The apparent kurtosis coefficient (AKC) detected additional axonal remodeling regions with crossing axons, confirmed by immunohistological staining, compared with FA. Our data demonstrate that AKC, FA, FT and T₂ can be used to evaluate treatment‐induced white matter recovery, which may facilitate restorative therapy in patients with TBI. Copyright © 2011 John Wiley & Sons, Ltd.     

马来酸桂哌齐特对大鼠颅脑损伤作用效果的实验研究

目的脑损伤后脑血管自发调节功能受损导致脑组织缺血缺氧是继发性脑损伤发病机理的重要环节。及时改善创伤后脑组织缺血缺氧状态对于创伤性脑损伤的预后极为重要。本研究对新型脑血管治疗药物克林澳(马来酸桂哌齐特注射液)在创伤性脑损伤中的神经保护作用进行探讨。方法雄性Sprague-Daw-ley大鼠50只,随机分三组:假手术组(n=20),中度液压脑损伤组(1.8~2.2atm)(n=20)(生理盐水3.0mg/kg静脉注射,30min and 24h post-injury),药物组:(克林澳3.0mg/kg静脉注射,30min and 24h post-injury)(n=10),于损伤后72h分别检测创伤侧及对侧皮层、海马及丘脑病理损伤。应用水迷宫实验对大鼠神经功能进行评价。结果脑损伤后皮层,海马以及丘脑神经元大量损伤,早期应用克林澳显著减轻创伤后神经元损伤。皮层、海马及丘脑分别减轻51%、35%、26%(P<0.05)。水迷宫实验平均上台时间及上台前游动总距离较对照组显著减少(P<0.05)。结论脑损伤后早期应用克林澳能显著减轻神经组织的病理损害,并改善神经功能。     

Apolipoprotein E genotype and oxidative stress response to traumatic brain injury

Traumatic Brain Injury (TBI) is known to result in oxidative stress, and as variation at the Apolipoprotein E (APOE) gene has been shown to influence outcome following TBI, but through as yet unclear mechanisms, we used transgenic APOE mouse models to examine the relationship between APOE genotype and oxidative stress following TBI. We administered a controlled cortical impact (CCI) injury or sham injury to transgenic mice expressing either human APOE3 or APOE4 on a murine APOE-deficient background. RNA was prepared from the ipsilateral hippocampi and cortices retrieved at 24 h and 1 month post-TBI. Microarray analysis was performed on unpooled samples from three mice per group to determine the genomic response to TBI and to specifically investigate the response of genes involved in oxidative stress mechanisms. Our data demonstrated TBI-induced expression of many more anti-oxidant related genes in the APOE3 mice, suggesting a potential anti-oxidative role for ApoE3 compared to ApoE4. However, in an additional cohort of mice we isolated the ipsilateral hippocampi, cortices, and cerebella at 1 month after TBI or sham injury for immunohistochemical analysis of markers of oxidative stress: the formation and presence of carbonyls (indication of general oxidative modification), 3-nitrotyrosine (3NT; specific to protein modification), or 4-hydroxyl-2-nonenal (HNE; specific to lipid peroxidation). Although we observed significant increases in all three markers of oxidative stress in response to injury, and genotype was a significant factor for carbonyl and 3NT, we found no significant interaction between genotype and injury. This may be due to the overwhelming effect of injury compared to genotype in our ANOVA, but nonetheless suggests that an influence on oxidative stress response is not the primary mechanism behind the APOE-genotype dependent effects on outcome following TBI.     

神经干细胞治疗脑创伤的研究进展

内源性神经干细胞通过迁移,激活的方式分化为神经元及胶质细胞,并改善神经功能,但创伤导致的复杂的微环境使内源性神经干细胞的增殖和分化受到限制。外源性神经干细胞可在宿主内存活并通过旁分泌功能改善局部微环境,促进内源性神经干细胞的增殖和分化,恢复神经元之间的连接功能,从而促进神经组织再生和功能修复。     

创伤性脑损伤后大鼠皮质AQP4表达的变化

目的 观察创伤性脑损伤后大鼠皮质水通道蛋白4(aquaporin4,AQP4)表达的变化.方法 采用Feency法建立脑损伤大鼠模型,取成年健康雄性wistar大鼠60只,随机分为6组,So、S1、S4、S1W、S2W及正常对照组.采用免疫组化和免疫印迹方法进行各组AQP4表达变化的观察及检测,进行图像分析和统计学处理...     

颅脑外伤后并发低钠血症的危险因素分析

目的探讨颅脑外伤患者并发低钠血症的发生机制及危险因素,以期为其早期预测及预防提供参考。方法回顾性分析2016年6月至2019年6月我院收治的185例中型和重型颅脑外伤患者的临床资料,包括导致低钠血症的不同病因、损伤类型、性别、格拉斯哥昏迷(GCS)评分、手术、脑水肿、颅底骨折和穿透性性损伤等;采用单因素χ^2检验和多因素Logistic回归分析探究颅脑外伤后并发低钠血症的危险因素。结果所有患者中,80例出现低钠血症,其中钠盐摄入不足、利尿剂过量使用47例,抗利尿激素分泌失调综合征19例,脑性耗盐综合征14例。低钠血症更多发生在脑挫裂伤、蛛网膜下腔出血和弥漫性轴索损伤患者中,差异具有统计学意义(P<0.05)。单因素χ^2检验结果显示,GCS评分(P=0.000)、脑水肿(P=0.000)、颅底骨折(P=0.000)、穿透性损伤(P=0.001)是颅脑外伤后并发低钠血症的相关因素。多因素Logistic回归分析结果显示,GCS评分(P=0.006)、脑水肿(P=0.006)、颅底骨折(P=0.000)、穿透性损伤(P=0.015)是颅脑外伤后并发低钠血症的危险因素。结论脑挫裂伤、蛛网膜下腔出血、弥漫性轴索损伤、GCS评分≤8分、脑水肿、颅底骨折和穿透性损伤的颅脑外伤患者更易发生低钠血症,应早期关注患者血清钠水平,明确病因及时纠正,防止病情恶化。     

重组人促红细胞生成素改善小鼠创伤性脑损伤神经功能

目的探讨重组人促红细胞生成素(rhEPO)对小鼠创伤性脑损伤(TBI)血管生成及神经功能恢复的影响。方法将小鼠随机分为假手术组(sham组)、模型组(TBI组,控制性皮质撞击制作重型TBI模型)和治疗组[EPO组,损伤后连续7 d腹腔注射5000 IU/(kg·d)rhEPO],每组小鼠15只。伤后3、7和14 d进行神经功能缺损评分(mNSS),14 d以Western blot及免疫荧光法检测脑损伤灶周边区域eNOS、VEGF和CD31蛋白表达,并通过CD31+细胞进行微血管密度计数(MVD);21 d以苏木精-伊红(HE)染色大脑切片并检测损伤灶体积。结果伤后3、7及14 d,TBI组较sham组mNSS明显上升(P<0.001),伤后7及14 d EPO组mNSS低于TBI组(P<0.05)。伤后14 d,损伤灶周边区eNOS、VEGF和CD31蛋白的表达,TBI组较sham组升高(P<0.05),EPO组较TBI组升高(P<0.05);TBI组的MVD显著低于sham组(P<0.001),EPO组的MVD显著高于TBI组(P<0.001)。伤后21 d EPO组较TBI组创伤体积减小(P<0.05)。结论rhEPO促进小鼠TBI血管生成,改善颅脑损伤后神经功能。     

Apolipoprotein E-genotype dependent hippocampal and cortical responses to traumatic brain injury

The different alleles of the apolipoprotein E gene (APOE-gene, ApoE-protein) have been reported to influence recovery after traumatic brain injury (TBI) in both human patients and animal models, with the e4 allele typically conferring poorer prognosis for recovery. How the E4 allele, and consequently the ApoE4 isoform, affects recovery is unknown, but proposed mechanisms include neurogenesis, inflammatory response and amyloid processing or metabolism. Using the controlled cortical impact (CCI) model of brain injury and microarray technology we have characterized the genomic response to injury in the brains of APOE2, APOE3 and APOE4 transgenic mice and identified quantitatively and qualitatively significantly different profiles of gene expression in both the hippocampus and the cortex of the APOE3 mice compared to APOE4. The observed gene regulation predicts functional consequences including effects on inflammatory processes, cell growth and proliferation, and cellular signaling, and may suggest that the poor recovery post-TBI in APOE4 animals and human patients is less likely to result from a specific activation of neurodegenerative mechanisms than a loss of reparative capability.     

大鼠脑外伤时嘌呤受体P2X4受体的表达

目的：观察大鼠脑外伤后嘌呤受体亚型P2X4的表达水平。方法：免疫组织化学和半定量RT—PCR。结果：脑外伤后P2X4受体表达水平迅速升高，并在损伤后较长的时间内维持高的表达水平；脑外伤早期，损伤区P2X4免疫反应阳性细胞主要是圆形细胞，中后期主要以具有突起的细胞为主。结论：脑外伤早期，损伤区P2X4受体免疫反应阳性细胞主要为小胶质细胞，中后期可能星形胶质细胞为多；由此推测P2X4参与脑外伤时大脑生理或病理生理功能的调节。     

Clinical predictors of prognosis in patients with traumatic brain injury combined with extracranial trauma

Objective: The purpose of this study was to investigate whether routine blood tests on admission and clinical characteristics can predict prognosis in patients with traumatic brain injury (TBI) combined with extracranial trauma.Methods: Clinical data of 182 patients with TBI combined with extracranial trauma from April 2018 to December 2019 were retrospectively collected and analyzed. Based on GOSE score one month after discharge, the patients were divided into a favorable group (GOSE 1-4) and unfavorable group (GOSE 5-8). Routine blood tests on admission and clinical characteristics were recorded.Results: Overall, there were 48 (26.4%) patients with unfavorable outcome and 134 (73.6%) patients with favorable outcome. Based on multivariate analysis, independent risk factors associated with unfavorable outcome were age (odds ratio [OR], 1.070; 95% confidence interval [CI], 1.018-1.124; p<0.01), admission Glasgow Coma Scale (GCS) score (OR, 0.807; 95% CI, 0.675-0.965; p<0.05), heart rate (OR, 1.035; 95% CI, 1.004-1.067; p<0.05), platelets count (OR, 0.982; 95% CI, 0.967-0.997; p<0.05), and tracheotomy (OR, 15.201; 95% CI, 4.121-56.078; p<0.001). Areas under the curve (AUC) of age, admission GCS, heart rate, tracheotomy, and platelets count were 0.678 (95% CI, 0.584-0.771), 0.799 (95% CI, 0.723-0.875), 0.652 (95% CI, 0.553-0.751), 0.776 (95% CI, 0.692-0.859), and 0.688 (95% CI, 0.606-0.770), respectively.Conclusions: Age, admission GCS score, heart rate, tracheotomy, and platelets count can be recognized as independent predictors of clinical prognosis in patients with severe TBI combined with extracranial trauma.     

The evolution of traumatic brain injury in a rat focal contusion model

Serial MRI facilitates the in vivo analysis of the intra‐ and intersubject evolution of traumatic brain injury lesions. Despite the availability of MRI, the natural history of experimental focal contusion lesions in the controlled cortical impact (CCI) rat model has not been well described. We performed CCI on rats and MRI during the acute to chronic stages of cerebral injury to investigate the time course of changes in the brain. Female Wistar rats underwent CCI of their left motor cortex with a flat impact tip driven by an electromagnetic piston. In vivo MRI was performed at 7 T serially over 6 weeks post‐CCI. The appearances of CCI‐induced lesions and lesion‐associated cortical volumes were variable on MRI, with the percentage change in cortical volume of the CCI ipsilateral side relative to the contralateral side ranging from 18% within 2 h of injury on day 0 to a peak of 35% on day 1, and a trough of –28% by week 5/6, with an average standard deviation of ±14% at any given time point. In contrast, the percentage change in cortical volume of the ipsilateral side relative to the contralateral side in control rats was not significant (1 ± 2%). Hemorrhagic conversion within and surrounding the CCI lesion occurred between days 2 and 9 in 45% of rats, with no hemorrhage noted on the initial scan. Furthermore, hemorrhage and hemosiderin within the lesion were positive for Prussian blue and highly autofluorescent on histological examination. Although some variation in injuries may be technique related, the divergence of similar lesions between initial and final scans demonstrates the inherent biological variability of the CCI rat model. Published 2012. This article is a US Government work and is in the public domain in the USA.     

综合性护理在重症颅脑损伤患者术后护理中的应用

目的：探讨综合性护理在重症颅脑损伤患者术后护理中的应用价值。方法：将60例重症颅脑损伤的患者用随机数字表法分为观察组和对照组,对照组围手术期采用常规护理,观察组术后采用综合护理,比较两组患者的并发症、生命体征、住院时间以及护理满意度。结果：观察组护理后的SOFA、APACHEII评分低于对照组,GCS评分高于对照组,有统计学意义(P<0.05)。观察组的并发症少于对照组,焦虑评分低于对照组,入住ICU、住院时间短于对照组,护理满意度高于对照组,有统计学意义(P<0.05)。结论：综合性护理能减少重症颅脑手术患者术后并发症,改善预后。