Oxidative stress following traumatic brain injury in rats: quantitation of biomarkers and detection of free radical intermediates

Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F(2alpha), was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N:-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.     

Protein carbonylation after traumatic brain injury: cell specificity,regional susceptibility,and gender differences

Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague–Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional and protein specificity in protein carbonylation after TBI. The marked increase in carbonylation seen in ependymal layers distant from the lesion suggests a mechanism involving the transmission of a cerebral spinal fluid-borne factor to these sites. Furthermore, this process is affected by gender, suggesting that hormonal mechanisms may serve a protective role against oxidative stress.     

Traumatic brain injury and bone healing: radiographic and biomechanical analyses of bone formation and stability in a combined murine trauma model

Introduction:The combination of traumatic brain injury (TBI) and long-bone fractures has previously been reported to lead to exuberant callus formation. The aim of this experimental study was to radiographically and biomechanically study the effect of TBI on bone healing in a mouse model.Materials and methods:138 female C57/Black6N mice were assigned to four groups (fracture (Fx) / TBI / combined trauma (Fx/TBI) / controls). Femoral osteotomy and TBI served as variables: osteotomies were stabilized with external fixators, TBI was induced with controlled cortical impact injury. During an observation period of four weeks, in vivo micro-CT scans of femora were performed on a weekly basis. Biomechanical testing of femora was performed ex vivo.Results:The combined-trauma group showed increased bone volume, higher mineral density, and a higher rate of gap bridging compared to the fracture group. The combined-trauma group showed increased torsional strength at four weeks.Discussion:TBI results in an increased formation of callus and mineral density compared to normal bone healing in mice. This fact combined with a tendency towards accelerated gap bridging leads to increased torsional strength. The present study underscores the empirical clinical evidence that TBI stimulates bone healing. Identification of underlying pathways could lead to new strategies for bone-stimulating approaches in fracture care.     

二尖瓣置换术后左心室破裂2例并文献复习

目的：总结二尖瓣置换术后左心室破裂2例临床经验教训,方法：回顾性分析我院2006,1．2009,12二尖瓣置换术后左心室破裂2例的临床资料,两例均在监护室里发生突然大出血,紧急输血,输液,机械呼吸,抗休克治疗,并行开胸手术。结果：一例心外修补抢救成功,术后2周顺利出院,一例CPB下心内外修补,因低心排综合症死亡。结论：左心室破裂是二尖瓣置换术最严重的并发症,一旦发生死亡率极高,因此预防,避免其相关因素更关键：     

道路交通事故致胫腓骨骨折的特点及救治

目的：总结交通事故伤中胫腓骨骨折的流行病学分类、特点及救治注意事项。方法：对136例交通事故伤中胫腓骨骨折患者的临床资料进行回顾性分析。结果：交通事故致胫腓骨骨折以多发伤及复合伤多见,经早期彻底清创、恰当的骨折固定、抗生素应用等,治愈77例,截肢2例,伤口浅表感染6例,骨髓炎1例。结论：交通事故伤中胫腓骨骨折大多伤情严重,感染率高,且开放性居多,早期及时选择合适的治疗方法是取得良好预后的关键。     

大鼠脑损伤后非损伤区域缺氧诱导因子与乳酸的变化研究

目的:研究大鼠脑损伤后非损伤区域缺氧诱导因子(hypoxia-inducible factor-1α,HIF-1α)与乳酸的表达变化。方法:取雄性SD大鼠36只,体重200-300g,参照统计学随机数字表将大鼠随机平均分为正常对照组(6只)、假手术组(6只)、造模组(24只),3组,造模组分四个时间点12h、72h、1w、2w处死动物(每时间点6只)。使用立体定位仪和液压打击装置,靶向打击大脑中动脉,造大鼠脑外伤模型。采用免疫组织化学法检测脑外伤后不同时间点损伤临近区域脑组织中HIF-1α蛋白表达及乳酸含量的变化。结果:正常组和假手术组脑组织神经细胞HIF-1α表达和乳酸含量无明显变化,而模型组损伤临近区域HIF-1α的表达及乳酸含量的变化规律基本一致,12 h时增多,72h时达到高峰,1w表达下降至2w时恢复正常。造模组12h、72h、1w3个亚组与正常对照组比较差异具有统计学意义p<0.01,造模组2w亚组与正常对照组比较差异无统计学意义p>0.01。结论:脑外伤后非损伤区域也有缺血、缺氧的改变,可能与脑外伤后的脑萎缩有相关性。     

道路交通事故致胫腓骨骨折的特点及救治

目的:总结交通事故伤中胫腓骨骨折的流行病学分类、特点及救治注意事项。方法:对136例交通事故伤中胫腓骨骨折患者的临床资料进行回顾性分析。结果:交通事故致胫腓骨骨折以多发伤及复合伤多见,经早期彻底清创、恰当的骨折固定、抗生素应用等,治愈77例,截肢2例,伤口浅表感染6例,骨髓炎1例。结论:交通事故伤中胫腓骨骨折大多伤情严重,感染率高,且开放性居多,早期及时选择合适的治疗方法是取得良好预后的关键。     

A phenomenological model for atherosclerotic plaque growth and rupture

The objective of this communication is to develop a computer-based framework for the overall coupled phenomena leading to growth and rupture of atherosclerotic plaques. The modeling is purposely simplified to expose the dominant phenomenological controlling mechanisms, and their coupled interaction. The main ingredients of the present simplified modeling approach, describing the events that occur due to the presence and oxidation of excess low-density lipoprotein (LDL) in the intima, are: (i) adhesion of monocytes to the endothelial surface, which is controlled by the intensity of the blood flow and the adhesion molecules stimulated by the excess LDL, (ii) penetration of the monocytes into the intima and subsequent inflammation of the tissue, and (iii) rupture of the plaque accompanied with some degree of thrombus formation or even subsequent occlusive thrombosis. The set of resulting coupled equations, each modeling entirely different physical events, is solved using an iterative staggering scheme, which allows the equations to be solved in a computationally convenient decoupled fashion. Theoretical convergence properties of the scheme are given as a function of physical parameters involved. A numerical example is given to illustrate the modeling approach and an a priori prediction for time to rupture as a function of arterial geometry, diameter of the monocyte, adhesion stress, bulk modulus of the ruptured wall material, blood viscosity, flow rate and mass density of the monocytes.