铁代谢在创伤性颅脑损伤中的研究进展

创伤性颅脑损伤(traumatic brain injury,TBI)是一类由多种因素导致的颅脑损伤性疾病,可引起一系列复杂的病理生理过程.缺乏早期干预靶点是TBI预后不良的重要因素.另外,TBI不良预后与损伤脑组织铁代谢紊乱密切相关,铁代谢调节干预,尤其是铁螯合剂,在TBI中显示出巨大治疗潜力.本文将对铁代谢与TBI...     

颅脑损伤程度对大鼠脑血流及氧代谢的影响

目的 对颅脑损伤影响脑血流及氧代谢进行前瞻性研究。方法 30只Wistar大白鼠分成3组：颅脑损伤1组（TBI1）、2组（TBI2）及3组（TBI3）各10只,分别为轻、中、重型颅脑损伤。用脑阻抗（REG）测定脑血流量,颈内静脉血氧饱和度（SjVO2)反映全脑氧代谢情况。结果 TBI、TBI2及TBI3组影响脑血流和氧代谢程度依次为TBI3＞TBI2＞TBI1,健侧脑组织含水量各组无明显差异,伤侧脑组织含水量TBI3组最多,其次为TBI2,明显高于TBI1组（P＜0．01）。结论 颅脑损伤后脑血流和氧代谢变化取决于损伤程度,脑血流和氧代谢各参数的监测对正确认识脑组织病理生理变化,指导临床治疗,判断预后有重要价值。     

CXCL12与创伤性颅脑损伤后神经细胞凋亡的相关性

创伤性颅脑损伤（TBI）后的神经细胞凋亡是继发性TBI中最严重的病理生理变化，是临床上致残、致死率高的重要原因。有效控制神经细胞凋亡是治疗TBI的关键，直接关系到TBI患者的预后。CXCL12是一类具有趋化活性的细胞因子，在中枢神经系统有广泛的表达，在神经保护、神经功能调节、神经细胞发生和神经炎症反应中起着关键作用。随着研究的不断深入，发现CXCL12与TBI后神经细胞凋亡有着密切的联系。本文就CXCL12与TBI后神经细胞凋亡关系的研究进展展开综述。     

脑创伤患者睡眠障碍研究进展

颅脑创伤(Traumatic Brain Injury,TBI)后睡眠障碍发病率高,超过一半的TBI患者存在失眠,大约46%的TBI患者存在睡眠中呼吸暂停、睡眠过度、嗜睡和周期性肢体运动等。下丘脑损伤导致的神经递质减少可能参与了过度睡眠的病理生理。依据睡眠障碍治疗指南可以有效治疗部分患者。促醒药物和中枢神经系统刺激疗法对嗜睡、睡眠时间延长和白天过度睡眠的疗效需要进一步研究。加强对睡眠时间延长和昼夜节律紊乱病理生理的多中心研究,对有效治疗相关疾病具有重要意义。     

内皮祖细胞分泌的外泌体在颅脑损伤中作用的研究进展

正颅脑损伤(traumatic brain injury,TBI)具有较高的发病率和病死率,是青壮年最常见的死亡和残疾原因。全球每年约有5 000万例TBI,年经济损失约4 000亿美元,占世界生产总值的0.5%[1]。TBI后神经组织的损伤和修复是一个复杂的病理生理过程,多种细胞参与其中,其中外泌体介导的细胞间信号传导和相互调控具有重要意义。内皮祖细胞(endothelial progenitor cells,EPCs)来源于骨髓和外周血管壁,是血管内皮细胞(endothelial cells,ECs)的前体细胞[2]。     

热量限制在颅脑创伤中的应用进展

颅脑创伤(Traumatic Brain Injury,TBI)是世界范围内年轻人和成年人致死、致残的最重要的原因之一,每年 TBI 罹患人数超过1000万[1].TBI 后脑组织的细胞死亡一部分由直接机械损伤(原发性)引起,但是更多是由损伤后一系列生化改变(继发性)引起的.这些继发性损伤包括：细胞因子释放引起的炎性反应,谷氨酸毒性,突触功能障碍,活性氧、活性氧损伤,神经元功能障碍等,这些可进一步引起线粒体功能障碍,也可使细胞死亡信号级联效应放大,最终导致神经元的死亡[2－6].对这些病理生理机制进行深入的研究可为临床的治疗提供理论依据。     

高迁移率族蛋白B1在颅脑损伤后炎症反应中作用

<正>颅脑损伤(traumatic brain injury,TBI)是一个全球性问题,涉及病人多、范围广。TBI病理过程包括原发性损伤和继发性损伤,后者是直接损伤造成的一系列细胞及生化级联反应,是TBI致死的主要原因~([1-3]),炎症反应是继发性脑损伤过程中最关键的病理过程~([4,5])。高迁移率族蛋白B1(high mobility group protein B1,HMGB1)释放在TBI后炎症反应中起着重要作用,继发性脑损伤中H1MGB1的作用逐渐引起重视。本文对近年来TBI中HMGB1的研究进展进     

靶向抑制frizzled-2对脑损伤后wnt5a/Ca~(2+)介导的神经细胞钙超载的抑制性研究（英文）

目的探讨Wnt5a/Frizzled-2信号在创伤性颅脑损伤(TBI)后神经细胞钙超载过程中的作用。方法体内实验:成年Sprague-Dawley大鼠(96只),随机分为正常组A(32只),单纯损伤组B(32只)和RNAi抑制组C(32只)。B组和C组Fenny式法制作中型颅脑损伤模型。其中C组模型建立前48 h采用立体定向海马区注射RNAi以抑制Frizzled-2的表达。伤后24 h处死大鼠,取伤侧海马组织,用western blotting方法检测其中Frizzled-2和Wnt5a含量,用免疫荧光染色和激光共聚焦显微镜检测其中钙离子浓度。单因素方差分析比较各组间的差别。结果 A组大鼠海马组织细胞中稳定表达着Wnt5a/Frizzled-2信号。TBI后,与A组相比,B组海马组织中的Wnt5a和Frizzled-2的表达分别升高了2倍和5倍(P0.01),海马细胞中钙离子的含量显著增高(P0.01)。与B组相比,随着Frizzled-2的抑制,C组海马细胞中的Wnt5a和Frizzled-2的表达分别降低1倍、3.5倍(P0.01),同时细胞中的钙离子含量显著降低1.5倍,接近A组(P0.01)。结论在生理和病理条件下,Wnt5a/Frizzled-2信号在调节神经细胞中的钙离子浓度变化中起到重要的作用,同时我们的研究提示该信号的相关重要组成因子Wnt5a,Fzd2和P-CamKII以及针对Frizzled-2设计的特异性RNAi可以作为日后TBI研究和治疗的相关靶点。     

靶向铁死亡药物治疗创伤性颅脑损伤的研究进展

创伤性脑损伤（TBI）是由外力撞击引起的一种机械损伤性疾病,包括原发性损伤和继发性损伤。抑制继发性损伤的细胞死亡药物疗法对改善TBI患者的预后和生活质量具有重要意义。铁死亡是一种铁依赖的脂质过氧化诱发的细胞程序性死亡,参与多种急性和慢性神经系统疾病的生理病理调控。研究发现,铁死亡参与了TBI继发性损伤的神经元死亡机制,并与TBI后的长期预后相关。该文总结了靶向铁死亡治疗TBI患者的潜在药物,通过对TBI采取针对性和精准化策略干预,最终防止TBI继发性损伤后的神经细胞铁死亡,达到保护神经组织,减轻患者伤残率和病死率的目的。     

氢质子磁共振波谱成像技术在创伤性脑损伤后认知障碍中的应用

创伤性脑损伤(TBI)可引起一系列复杂的病理生理过程变化,这些变化包括脑内物质代谢异常,导致机体出现包括头痛、认知、运动和情感障碍等在内的长、短期症状,而认知障碍是阻碍TBI患者日常生活质量恢复和延缓其回归社会的重要因素。氢质子磁共振波谱成像技术(1H-MRS)可对急、慢性脑部损伤患者的脑组织代谢进行非侵入性检测,具有辅助诊断和预测长期功能预后的价值。该文将近年来1H-MRS在TBI后认知障碍中的应用进行总结和展望。[国际神经病学神经外科学杂志, 2021, 48(2):197-201]     

Sleep: big brain meets little brain

2001 Harcourt Publishers Ltd     

Measuring brain temperature while maintaining brain normothermia in patients with severe traumatic brain injury

The aim of this study was to evaluate the relationship between superficial temporal artery temperature (Tt), rectal temperature (Tr) and intracranial temperature (ICT) when attempting to keep the brain in a normothermic condition in patients with severe traumatic brain injury (TBI). We also compared the incidence of temperature gradient reversal in patients who survived (survivors) and patients who did not (non-survivors) and the difference in temperature gradient reversal between survivors and non-survivors. Tr is normally lower than and ICT and temperature gradient reversal, when Tr exceeds ICT, has been demonstrated to be an early sign of brain death. A total of 28 patients with severe TBI were enrolled retrospectively in our study between November 2008 and February 2010. Each patient’s Tt, Tr and ICT was recorded every hour for 4 days. Our results show that the frequency of brain hyperthermia in our participants (ICT > 38 °C) was 17.7%. Using a paired t-test and Bland-Altman plots, it was shown that a significant temperature difference existed between Tt, Tr and ICT (p < 0.001). The use of Spearman’s correlation method revealed that Tt, Tr and ICT were positively correlated (p < 0.001). Brain death occurred in five patients at a mean of 9.6 hours (range: 8-12 hours) after a temperature gradient reversal between Tt, Tr and ICT. Fisher’s exact test showed that there was a significant difference in the incidence of temperature gradient reversal between Tt, Tr and ICT in survivors and non-survivors (p < 0.001). We conclude that a significant temperature difference exists between Tt, Tr and ICT when maintaining brain normothermia. The daily practice of non-invasive Tt measurement may cause doctors to underestimate ICT; reversal of the ICT and Tt and/or Tr temperatures could be an early marker of a poor prognosis for patients with severe TBI.     

Repeat traumatic brain injury in the developing brain

The Center for Disease Control estimates that there are 1.7 million brain injuries in the US each year with 51% of these injuries occurring during periods of cerebral development. Among this population there is a growing population of individuals with repeat traumatic brain injury (RTBI). While the exact incidence is unknown, estimates range from 5.6 to 36% of the TBI population. This review summarizes the clinical problems/challenges and experimental research models that currently exist. It is intended to reveal the critical areas that need to be addressed so that age-relevant clinical management guidelines can be established to protect this population.     

梗死灶切除治疗重型颅脑外伤合并大面积脑梗死

目的探讨重型颅脑外伤合并大面积脑梗死的最佳外科处理方式.方法对53例重型颅脑外伤病人行开颅血肿、挫伤脑组织清除术加去骨瓣减压术,其中31例未行梗死灶切除(第1组),22例行梗死灶切除(第2组).术后1个月、12个月评价两组的GOS,并行χ2检验.结果术后第1组死亡7例,植物生存5例,重残8例,轻残11例;第2组死亡1例,植物生存2例,重残9例,轻残10例.两组不良结果率(死亡 植物状态)有显著性差异,P＜0.05.结论对重型颅脑外伤合并大面积脑梗死的病人行挫伤脑组织和血肿加梗死灶切除,对降低病死率、提高有效生存率有明显作用.     

Clinical cerebral microdialysis: brain metabolism and brain tissue oxygenation after acute brain injury.

While continuous monitoring of brain tissue oxygenation (P(ti)O2) is known as a practicable, safe and reliable monitoring technology supplementing traditional ICP-CPP-monitoring, the impact of cerebral microdialysis, now available bedside, is not proven extensively. Therefore our studies focused on the practicability, complications and clinical impact of microdialysis during long term monitoring after acute brain injury, especially the analysis of the correlation between changes of local brain oxygenation and metabolism. Advanced neuromonitoring including ICP-CPP-p(ti)O2 was performed in 20 patients suffering from acute brain injury. Analysis of the extracellular fluid metabolites (glucose, lactate, pyruvate, glutamate) were performed bedside hourly. No catheter associated complications, like infection and bleeding, occurred. However, longterm monitoring was limited in 5 out of 20 patients caused by obliteration of the microdialysis catheter after 3-4 days. In the individual patients partly a correlation between increased lactate levels as well as lactate pyruvate ratios and hypoxic brain tissue oxygenation could be found. Analysing the data sets of all patients only a low correlation was detected indicating physiological and increased lactate and lactate/pyruvate ratio during sufficient brain oxygenation. Additionally, concentrations of excitatory amino acid glutamate were found in normal and elevated range during periods of hypoxic oxygenation (P(ti)O2 < 10 mmHg) and intracranial hypertension. Our data strongly suggest partly evidence of correlation between hypoxic oxygenation and metabolic disturbances after brain injury. On the other hand brain metabolism is altered without changes of cerebral oxygenation. Further studies are indicated to improve our pathophysiological knowledge before microdialysis is routinely useful in neurointensive care.