Neuron-glia communication: metallothionein expression is specifically up-regulated by astrocytes in response to neuronal injury

Recent data suggests that metallothioneins (MTs) are major neuroprotective proteins within the CNS. In this regard, we have recently demonstrated that MT-IIA (the major human MT-I/-II isoform) promotes neural recovery following focal cortical brain injury. To further investigate the role of MTs in cortical brain injury, MT-I/-II expression was examined in several different experimental models of cortical neuron injury. While MT-I/-II immunoreactivity was not detectable in the uninjured rat neocortex, by 4 days, following a focal cortical brain injury, MT-I/-II was found in astrocytes aligned along the injury site. At latter time points, astrocytes, at a distance up to several hundred microns from the original injury tract, were MT-I/-II immunoreactive. Induced MT-I/-II was found both within the cell body and processes. Using a cortical neuron/astrocyte co-culture model, we observed a similar MT-I/-II response following in vitro injury. Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no change in MT-I/-II expression. This suggests that MT induction was specifically elicited by neuronal injury. Based upon recent reports indicating that MT-I/-II are major neuroprotective proteins within the brain, our results provide further evidence that MT-I/-II plays an important role in the cellular response to neuronal injury.     

Focus: Preventive Medicine: Before the Bullets Fly: The Physician’s Role in Preventing Firearm Injury

Firearm injury is a disease that is disproportionately prevalent in the United States. When a bullet hits a human being, it brings together multiple structural determinants of health into one acute, life-changing event. Firearm injury can lead to long-term mental and physical challenges for individuals, families, and communities. Despite the impact of this disease, physicians often underestimate their role in not only treating but also preventing firearm injury. Physicians can intervene through screening, counseling, community engagement, and advocacy, and can mobilize the health care systems they serve to engage with injury prevention. Physicians also play a key role in expanding the knowledge base on firearm injury through much-needed research on the epidemiology, context, and outcomes of firearm injury. When we treat firearm injury as a disease, we can develop and implement interventions from the clinic to the statehouse that can curb profound harms. This work and these opportunities belong not only to emergency physicians and trauma surgeons, but to all fields that evaluate and assess patients over the life course.     

低温在脊髓损伤治疗中应用的研究进展

脊髓损伤多由高空坠落、车祸、运动冲击等原因引起,是脊柱外科的一种常见疾病,至今仍是一个治疗难题。低温疗法是一种重要的物理治疗手段,以多种机制减少脊髓损伤后有害因素的产生,是一种有效的脊髓保护途径。其在脊髓损伤的研究中表现出很好的效果,为脊髓损伤的治疗提供了新的思路,然而也发现一些低温治疗导致的全身性或某些系统为主的不良影响,需要我们进一步研究和解决,以期达到更好的治疗效果。本文就低温治疗用于脊髓损伤应用中的研究进展进行综述。     

Towards reducing impact-induced brain injury: lessons from a computational study of army and football helmet pads

We use computational simulations to compare the impact response of different football and U.S. Army helmet pad materials. We conduct experiments to characterise the material response of different helmet pads. We simulate experimental helmet impact tests performed by the U.S. Army to validate our methods. We then simulate a cylindrical impactor striking different pads. The acceleration history of the impactor is used to calculate the head injury criterion for each pad. We conduct sensitivity studies exploring the effects of pad composition, geometry and material stiffness. We find that (1) the football pad materials do not outperform the currently used military pad material in militarily relevant impact scenarios; (2) optimal material properties for a pad depend on impact energy and (3) thicker pads perform better at all velocities. Although we considered only the isolated response of pad materials, not entire helmet systems, our analysis suggests that by using larger helmet shells with correspondingly thicker pads, impact-induced traumatic brain injury may be reduced.     

Eupatilin alleviates inflammatory response after subarachnoid hemorrhage by inhibition of TLR4/MyD88/NF-κB axis

Early brain injury (EBI) is associated with the adverse prognosis of subarachnoid hemorrhage (SAH) patients. The key bioactive component of the Chinese herbal medicine Artemisia asiatica Nakai (Asteraceae) is eupatilin. Recent research reports that eupatilin suppresses inflammatory responses induced by intracranial hemorrhage. This work is performed to validate whether eupatilin can attenuate EBI and deciphers its mechanism. A SAH rat model was established by intravascular perforation in vivo. At 6 h after SAH in rats, 10 mg/kg eupatilin was injected into the rats via the caudal vein. A Sham group was set as the control. In vitro, BV2 microglia was treated with 10 μM Oxyhemoglobin (OxyHb) for 24 h, followed by 50 μM eupatilin treatment for 24 h. The SAH grade, brain water content, neurological score, and blood-brain barrier (BBB) permeability of the rats were measured 24 h later. The content of proinflammatory factors was detected via enzyme-linked immunosorbent assay. Western blot analysis was conducted to analyze the expression levels of TLR4/MyD88/NF-κB pathway-associated proteins. In vivo, eupatilin administration alleviated neurological injury, and decreased brain edema and BBB injury after SAH in rats. Eupatilin markedly reduced the levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and suppressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in the SAH rats' cerebral tissues. Eupatilin treatment also reduced the levels of IL-1β, IL-6, and TNF-α, and repressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in OxyHb-induced BV2 microglia. Additionally, pyrrolidine dithiocarbamate or resatorvid enhanced the suppressive effects of eupatilin on OxyHb-induced inflammatory responses in BV2 microglia. Eupatilin ameliorates SAH-induced EBI via modulating the TLR4/MyD88/NF-κB pathway in rat model.     

Paleoepidemiological patterns of interpersonal aggression in a prehistoric central California population from CA‐ALA‐329

Interpersonal aggression is assessed paleoepidemiologically in a large skeletal population from the CA‐ALA‐329 site located on the southeastern side of San Francisco Bay, California. This comprehensive analysis included all currently recognized skeletal criteria, including craniofacial fracture, projectile injury, forearm fracture, and perimortem bone modification. Craniofacial injury is moderately common, showing an adult prevalence of 9.0% with facial lesions accounting for >50% of involvement. Clinical studies suggest that such separate evaluation of facial involvement provides a useful perspective for understanding patterns of interpersonal aggression. In this group male facial involvement is significantly greater than in females, paralleling the pattern found widely in contemporary populations as well as in African apes. When compared to other North American skeletal samples the prevalence of adult cranial vault injury (3.3%) and especially projectile injury (4.4%) are quite high. However, well documented populations from southern California show markedly higher prevalence for both types of skeletal markers of aggression. Forearm fracture is also assessed using a rigorous radiographic methodology and results suggest that these injuries are not reliable indicators of interpersonal aggression. Lastly, perimortem bone modification was not observed in this population, although it has been recorded from other (older) sites nearby. This study provides an evaluation of multiple skeletal markers of interpersonal aggression in the largest sample from a single site yet reported in North America and, joined with consideration of cultural context, helps further illuminate both geographic and temporal patterns of interpersonal aggression in California. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Temporal expression profile of CXC chemokines in serum of patients with spinal cord injury

Chemokines, a subclass of cytokine superfamily have both pro-inflammatory and migratory role and serve as chemoattractant of immune cells during the inflammatory responses ensuing spinal cord injury (SCI). The chemokines, especially CXCL-1, CXCL-9, CXCL-10 and CXCL-12 contribute significant part in the inflammatory secondary damage of SCI. Inhibiting chemokine’s activity and thereby the secondary damage cascades has been suggested as a chemokine-targeted therapeutic approach to SCI. To optimize the inhibition of secondary injury through targeted chemokine therapy, accurate knowledge about the temporal profile of these cytokines following SCI is required. Hence, the present study was planned to determine the serum levels of CXCL-1, CXCL-9, CXCL-10 and CXCL-12 at 3–6 h, 7 and 28 days and 3 m after SCI in male and female SCI patients (n = 78) and compare with age- and sex-matched patients with non-spinal cord injuries (NSCI, n = 70) and healthy volunteers (n = 100). ANOVA with Tukey post hoc analysis was used to determine the differences between the groups. The data from the present study show that the serum level of CXCL-1, CXCL-9 and CXCL-10 peaked on day 7 post-SCI and then declined to the control level. In contrast, significantly elevated level of CXCL-12 persisted for 28 days post SCI. In addition, post-SCI expression of CXCL-12 was found to be sex-dependent. Male SCI patients expressed significantly higher CXCL-12 when compared to control and SCI female. We did not observe any change in chemokines level of NSCI. Further, the age of the patients did not influence chemokines expression after SCI. These observations along with SCI-induced CSF-chemokine level should contribute to the identification of selective and temporal chemokine targeted therapy after SCI.     

冲击波负压对大鼠肺致伤效应的初步观察

观察了不同的冲击波负压峰值对大鼠肺的影响。各种条件下的冲击波负压值可由负压发生装置来模拟调节,这种装置可满足化爆、核爆和爆炸性减压下负压参数的一般要求,参数稳定,重复性好。冲击波负压峰值范围为-13～-90kPa,下降时间为1～90ms,持续时间为14～2 000ms。6组Wistar系大鼠,分别暴露在-47.2～-84.0kPa的冲击波负压环境中,伤后立即解剖动物,重点观察肺伤情。实验结果显示,在上述冲击波负压环境中,肺可出现从无伤至极重度伤;出血、充血以及肺表面压痕酷似肺冲击伤的病理表现。随着冲击波负压峰值的变化,各组肺伤情亦随着变化,冲击波负压峰值(△P)和减压倍数(P_i/P_a)分别与肺出血面积和动物死亡率相关显著或非常显著。本实验提示,一定条件下的冲击波负压具有明显的致伤作用,且伤情变化范围与超压所致肺伤情变化范围相同,超压和冲击波负压在一定条件下可通过伤情指标等效。     

Could lowering the tackle height in rugby union reduce ball carrier inertial head kinematics?

There is mounting evidence of reduced long-term cognitive ability in rugby players, even in those without a reported history of concussion. The tackle height law is an area of controversy. However, little is known about the effects of repetitive inertial head loading in rugby. Furthermore, the magnitude and influencing factors for head kinematics are generally unknown. In this exploratory study, 45 multibody front-on shoulder tackles simulated with the MADYMO pedestrian model and 20 staged rugby tackles executed by professional rugby players in a marker-based 3D motion laboratory were used to assess the effect of tackle height on ball carrier head kinematics. The peak resultant head linear accelerations, angular accelerations and change in angular velocities were measured and examined. The results suggest that tackle height strongly affects the head kinematics experienced by the ball carrier. In particular, higher ball carrier head kinematic values were identified for upper trunk tackles compared to mid/lower trunk tackles in both the multibody simulations and the staged rugby tackles. Average ball carrier peak resultant head linear acceleration, angular acceleration and change in angular velocity values for upper trunk tackles were greater than for mid/lower trunk tackles by a factor of 1.5, 2.5 and 1.7, in the multibody simulations, respectively, and 1.8 (p = 0.102), 2.2 (p = 0.025) and 2.3 (p = 0.004), in the staged tackles, respectively. The results of the study support the proposition of lowering the current tackle height laws to below the chest.     

NOGO-A immunolabeling is present in glial cells and some neurons of the recovering lumbar spinal cord in lizards

The transected lumbar spinal cord of lizards was studied for its ability to recover after paralysis. At 34 days post-lesion about 50% of lizards were capable of walking with a limited coordination, likely due to the regeneration of few connecting axons crossing the transection site of the spinal cord. This region, indicated as “bridge”, contains glial cells among which oligodendrocytes and their elongation that are immunolabeled for NOGO-A. A main reactive protein band occurs at 100–110 kDa but a weaker band is also observed around 240 kDa, suggesting fragmentation of the native protein due to extraction or to physiological processing of the original protein. Most of the cytoplasmic immunolabeling observed in oligodendrocytes is associated with vesicles of the endoplasmic reticulum. Also, the nucleus is labeled in some oligodendrocytes that are myelinating sparse axons observed within the bridge at 22–34 days post-transection. This suggests that axonal regeneration is present within the bridge region. Immunolabeling for NOGO-A shows that the protein is also present in numerous reactive neurons, in particular motor-neurons localized in the proximal stump of the transected spinal cord. Ultrastructural immunolocalization suggests that NOGO is synthesized in the ribosomes of these neurons and becomes associated with the cisternae of the endoplasmic reticulum, probably following a secretory pathway addressed toward the axon. The present observations suggest that, like for the regenerating spinal cord of fish and amphibians, also in lizard NOGO-A is present in reactive neurons and appears associated to axonal regeneration and myelination.     

Noninvasive monitoring of citrate, acetate, lactate, and renal medullary osmolyte excretion in urine as biomarkers of exposure to ischemic reperfusion injury

Injury during the transplant process affects the alloantigen-dependent factors and the alloantigen-independent processes of "chronic" rejection. Consequently, the determination of reliable parameters for the assessment of ischemic damage is essential for the prediction of renal changes after ischemia/reperfusion injury. The aim of this study was to assess the ability of (1)H NMR spectroscopy to predict the early graft dysfunction in an ischemia/reperfusion model after preservation in two standard preservation solutions, Euro-Collins (EC) and University of Wisconsin (UW). The second aim was to specify the role of the UW solution in preventing renal medullary injury. Urine and plasma samples from three experimental groups were examined during 2 weeks: control group (n = 5), EC group (cold flushed and 48-h cold storage of kidney in EC and autotransplantation, n = 12), and UW group (cold flushed and 48-h cold storage of kidney in UW and autotransplantation; n = 12). We also examined these kidneys 30-40 min after implantation and on the sacrifice day. Creatinine clearance was significantly reduced in the EC group during the second week. Fractional excretion of sodium and urine N-acetyl-beta-d-glucosaminidase activity were improved but not significantly different in the preserved groups. Urinary concentrations of the alpha-class glutathione S-transferase were significantly greater in the EC group during the first week after transplantation. The most relevant resonances for evaluating renal function after transplantation determined by (1)H NMR spectroscopy were those arising from citrate, dimethylamine (DMA), lactate, and acetate in urine and trimethylamine-N-oxide (TMAO) in urine and plasma. These findings suggest that graft dysfunction is associated with damage to the renal medulla determined by TMAO release in urine and plasma associated with DMA and acetate excretion. Citrate is also a urinary marker that can discriminate kidneys with a favorable evolution. Our results suggest that (1)H NMR spectroscopy is an efficient technique for detecting ischemic damage when accurate and precise data on graft injury is required. In addition, this study outlines the specific impact of the UW solution against injury to the renal medulla.     

脉冲1 064 nm激光视网膜损伤动物模型的建立

目的:建立脉冲1 064 nm Nd:YAG激光致视网膜出血性损伤及非出血性损伤动物模型,为治疗药物评价提供技术基础.方法:应用自由振荡脉冲及调Q脉冲1 064 nm激光照射青紫蓝灰兔视网膜,通过在光路中加人透镜获得直径200μm眼底光斑,加入衰减片改变角膜入射激光能量.照射即刻对损伤应用检眼镜进行实时观察,并用眼底相...     

Species-dependent neuroprotection by activated protein C mutants with reduced anticoagulant activity

Activated protein C (APC) is a protease with anticoagulant and cytoprotective activities. APC is neuroprotective in rodent models of stroke. But, an APC variant with reduced anticoagulant activity, 3K3A-APC, compared to wild-type APC shows greater neuroprotection with no risk for bleeding in stroke models. To determine whether 3K3A-APC exhibits species-dependent neuroprotection similar to that as seen with wild-type APC, we studied murine and human recombinant 3K3A-APC mutants which show approximately 80% reduced anticoagulant activity. Murine 3K3A-APC (0.2 mg/kg i.v.) administered at 4 h after embolic stroke improved substantially functional outcome and reduced by 80% the infract volume 7 days after stroke. Human 3K3A-APC was neuroprotective after embolic stroke in mice, but at significantly higher concentrations (i.e. 2 mg/kg i.v.). Species-dependent neuroprotection, i.e. murine > human 3K3A-APC, was confirmed in a mouse model of permanent middle cerebral artery occlusion. Human 3K3A-APC had by fivefold greater cytoprotective activity than murine 3K3A-APC in oxygen-glucose deprivation model in human brain endothelial cells, whereas murine 3K3A-APC was by 2.5-fold more potent than human 3K3A-APC in a mouse model of NMDA-induced neuronal apoptosis. Thus, 3K3A-APC exhibits species-dependent neuroprotection which should be taken into account when designing human trials for ischemic stroke with APC mutants.     

缺血预适应对大鼠肢体缺血/再灌注后肺损伤的影响

目的:观察肢体缺血预适应对大鼠肢体缺血/再灌注(I/R)后肺损伤的影响并探讨其机制。方法:将雄性Wistar大鼠随机分为4组(n=8):对照组(C),肢体缺血/再灌注组(LI/R),缺血预适应组(IPC)和L-NAME组。各组大鼠均于肢体缺血4h再灌注4h处死,分别测定其动脉血氧分压(PaO2)和二氧化碳分压(PaCO2),血浆及肺组织丙二醛(MDA)、一氧化氮(NO)、内皮素(ET)含量,计算血浆NO/ET比值;以及肺湿干比(W/D)、肺系数(LI),肺组织髓过氧化物酶(MPO)含量。结果:大鼠LI/R后4h,PaO2明显降低;W/D、LI、血浆及肺组织的MDA、NO、ET和肺组织MPO活性均明显增加,而血浆NO/ET比值明显减小。与LI/R组比较,IPC组各项损伤指标明显减轻,NO水平升高,血浆NO/ET比值明显增大。与对照组和IPC组比较,L-NAME处理组,各项损伤指标数值明显增加,NO水平降低;血浆NO/ET比值明显减小,差异均具有显著性。各组大鼠PaCO2的变化无显著性。结论:缺血预适应对肢体缺血/再灌注后肺损伤具有保护作用,其机制可能与内源性NO合成增加有关。     

内皮素-1在神经源性肺水肿中的作用

目的:探讨内皮素-1(ET-1)在神经源性肺水肿(NPE)发病机理中的作用.方法:采用Marmarous 闭合性颅脑损伤模型致大鼠重度、弥漫性颅脑损伤,检测血浆、肺匀浆中ET-1的含量,并用免疫组化方法检测肺ET-1的表达.结果:大鼠重度弥漫性颅脑损伤后1 h起血浆及肺匀浆中ET-1含量增加,6 h达高峰,24 h以后略有下降,但是,在48 h内一直维持在较高水平(P<0.05).病理学检查显示:伤后1h起肺毛细血管扩张、充血;肺间隔增宽,有以中性粒细胞及单个核细胞为主的白细胞浸润,6 h最明显;24 h、48 h肺充血、肿胀,肺泡腔内充满大量嗜伊红的蛋白渗出物.免疫组化显示:ET-1在实验组较对照组阳性表达增强,光密度值增高,以6 h最显著.结论:ET-1介导的炎性损伤机制在神经源性肺水肿中可能起重要作用.     

牛磺酸对大鼠肢体缺血/再灌注后肺组织损伤的保护作用

目的:观察大鼠肢体缺血再灌注(LIR)后肺组织形态学的变化及牛磺酸对其影响.方法:Wistar大鼠随机分为3组,对照组(control)、缺血/再灌注组(LIR)、牛磺酸 缺血/再灌注组(Tau LIR),各组动物通过大体、光镜和透射电镜观察肺组织形态学变化,并测定肺系数和肺通透指数及肺组织活性氧和MDA含量.结果:大鼠LIR后肺组织出现以肺泡毛细血管膜通透性增加为特征的组织细胞损伤,光镜下显示毛细血管扩张充血、血管周围间隙增大、肺泡腔中有大量蛋白渗出物,电镜下可见肺泡上皮细胞之间、毛细血管内皮之间的紧密连接松解;肺系数和肺通透指数升高;肺组织活性氧及MDA含量增加.提前给予外源性牛磺酸可使肺组织损伤变化减轻.结论:牛磺酸对大鼠LIR后肺损伤有保护作用,其保护机理之一与其抗氧化,保护细胞之间的紧密连接有关.     

黄鼠与大鼠离体心脏预缺血处理对缺血再灌损伤的保护作用

本文用黄鼠和大鼠离体心脏比较了两种预缺血处理方案对随后缺血再灌损伤的作用。用Ｌａｎｇｅｎｄｏｒｆｆ方法灌流秋季未入眠的达乌尔黄鼠和Ｗｉｓｔａｒ大鼠离体心脏,以冠脉流出液中肌酸激酶（ＣＫ）释放活性、心律失常发生率、心功能恢复等为指标,检验不同预缺血处理时间对随后缺血再灌损伤的影响。标本平衡１０ｍｉｎ后对照组的两种动物经受缺灌１５ｍｉｎ再灌１５ｍｉｎ预缺血处理,接着进行两次缺灌１０ｍｉｎ再灌１０ｍｉｎ     

A multi-body dynamics study on a weight-drop test of rat brain injury

Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health problem worldwide. Rats are a well-established animal analogue for study of TBI and the weight-drop impact-acceleration (WDIA) method is a well-established model in rats for creating diffuse TBI, the most common form of TBI seen in humans. However, little is known of the biomechanics of the WDIA method and, to address this, we have developed a four-degrees-of-freedom multi-body mass-spring-damper model for the WDIA test in rats. An analytical expression of the maximum skull acceleration, one of the important head injury predictor, was derived and it shows that the maximum skull acceleration is proportional to the impact velocity but independent of the impactor mass. Furthermore, a dimensional analysis disclosed that the maximum force on the brain and maximum relative displacement between brain and skull are also linearly proportional to impact velocity. Additionally, the effects of the impactor mass were examined through a parametric study from the developed multi-body dynamics model. It was found that increasing impactor mass increased these two brain injury predictors.