基质金属蛋白酶在脑创伤中的研究进展

脑创伤是目前严重危害人类健康的主要疾病之一，具有较高的致残率和死亡率。而继发性脑损伤是影响脑创伤发展和预后的重要因素之一，适当的治疗可以减轻或避免某些继发性损伤的病理变化，提高患者的疗效，改善预后。近年来，随着对基质金属蛋白基质系（matrix metalloproteinases，MMPs）的不断深入研究，金属蛋白酶系在继发性脑损伤中的作用日益受到人们的重视。本文就基质金属蛋白酶系在脑创伤方面的研究概述如下。[第一段]     

Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases

The role of intracellular proteases (e.g., calpains and caspases) in the pathophysiology of neuronal cell death has been extensively investigated. More recently, accumulating data have suggested that extracellular proteolysis also plays a critical role. The two major systems that modify the extracellular matrix in brain are the plasminogen activator (PA) and matrix metalloproteinase (MMP) axes. This Mini-Review delineates major pathways of PA and MMP action after stroke, brain trauma, and chronic inflammation. Deleterious effects include the disruption of blood-brain barrier integrity, amplification of inflammatory infiltrates, demyelination, and possibly interruption of cell-cell and cell-matrix interactions that may trigger cell death. In contrast, PA-MMP actions may contribute to extracellular proteolysis that mediates parenchymal and angiogenic recovery after brain injury. As the mechanisms of deleterious vs. potentially beneficial PA and MMP actions become better defined, it is hoped that new therapeutic targets will emerge for ameliorating the sequelae of brain injury and inflammation.     

The potential role of mitochondria in pediatric traumatic brain injury

Mitochondria play a central role in cerebral energy metabolism, intracellular calcium homeostasis and reactive oxygen species generation and detoxification. Following traumatic brain injury (TBI), the degree of mitochondrial injury or dysfunction can be an important determinant of cell survival or death. Literature would suggest that brain mitochondria from the developing brain are very different from those from mature animals. Therefore, aspects of developmental differences in the mitochondrial response to TBI can make the immature brain more vulnerable to traumatic injury. This review will focus on four main areas of secondary injury after pediatric TBI, including excitotoxicity, oxidative stress, alterations in energy metabolism and cell death pathways. Specifically, we will describe what is known about developmental differences in mitochondrial function in these areas, in both the normal, physiologic state and the pathologic state after pediatric TBI. The ability to identify and target aspects of mitochondrial dysfunction could lead to novel neuroprotective therapies for infants and children after severe TBI.     

The role of the complement system in traumatic brain injury

A traumatic impact to the brain induces an intracranial inflammatory response, which consequently leads to the development of brain edema and delayed neuronal death. Evidence from experimental, clinical, and in vitro studies highlight an important role for the complement system in contributing to inflammation within the injured brain. The present review summarizes the current understanding of the mechanisms of complement-mediated secondary brain injury after head trauma.     

The role of depression in verbal memory following traumatic brain injury

The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.     

NF-κB在继发性脑外伤中的作用

近年来,国内外研究结果表明,脑外伤所激发的局部炎症反应在伤情的发展和预后方面起着重要的作用.局部神经组织的变性坏死、脑血流自身调节功能的改变、血脑屏障通透性改变及血管性和细胞毒性脑水肿的发生、损伤区神经组织生化代谢的紊乱和神经递质的变化以及脑组织的修复等都与炎症反应有着密切的联系.     

Cortical laminar necrosis in an infant with severe traumatic brain injury

Cortical laminar necrosis appears as hyperinense lesions with a laminar pattern on T1 weighted magnetic resonance (MR) imaging, without signs of hemorrhage or calcification on T2 weighted MR imaging or computed tomography. It has been reported to be associated with hypoxia, metabolic disturbances, drugs, and infections. We present a 12 month-old male infant who suffered diffuse brain injuries following car accident and showed laminar necrosis of cortex.     

The current role of decompressive craniectomy for severe traumatic brain injury

There is little doubt that decompressive craniectomy can reduce mortality however, the results of a recent study has provided more evidence to inform the debate regarding clinical and ethical concerns that it merely converts death into survival with severe disability or in a vegetative state. The recently published RESCUEicp trial compared last-tier secondary decompressive craniectomy with continued medical management for refractory intracranial hypertension after severe traumatic brain injury. Patients were randomly assigned to decompressive craniectomy with medical therapy or to receive continued medical therapy with the option of adding barbiturates. The results of the study support the findings of the stroke studies in that the reduction in mortality was almost directly translatable into survival with either severe disability or in a vegetative state. The question remains as to whether there is a subset of patients who obtain benefit from surgical decompression and it is in this regard that the use of observational cohort studies and sophisticated outcome prediction models may be of use. Comparing the percentage prediction with the observed long outcome provides an objective assessment of the most likely outcome can be obtained for patients thought to require surgical intervention. Whilst there will always be limitations when using this type of data they may help prompt appropriate patient-centred discussions regarding realistic outcome expectations. A broader debate is also needed regarding use of a medical intervention that may leave a person in a condition that they may feel to be unacceptable and also places a considerable burden on society.     

基质金属蛋白酶/金属蛋白酶组织抑制因子在大鼠创伤性深静脉血栓形成中的表达及作用

背景：创伤性深静脉血栓形成机制复杂，大量研究主要集中在临床观察和流行病学层面，其分子机制研究一直没有新的突破。 目的：应用基因芯片技术研究创伤性深静脉血栓形成过程中基质金属蛋白酶的表达变化规律，探讨其在创伤性深静脉血栓形成中的作用。 方法：SPF级8~12周龄SD大鼠150只，体质量250~300 g，随机分为正常对照组10只和模型组140只。模型组140只采用直接钳夹股静脉+双后肢石膏固定方式，建立大鼠创伤性深静脉血栓动物模型。又分为7组亚组，创伤即刻组(0.5 h)、血栓形成初始期组(2.5 h)、高峰期血栓形成组(25 h)、高峰期血栓不形成组(25 h)、血栓消退组(72 h)、血栓不消退组(72 h)和创伤后持续无血栓组(168 h)，每组10只。在相应时相点无创切取股静脉血管组织，随后抽取总RNA，采用Genechip Rat Genome 430 2.0芯片对股静脉血管组织进行基因表达检测。观察创伤性深静脉血栓形成与不形成和消退与不消退的发生率；运用基因芯片数据分析方法分析基质金属蛋白酶和金属蛋白酶组织抑制因子在各时相点的表达。 结果与结论：模型组死亡3只，147只大鼠进入结果分析。造模后25 h血栓形成率约为50.5%，血栓不形成率约为49.5%；168 h，有血栓的大鼠中大概有56.7%发生消退，43.3%的血栓持续存在不消退。基质金属蛋白酶和金属蛋白酶组织抑制因子等均呈不同程度差异表达。血栓不消退状态时，基质金属蛋白酶仍呈高表达，金属蛋白酶组织抑制因子表达在血栓形成过程中处于下调状态，在消退过程呈明显抑制状态。在创伤性深静脉血栓形成与消退演化过程中，创伤后基质金属蛋白酶与创伤性深静脉血栓之间存在密切的关系，基质金属蛋白酶/ 金属蛋白酶组织抑制因子可能是影响血栓生物学状态的重要因素之一。     

婴幼儿颅脑损伤后大面积脑缺血的临床特征及治疗

目的总结分析婴幼儿颅脑损伤后大面积脑缺血的临床特点。方法回顾性研究41例婴幼儿颅脑损伤后大面积脑缺血患者的致伤原因、损伤类型、临床表现，以及救治方法和预后状况。结果41例患儿中坠落伤24例，占58．5％；新生儿产伤10例，占24．4％，二者合计占82．9％。30例（73．2％）患儿伤后症状进行性加重，11例（26．8％）患儿病情稳定后又分别出现新的症状，复查头颅CT发现大面积脑缺血。而伤后1d内出现大面积缺血6例，1-3d出现的23例，3d至1W以上出现12例。经颅多普勒（TCD）检测11例大脑中动脉血流峰速（Vm）120cm／s〈Vm〈140cm/s，5例90cm／s〈Vm〈120cm／s，5例Vm〉140cm／s，2例Vm〈30cm／s。手术治疗34例，主要行颅内血肿清除术、减压术等。41例患儿均接受尼莫同、罂粟碱、丹参、低分子右旋糖酐等不同药物组合治疗。部分病例还给予静脉滴注尿激酶。格拉斯哥预后评级（GOS）：恢复良好22例（53．7％）；中残8例（19．5％）；重残5例（12．2％）；植物生存1例（2．44％）；死亡5例，死亡率12．2％。结论婴幼儿颅脑损伤后大面积脑缺血的病例以坠落伤和新生儿产伤较多见，脑缺血的发生与硬膜下血肿、脑挫裂伤所致的脑血管痉挛有紧密的关系，大面积脑缺血的危害性大，致残、致死率高，早期的扩张血管和改善循环治疗，是预防和改善颅脑创伤后大面积脑缺血的最为有效的治疗方法。     

基质金属蛋白酶在脑胶质细胞瘤研究中的应用前景

在中枢神经系统肿瘤的治疗中,脑胶质细胞瘤侵袭性生长的特性是临床面临的重大挑战,它往往是造成患者肿瘤复发、预后欠佳或死亡的首要原因[1]。在未接受化学治疗的患者中,其平均生存期由17w(不接受任何治疗)至30w(接受手术治疗和放射治疗)不等。尽管化学治疗会带来多种副作用,但     

Understanding deficits in empathy after traumatic brain injury: The role of affective responsivity

People with traumatic brain injury (TBI) often find social situations challenging because they can no longer respond to the emotional state of the people they are with. Many also lack emotional empathy in their social interactions. But are these problems related? The present study addressed this question by examining psychophysiological indices of emotional responding, including facial electromyography (EMG) and skin conductance during exposure to happy and angry facial expressions, in addition to self-rated emotional empathy in 21 adults with severe TBI and 22 control participants. In comparison to control participants, those in the TBI group displayed a reduction in the ability to empathize emotionally, and showed reduced physiological responding to the emotional expression of anger. By contrast, the control group spontaneously mimicked the emotional expressions they were exposed to, regardless of affective valence, and also demonstrated higher skin conductance responsivity to angry faces. The data further suggested that a loss of emotional empathy plays a role in the emotional response deficits to angry facial expressions following TBI. The results have implications for understanding the impaired social functioning and poor quality of interpersonal relationships commonly seen as a consequence of TBI.     

The neuroendocrine effects of traumatic brain injury

Neuroendocrine dysfunction after traumatic brain injury (TBI) is under-diagnosed, under-treated, and may adversely affect the rate of recovery. Single or multiple pituitary-target hormone disruption occurs in up to two-thirds of persons with TBI, most commonly affecting the gonadal and growth hormone axes. The time course of decline in and recovery of pituitary function in relation to cognitive dysfunction and rehabilitation progress are not well described. This article reviews the clinical spectrum of neuroendocrine deficits after TBI and their underlying mechanisms. Future studies of the effects of hormonal replacement on recovery are recommended.     

Coagulopathy in traumatic brain injury

Abnormalities in blood coagulation, although quite common after traumatic brain injury (TBI), are of unknown significance. The authors review the clinical and pathophysiological features of this phenomenon and emphasize its origin in disseminated intravascular coagulation. This connection provides a possible explanation for much of the cerebral ischema that accompanies TBI, namely intravascular microthrombosis. The authors’ own research findings support this contention and suggest possible therapeutic avenues. A number of compelling studies demonstrate that DIC is a common and important consequence of TBI. In particular, posttraumatic coagulapathy appears to be linked to secondary cerebral injury. Although the extent of this process has yet to be elucidated fully, coagulation abnormalities are evident soon after trauma. This allows early identification of patients likely to suffer secondary complications and provides an opportunity to evaluate promising agents that may mitigate posttraumatic DIC and related pathologies in these patients. This is an area deserving of more intensive research.