Expression of intestinal CD40 after experimental traumatic brain injury in rats

Background

Nuclear factor kappa B (NF-κB) has been shown to be activated in the intestine after traumatic brain injury (TBI), and results in gastrointestinal mucosal injury. In addition, CD40 has a major role in the activation of NF-κB and is up-regulated in inflammatory bowel disease. However, we found no study in the literature investigating the intestinal expression of CD40 after TBI. Hence, we designed the current study to explore the intestinal expression pattern of CD40 after TBI in rats. We hypothesized that CD40 could mediate inflammation and ultimately contribute to acute intestinal mucosal injury after TBI.

Methods

We randomly divided rats into control and TBI groups at 3, 6, 12, 24, and 72 h, respectively. We assessed the expression of CD40 by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical study, and detected the levels of tumor necrosis factor-α (TNF-α), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay.

Results

The mRNA and protein levels of -CD40 increased by 3 and 6 h, peaked at 6 and 12 h, and remained elevated until 24 and 72 h post-injury, respectively. Levels of TNF-α, VCAM-1, and ICAM-1 also markedly increased in jejunum tissue after TBI. Interestingly, there was a positive relationship between the expression of CD40 and that of TNF-α, VCAM-1, and ICAM-1.

Conclusions

CD40 could be markedly elevated in intestine after TBI in rats, and it might have an important role in the pathogenesis of acute intestinal mucosal injury mediated by inflammatory response.     

Effect of Intrathecal Baclofen Concentration on Spasticity Control: Case Series

Background/Objective: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.     

香芹酚通过抑制脑水肿与氧化应激反应保护大鼠 颅脑损伤

目的 探讨香芹酚对大鼠颅脑损伤（TBI）的保护作用及其机制。方法 SD大鼠50只,随机分为5组:假手术组、模型组、低剂量香芹酚（10 mg/kg）组、中剂量香芹酚（20 mg/kg）组、高剂量香芹酚（40 mg/kg）组,每组10只。Feeney氏自由落体法制备TBI模型,造模后1、3、7 d采用改良神经功能损害程度评分（mNSS）评估神经功能,干湿法测定脑组织含水量;ELISA法检测氧化应激因子丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、过氧化氢酶（CAT）以及化学定量法检测一氧化氮（NO）含量及一氧化氮合酶（NOS）活性。结果 香芹酚能显著改善大鼠TBI后神经功能,显著减轻TBI后脑水肿,显著降低损伤脑组织MDA、NO和NOS含量,显著增加损伤脑组织SOD、CAT和GSH含量。结论 香芹酚可通过减轻大鼠TBI后脑水肿、抑制氧化应激从而发挥神经保护作用。     

颅脑损伤后发生脑积水的危险因素分析

目的 探讨颅脑损伤后发生脑积水的危险因素。方法 回顾性分析2011年1月至2015年12月收治的380例颅脑损伤的临床资料,其中行去骨瓣减压术62例;采用多因素Logistic回归分析检验危险因素。结果 380例颅脑损伤中,继发脑积水63例,多因素Logistic回归分析显示术前GCS评分≤8分,蛛网膜下腔出血,硬脑膜下积液及去骨瓣减压术是发生脑积水的独立危险因素（P<0.05）。62例去骨瓣减压术中,发生脑积水20例,多因素Logistic回归分析显示双侧去骨瓣减压术,骨窗面积较大及二次手术是去骨板减压术后发生脑积水的独立危险因素（P<0.05）。结论 颅脑损伤后昏迷程度,蛛网膜下腔出血,双侧去骨瓣减压术,二次手术等均为发生脑积水的危险因素。     

Cognitive deficits develop 1 month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge

Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline.Statement of SignificanceTraumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here, we show that primed microglia and astrocytes developed in mice 1 month following moderate diffuse TBI, coinciding with cognitive deficits that were not initially evident after injury. Additionally, TBI-induced glial priming may adversely affect the ability of glia to appropriately respond to immune challenges, which occur regularly across the lifespan. Indeed, we show that an acute immune challenge augmented microglial reactivity and cognitive deficits. This idea may provide new avenues of clinical assessments and treatments following TBI.     

Traumatic anterior cerebral artery aneurysms and management options in the endovascular era

Traumatic anterior cerebral artery (ACA) pseudoaneurysms are a challenge to manage. Difficult diagnosis, delayed presentation and catastrophic outcomes contribute to the overall prognosis of traumatic intracranial aneurysms. Clipping or coiling of the aneurysm and/or parent vessel occlusion are the treatment options. However, surgery and coiling both may be difficult due to limited access and the need for parent vessel preservation. Rarely, these aneurysms must be managed conservatively. We present four patients with traumatic ACA aneurysms admitted to our center in the last 10 months. Three patients had pseudoaneurysms of the distal ACA and one had an aneurysm arising from a cortical branch of the ACA. Their clinical presentations and management, along with outcomes, are discussed as well as the dilemmas associated with them. Three patients were managed by clipping and coiling while one was managed conservatively. The diagnosis was made relatively early in three patients while delayed subarachnoid hemorrhage led to diagnosis in the fourth. Although the overall prognosis remains grim, with high mortality and morbidity rates, both microsurgical and interventional management of these traumatic aneurysms may be useful, if detected early before rupture. Expectant management and surveillance may be required in a select group of patients.     

吉林省颅脑损伤后器官捐献140例临床分析

目的总结吉林省颅脑损伤后器官捐献者的临床资料及相关经验,为进一步提高公民逝世后器官捐献率提供依据。 方法对2013年1月至2015年12月期间吉林省公民逝世后器官捐献的临床资料进行回顾性分析和总结。 结果3年中,吉林省共有140例公民逝世后器官捐献,皆来源于颅脑损伤供者,共捐献器官数量619个,包括108个肝脏、269个肾脏、3个心脏、5个肺脏等。创伤性颅脑损伤供者81例,约占57.9%;非创伤性颅脑损伤供者,包括脑出血、脑干出血、蛛网膜下腔出血等共59例,约占42.1%。车祸导致的颅脑创伤供者65例,约占80.2%;摔伤导致的颅脑创伤供者11例,约占13.6%;高处坠落导致的颅脑创伤供者5例,约占6.2%。创伤性颅脑损伤供者捐献了63个肝脏、160个肾脏、2个心脏、3个肺脏。颅脑创伤供者平均年龄低于脑出血供者。 结论颅脑损伤器官捐献者是公民逝世后器官捐献的重要来源,加强颅脑损伤潜在器官捐献者转化为实际捐献者,是缓解器官短缺的重要途径。     

Prognostic factors of early outcome and discharge status in patients undergoing surgical intervention following traumatic intracranial hemorrhage

Over the past several decades, the rate of traumatic brain injury (TBI)-related emergency room visits in the United States has steadily increased, yet mortality in these patients has decreased. This improvement in outcome is largely due to advances in prehospital care, intensive care unit management, and the effectiveness of neurosurgical procedures, such as decompressive craniectomies. It is imperative to identify clinical factors predictive of patients who benefit from early mobilization of resources and operative treatment. Equally important is the identification of patients with good prognostic signs among patients receiving surgical intervention for TBI. We conducted a retrospective chart review of 181 patients requiring craniectomies and craniotomies for decompression or evacuation of an intracranial hemorrhage following TBI at a single level I trauma center between 2008-2010. Demographic features and perioperative clinical characteristics of these patients were examined in relation to favorable outcomes, defined as discharge to home or a rehabilitation facility, and unfavorable outcomes, defined as in-hospital mortality or discharge to step-down medical facilities. Younger age, greater Glasgow Coma Scale (GCS) score on admission, absence of preoperative coagulopathies, absence of hypernatremia, and absence of fever were all independent predictors of favorable outcome. Additionally, increased operative duration and increased length of hospital stay were identified as independent predictors of negative outcomes after surgery. This work supports some of the current prognostic models in the literature and identifies additional clinical variables with predictive value of early outcome and discharge status in patients undergoing surgical evacuation of traumatic intracranial hemorrhages.     

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。     

Problem alcohol use in veterans with mild traumatic brain injury: Associations with cognitive performance and psychiatric symptoms

Introduction: Given that little is known about the associations between alcohol use, cognition, and psychiatric symptoms among veterans with a history of mild traumatic brain injury (mTBI), we aimed to (a) characterize how they differ from veteran controls on a measure of problem drinking; (b) investigate whether problem drinking is associated with demographic or mTBI characteristics; and (c) examine the associations between alcohol use, mTBI history, psychiatric functioning, and cognition. Method: We assessed 59 veterans (n = 32 with mTBI history; n = 27 military controls) for problem alcohol use (Alcohol Use Disorders Identification Test: AUDIT), psychiatric symptoms, and neuropsychological functioning. Results: Compared to controls, veterans with mTBI history were more likely to score above the AUDIT cutoff score of 8 (p = .016), suggesting a higher rate of problem drinking. Participants with mTBI history also showed elevated psychiatric symptoms (ps < .001) and lower cognitive scores (ps < .05 to < .001). Veterans with higher AUDIT scores were younger (p = .05) and had less education (p < .01) and more psychiatric symptoms (ps < .01), but mTBI characteristics did not differ. After controlling for combat and mTBI history (R² = .04, ns) and posttraumatic stress disorder (PTSD) symptoms (ΔR² = .08, p = .05), we found that higher AUDIT scores were associated with poorer attention/processing speed, F(9, 37) = 2.55, p = .022; ΔR² = .26, p = .03. Conclusions: This preliminary study suggested that veterans with mTBI history may be at increased risk for problem drinking. Problem alcohol use was primarily associated with more severe PTSD symptoms and poorer attention/processing speed, though not with combat or mTBI characteristics per se. Importantly, findings emphasize the importance of assessing for and treating problematic alcohol use and comorbid psychiatric symptoms among veterans, including those with a history of neurotrauma.