Development of Prolonged Focal Cerebral Edema and Regional Cation Changes Following Experimental Brain Injury in the Rat

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.     

Cathepsin B mRNA and protein expression following contusion spinal cord injury in rats

We provide the first data that cathepsin B (Cath B), a lysosomal cysteine protease, is up-regulated following contusion-spinal cord injury (SCI). Following T12 laminectomy and moderate contusion, Cath B mRNA and protein expression profiles were examined from 2 to 168 h post-injury in rats using real-time PCR and immunoblots, respectively. Contusion injury significantly increased [mRNA]Cath B in the injury site and adjacent segments over sham injury levels. While the largest [mRNA]Cath B induction (20-fold over naive) was seen in the injury site, the caudal segment routinely yielded [mRNA]Cath B levels greater than 10-fold over naive. Interestingly, sham injury animals also experienced mRNA induction at several time points at the injury site and in segments rostral and caudal to the injury site. Contusion injury also significantly elevated levels of Cath B proenzyme protein (37 kDa) over sham injury in the injury site (48, 72 and 168 h post-injury). Furthermore, significant protein increases of single and double chain Cath B (both active forms) occurred at the injury site at 72 and 168 h post-injury. Similar significant increases in Cath B protein levels were seen in areas adjacent to the injury site. The induction of Cath B mRNA and protein expression following contusion injury is previously undescribed and suggests that Cath B may potentially be involved in the secondary injury cascade, perhaps for as long as 1 week post-injury.     

体外肝细胞损伤模型分子机制探讨

肝损伤是临床常见的危害人类健康的疾病,是各种原因引起肝脏疾病的共同的表现,也是各型肝病共同的病理基础。建立稳定可靠体外肝细胞损伤模型,对于肝损伤病理机制研究及有效防治肝损伤药物筛选提供了前提。针对肝细胞损伤分子机制不同,目前已成功建立基于免疫损伤、氧化损伤、脂肪损伤等体外肝细胞损伤模型,用于临床药物筛选及疗效作用机制研究,本文对目前常见体外肝细胞损伤模型及其发生的分子生物学机制进行探讨。     

Integrative biology of injury in animals

Mechanical injury is a prevalent challenge in the lives of animals with myriad potential consequences for organisms, including reduced fitness and death. Research on animal injury has focused on many aspects, including the frequency and severity of wounding in wild populations, the short- and long-term consequences of injury at different biological scales, and the variation in the response to injury within or among individuals, species, ontogenies, and environmental contexts. However, relevant research is scattered across diverse biological subdisciplines, and the study of the effects of injury has lacked synthesis and coherence. Furthermore, the depth of knowledge across injury biology is highly uneven in terms of scope and taxonomic coverage: much injury research is biomedical in focus, using mammalian model systems and investigating cellular and molecular processes, while research at organismal and higher scales, research that is explicitly comparative, and research on invertebrate and non-mammalian vertebrate species is less common and often less well integrated into the core body of knowledge about injury. The current state of injury research presents an opportunity to unify conceptually work focusing on a range of relevant questions, to synthesize progress to date, and to identify fruitful avenues for future research. The central aim of this review is to synthesize research concerning the broad range of effects of mechanical injury in animals. We organize reviewed work by four broad and loosely defined levels of biological organization: molecular and cellular effects, physiological and organismal effects, behavioural effects, and ecological and evolutionary effects of injury. Throughout, we highlight the diversity of injury consequences within and among taxonomic groups while emphasizing the gaps in taxonomic coverage, causal understanding, and biological endpoints considered. We additionally discuss the importance of integrating knowledge within and across biological levels, including how initial, localized responses to injury can lead to long-term consequences at the scale of the individual animal and beyond. We also suggest important avenues for future injury biology research, including distinguishing better between related yet distinct injury phenomena, expanding the subjects of injury research to include a greater variety of species, and testing how intrinsic and extrinsic conditions affect the scope and sensitivity of injury responses. It is our hope that this review will not only strengthen understanding of animal injury but will contribute to building a foundation for a more cohesive field of ‘injury biology’.     

大鼠侧位液压冲击脑损伤动物模型的病理生理学观察

目的：建立一种重复性好的大鼠分级侧位液压冲击脑损伤模型,为进一步研究外伤性脑损伤的分子机制提供物质基础。方法：雄性ＳＤ大鼠,随机分为正常对照组,手术对照组和损伤组损作组接冲击力大小分为轻（１００ｋＰａ）、中（２００ｋＰａ）、重（３００ｋＰａ）３个亚组。实验中由计算机记录冲击时脑承受的压力曲线并描记大鼠血压和心率变化。结果：脑承受的压力曲线与冲击气压呈直线正相关（ｒ＝０．９８５）,损伤组大鼠在冲击后     

Critical role of acrolein in secondary injury following ex vivo spinal cord trauma

The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein-Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.     

Method used to establish a large animal model of drug-induced acute kidney injury

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.     

Regional Levels of Lactate and Norepinephrine After Experimental Brain Injury

Abstract: The recently developed controlled cortical impact model of brain injury in rats may be an excellent tool by which to attempt to understand the neurochemical mechanisms mediating the pathophysiology of traumatic brain injury. In this study, rats were subjected to lateral controlled cortical impact brain injury of low grade severity; their brains were frozen in situ at various times after injury to measure regional levels of lactate, high energy phosphates, and norepinephrine. Tissue lactate concentration in the injury site left cortex was increased in injured animals by sixfold at 30 min and twofold at 2.5 h and 24 h after injury ( p < 0.05). At all postinjury times, lactate concentration was also increased in injured animals by about twofold in the cortex and hippocampus adjacent to the injury site ( p < 0.05). No significant changes occurred in the levels of ATP and phosphocreatine in most of the brain regions of injured animals. However, in the primary site of injury (left cortex), phosphocreatine concentration was decreased by 40% in injured animals at 30 min after injury ( p < 0.05). The norepinephrine concentration was decreased in the injury site left cortex of injured animals by 38% at 30 min, 29% at 2.5 h, and 30% at 24 h after injury ( p < 0.05). The level of norepinephrine was also reduced by ∼20% in the cortex adjacent to the injury site in injured animals. The present results suggest that controlled cortical impact brain injury produces disorder in the neuronal oxidative and norepinephrine metabolism.     

十二指肠损伤的处理

目的：探讨十二指肠损伤的常见原因及外科处理方法。方法：收集1988年6月至2000年12月我院收治的8例十二指肠严重损伤患者的临床资料,回顾性分析十二指肠严重损伤的原因及外科处理方式。结果：本组8例十二指肠严重损伤,主要的损伤原因为车祸和医源性损伤,均经十二指肠破口与空肠直接行Roux—en-Y吻合,术后恢复顺利,痊愈出院。除1例3．5年后肿瘤复发死亡外,其余病人无并发症及后遗症。经以往各种手术相比较,十二指肠破口与空肠直接Roux-en-Y吻合效果最好。结论：十二指肠损伤常见的原因是车祸和医源性损伤,因十二指肠位置特殊,缺乏典型的临床症状,早期诊断困难。应及早诊断,根据患者发病机制、临床表现、辅助检查及术中探查选择简单而合理的手术方式可提高其治愈率。十二指肠破口与空肠直接行Roux-en．Y吻合,该手术方法简单,创伤轻,疗效好,而且适应于十二指肠各部位的损伤。     

大鼠酒精性肝损伤模型及蛋白表达指纹图谱的建立

目的:建立大鼠酒精性肝损伤模型,以蛋白质芯片技术为实验手段对损伤过程中的大鼠血清及肝脏蛋白质变化进行观察,以期获得损伤过程中的蛋白标志物,建立损伤过程蛋白表达指纹图谱;观察有机硒对大鼠肝脏损伤的防护作用。方法:用食用酒精辅以橄榄油对大鼠进行肝损伤,动态检测大鼠肝重比、血清生化指标,并进行肝组织病理切片观察;应用表面加强激光电离解吸飞行时间质谱技术对大鼠肝损伤过程进行跟踪检测,获得蛋白标志物,同时证实有机硒对肝损伤具有一定的防护作用。结果:肝重比、生化指标及病理切片均表明损伤模型已基本建立,同时验证了有机硒的肝损伤保护作用。在12周的损伤过程中,发现大鼠血清中有4个具有统计学意义的蛋白标志物,其相对分子质量(Mr)分别为7010、8307、11624和14041;在肝组织中发现了2个有统计意义的蛋白标志物,其Mr分别为5931.2和7104.6。结论:建立了大鼠酒精性肝损伤模型,获得了血清及肝脏蛋白标志物,为后期进行临床实验提供了可行的研究方法;同时为有机硒应用于临床进行肝损伤防护奠定了良好的实验基础。     

急性颅脑损伤血凝检查的临床意义

目的：探讨急性颅脑损伤后血凝检查的临床意义。方法：对85例急性颅脑损伤患者伤后不同时间分别测定六项血凝指标,进行比较分析。结果：损伤24小时后血凝指标检测结果与伤后1周、3周比较有显著差异,有统计学意义（P〈0.05）。结论：急性颅脑损伤后的血凝检测结果异常,可对疾病的诊断和治疗提供理论依据。     

急性颅脑损伤血凝检查的临床意义

目的:探讨急性颅脑损伤后血凝检查的临床意义。方法:对85例急性颅脑损伤患者伤后不同时间分别测定六项血凝指标,进行比较分析。结果:损伤24小时后血凝指标检测结果与伤后1周、3周比较有显著差异,有统计学意义(P<0.05)。结论:急性颅脑损伤后的血凝检测结果异常,可对疾病的诊断和治疗提供理论依据。     

全身放射损伤对皮肤伤口成纤维细胞参与组织修复能力的影响

合并全身放射损伤的创伤（放创复合伤）是一种重要而有代表性的难愈性创伤,其难愈机制尚未完全阐明,成纤维细胞是最为重要的组织修复细胞,其辐射敏感性较低,为了明确放创复合伤时合并的放射损伤是否对伤口成纤维细胞有直接损伤作用,以及这些损伤作用对创伤愈合的影响,实验检测了分离,培养的放创复合伤和单纯创伤大鼠皮肤伤口成纤维细胞的增殖,凋亡及其他反映其参与组织修复能力的指标变化,结果发现,在去除全身因素和局部因素,特别是创伤局部细胞因子和细胞外基质对成纤维细胞的反馈作用后,放创复合伤组伤口成纤维细胞增殖力,贴壁力和粘附力均显著弱于单纯创伤组,而成纤维细胞的凋亡率则显著增加,这些细胞表明,全身放射损伤对伤口成纤维细胞有直接损伤作用,使其参与组织修复能力显著受抑,这是合并全身放射损伤时创伤难愈的重要原因。     

5-脂氧合酶（5-LOX）及代谢产物在异氟醚预处理脑保护作用中的研究进展

缺血性脑血管疾病（Ischemia Cerebral Vascular Disease,ICVD）可造成不同程度的神经功能障碍,以其高发病率、高致残率、高复发率、高死亡率严重威胁着人们的身体健康。而脑组织缺血后再灌注损伤即脑缺血再灌注损伤（ischemia-reperfusion injury）是脑缺血性疾病的最主要的损伤原因之一,因此阐明脑缺血再灌注损伤发生发展的病理生理机制、探寻有效的预防保护措施成为当今研究的重点问题。本文回顾、归纳脑缺血再灌注损伤的相关分子机制及异氟醚预处理对脑缺血再灌注损伤的保护作用,分析5-脂氧合酶及其代谢产物在脑缺血再灌注损伤中的作用及其与其他分子的相互关系,旨在探讨5-脂氧合酶及其代谢产物在异氟醚预处理保护脑缺血再灌注损伤中可能起到的作用。为脑缺血再灌注损伤的防治提供更多的理论依据。     

Pathophysiological analysis of combined burn and smoke inhalation injuries in sheep

We investigated the pathophysiological alterations seen with combined burn and smoke inhalation injuries by focusing on pulmonary vascular permeability and cardiopulmonary function compared with those seen with either burn or smoke inhalation injury alone. To estimate the effect of factors other than injury, the experiments were also performed with no injury in the same experimental setting. Lung edema was most severe in the combined injury group. Our study revealed that burn injury does not affect protein leakage from the pulmonary microvasculature, even when burn is associated with smoke inhalation injury. The severity of lung edema seen with the combined injury is mainly due to augmentation of pulmonary microvascular permeability to fluid, not to protein. Cardiac dysfunction after the combined injury consisted of at least two phases. An initial depression was mostly related to hypovolemia due to burn injury. It was improved by a large amount of fluid resuscitation. The later phase, which was indicated to be a myocardial contractile dysfunction independent of the Starling equation, seemed to be correlated with smoke inhalation injury.     

Effects of soluble factors and extracellular matrix components on vascular cell behavior in vitro and in vivo: models of de-endothelialization and repair.

Vessel walls are comprised of several different cell populations residing in and on complex extracellular matrices. Each of the vascular cell types has diverse and sometimes unique functions and morphologies, and each has roles in repair processes following injury. Large vessel endothelial cells are known to respond to denudation injury by sheet migration and proliferation. This is in contrast to the migration through soft tissues with tube formation and subsequent lumen formation exhibited by microvascular endothelial cells in response to injury. Vascular smooth muscle cells of larger vessels respond to injury by migration from the arterial media into the intima, proliferation, and matrix biosynthesis, ultimately causing intimal thickening. Both these cell types exhibit "dysfunctional" phenotypes during their responses to injury. Microvascular cell responses to injury, while extremely variable, are less well documented. Specifically, responses to injury by microvascular endothelial vascular cells appear to be modulated, in part, by the composition and organization of the surrounding matrix as well as by the various soluble factors and cytokines found at sites of injury, suggesting that the extracellular matrix and soluble factors modulate each other's effects on local vascular cell populations following injury.     

Pulmonary changes in a mouse model of combined burn and smoke inhalation-induced injury.

The morbidity and mortality of burn victims increase when burn injury is combined with smoke inhalation. The goal of the present study was to develop a murine model of burn and smoke inhalation injury to more precisely reveal the mechanistic aspects of these pathological changes. The burn injury mouse group received a 40% total body surface area third-degree burn alone, the smoke inhalation injury mouse group received two 30-s exposures of cotton smoke alone, and the combined burn and smoke inhalation injury mouse group received both the burn and the smoke inhalation injury. Animal survival was monitored for 120 h. Survival rates in the burn injury group, the smoke inhalation injury group, and the combined injury group were 70%, 60%, and 30%, respectively. Mice that received combined burn and smoke injury developed greater lung damage as evidenced by histological changes (septal thickening and interstitial edema) and higher lung water content. These mice also displayed more severely impaired pulmonary gas exchange [arterial PO2 (PaO2)/inspired O2 fraction (FiO2)<200]. Lung myeloperoxidase activity was significantly higher in burn and smoke-injured animals compared with the other three experimental groups. Plasma NO2-/NO3-, lung inducible nitric oxide synthase (iNOS) activity, and iNOS mRNA increased with injury; however, the burn and smoke injury group exhibited a higher response. Severity of burn and smoke inhalation injury was associated with more pronounced production of nitric oxide and accumulation of activated leukocytes in lung tissue. The murine model of burn and smoke inhalation injury allows us to better understand pathophysiological mechanisms underlying cardiopulmonary morbidity secondary to burn and smoke inhalation injury.     

Photobiomodulation therapy for repeated closed head injury in rats

Repeated traumatic brain injury, leads to cumulative neuronal injury and neurological impairments. There are currently no effective treatments to prevent these consequences. Growing interest is building in the use of transcranial photobiomodulation (PBM) therapy to treat traumatic brain injury. Here, we examined PBM in a repeated closed head injury (rCHI) rat model. Rats were administered a total of three closed head injuries, with each injury separated by 5 days. PBM treatment was initiated 2 hours after the first injury and administered daily for a total of 15 days. We found that PBM‐treated rCHI rats had a significant reduction in motor ability, anxiety and cognitive deficits compared to CHI group. PBM group showed an increase of synaptic proteins and surviving neurons, along with a reduction in reactive gliosis and neuronal injury. These findings highlight the complexity of gliosis and neuronal injury following rCHI and suggest that PBM may be a viable treatment option to mitigate these effects and their detrimental consequences.     

基于磁共振多b值弥散加权成像对严重胸外伤预后的预测

目的:探讨基于磁共振(Magnetic Resonance Imaging,MRI)多b值弥散加权成像(Diffusion Weighted Imaging,DWI)对严重胸外伤预后的预测价值。方法:2018年2月-2020年6月选择在本院诊治的严重胸外伤患者76例(开放性损伤38例,闭合性损伤38例),所有患者都给予常规MRI扫描、多b值DWI扫描,记录成像质量与特征,判断预测价值。结果:所有患者都在胸外伤后3 d内进行检查,开放性损伤与闭合性损伤患者的MRI图像质量优良率都为100.0%,符合诊断要求。开放性损伤患者的多b值DWI之D*值、f值都显著高于闭合性损伤患者,而D值显著低于闭合性损伤患者,对比差异都有统计学意义(P<0.05)。在76例患者中,病理判断为胸腔后方韧带复合体1级损伤38例,2级损伤30例,3级损伤8例。MRI诊断为1级损伤39例,2级损伤31例,3级损伤6例,MRI诊断的准确性为93.4%。结论:基于MRI多b值DWI能清晰显示严重胸外伤的组织损伤情况,也能真实反映组织的微环境变化特征,能有效预测后方韧带复合体的损伤情况。     

入伍新训中膝关节损伤的特点与防治研究

目的：通过对某部新入伍官兵训练中膝关节损伤发生原因、特点进行流行性病学调查和分析,为合理训练,预防损伤发生和 治疗相关伤病提供指导依据。方法：对某部2013 年度450 名新入伍官兵的训练伤发病情况进行统计分析,重点分析膝关节损伤 发生率、伤病类型和致伤原因,并对其严重者进行关节镜治疗,观察和分析术后随访效果。结果：某部新兵的训练伤发生率为 20.0%。以关节急性扭伤最为多见,占81.1%。其中膝关节损伤共发生32 例,占训练伤发病率为7.1%,占训练伤发病率43.8%,其 中膝关节周围肌肉损伤20 例、交叉韧带损伤1 例、半月板损伤9 例、侧副韧带损伤2 例。致伤率最高的前3 位科目是5000 米负 重跑、跨越障碍训练、格斗训练,共27 例,占膝关节训练伤总数的84.4%。所有受伤患者中,12 例行手术治疗,20 例给予石膏、支具 固定、休息等保守治疗。经随访所有患者均得到较好的功能恢复。结论：对于新兵膝关节训练伤预防工作非常重要,避免致残;关 节镜手术技术的进步对于膝关节军事训练伤治疗有良好的效果。