Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: a potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO)

Erythropoietin (EPO) has recently been shown to have a neuroprotective effect in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. We, therefore, tried to analyze how recombinant human erythropoietin (rhEPO) might effect the inflammation-related factors common to TBI: nuclear factor kappa B (NF-kappaB), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in a rat TBI model. Male rats were given 0 or 5000 units/kg injections of rhEPO 1h post-injury and on days 1, 2 and 3 after surgery. Brain samples were extracted at 3 days after trauma. We measured NF-kappaB by electrophoretic mobility shift assay (EMSA); IL-1beta, TNF-alpha and IL-6 by enzyme-linked immunosorbent assay (ELISA); ICAM-1 by immunohistochemistry; brain edema by wet/dry method; blood-brain barrier (BBB) permeability by Evans blue extravasation and cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. We found that NF-kappaB, pro-inflammatory cytokines and ICAM-1 were increased in all injured animals. In animals given rhEPO post-TBI, NF-kappaB, IL-1beta, TNF-alpha and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after rhEPO treatment. Administration of rhEPO reduced brain edema, BBB permeability and apoptotic cells in the injured brain. In conclusion, post-TBI rhEPO administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which rhEPO improves outcome following TBI.     

Biomechanics of Traumatic Brain Injury: Influences of the Morphologic Heterogeneities of the Cerebral Cortex

Traumatic brain injury (TBI) can be caused by accidents and often leads to permanent health issues or even death. Brain injury criteria are used for assessing the probability of TBI, if a certain mechanical load is applied. The currently used injury criteria in the automotive industry are based on global head kinematics. New methods, based on finite element modeling, use brain injury criteria at lower scale levels, e.g., tissue-based injury criteria. However, most current computational head models lack the anatomical details of the cerebrum. To investigate the influence of the morphologic heterogeneities of the cerebral cortex, a numerical model of a representative part of the cerebral cortex with a detailed geometry has been developed. Several different geometries containing gyri and sulci have been developed for this model. Also, a homogeneous geometry has been made to analyze the relative importance of the heterogeneities. The loading conditions are based on a computational head model simulation. The results of this model indicate that the heterogeneities have an influence on the equivalent stress. The maximum equivalent stress in the heterogeneous models is increased by a factor of about 1.3–1.9 with respect to the homogeneous model, whereas the mean equivalent stress is increased by at most 10%. This implies that tissue-based injury criteria may not be accurately applied to most computational head models used nowadays, which do not account for sulci and gyri.     

脑脊液ET-1，NO浓度变化与重型颅脑外伤后脑血管痉挛的临床研究

目的研究重型颅脑外伤后脑脊液中内皮素(ET-1)、一氧化氮(NO)浓度动态变化与脑血管痉挛的关系。方法重型脑外伤病人30例。入院后24h及3、5、7d进行双侧大脑中动脉、颈内动脉颅外段脑血流速度动态检测及脑脊液ET-1、NO浓度测定。结果13例(43%)发生脑血管痉挛。伤后痉挛组与非痉挛组病人脑脊液中ET-1浓度均高于正常组,NO浓度均低于正常组。痉挛组病人ET-1及NO浓度变化过程同痉挛组的TCD表现相符,ET-1、NO浓度各组之间存在明显差异。结论颅脑外伤后脑血管痉挛发生率高,是颅脑外伤后基本病理过程之一;伤后脑血管痉挛发生的机制可能与脑脊液ET升高,NO抑制,导致血管收缩舒张平衡破坏有关。     

Medial Collagen Organization in Human Arteries of the Heart and Brain by Polarized Light Microscopy

The mechanical properties of collagen as a biopolymer ensures that collagen has a significant influence on the mechanical behavior of the host tissue. Structural organization is a key to that influence. We have assessed this relationship quantitatively in the tunica media of arteries from the heart and brain, using the polarizing light microscope and Universal stage. Arteries from 22 autopsies were isolated, cannulated and fixed with 10% buffered formalin, at a distending pressure spanning normal values in vivo. We prepared the tissue for light microscopy, with paraffin embedding, sectioning at 7 μ, and staining with picrosirius red to enhance the natural birefringence of medial collagen. Individual measurements, 30 to 50 per arterial section, referenced against the central axis of the vessel segment, revealed a coherent organization, with an average orientation which was within 1 to 2° of being perfectly concentric for all artery segments. Analysis was done with Lambert projections and circular statistics. We calculated the circular standard deviation, which was 5.2° for 27 brain arteries (S.D. 1.9°) and 5.6° (S.D. 2.1°), for 5 coronary arteries sectioned at less than 15°. Our interpretation is that medial collagen can be strained even though highly aligned, revealing a mechanical property which contrasts that of type I collagen.     

Changes in Mast Cells of Vascular Plexuses of Human Cerebral Ventricles in Atherosclerosis of Precerebral Arteries

Scanty mast cells with high saturation and weak degranulation located perivascularly and in the subepithelial zone of the villi were detected in vascular plexuses of human brain. Cerebral atherosclerosis was associated with pronounced changes in their morphofunctional organization: changed shape, decreased volume and index of saturation and degranulation, predominating in the villous part of the vascular plexus of the lateral ventricle. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 584–586, November, 2005     

脑中风患者彩色多普勒超声特征研究

目的 用彩色多普勒超声观察中老年人脑中风患者颅内及颈动脉形态、结构和血流动力学改变。方法 应用2．5MHz线阵探头分别观察155例不同类型脑中风患者和80例正常人颈动脉内中膜厚度、斑块情况及颅内与颈动脉血流动力学改变情况。结果 （1）各型脑中风组颈总动脉（CCA）内中膜厚度均较对照组明显增厚,斑块有109例出现（70．3％）,而对照组仅4例（5．0％）出现斑块;（2）各型脑中风组颈内动脉时间平均流速（TAVICA）较正常组减低、阻力指数（RI）、搏动指数（PI）较正常组明显升高;（3）脑梗死组大脑中动脉时间平均流速（TAVMCA）较正常组低,脑出血组TAVMCA较正常组明显升高,混合性中风组可出现TAVMCA升高或降低两种情况。结论 中老年人各型脑中风患者颈动脉粥样硬化程度加重,斑块出现率高及斑块所引起的颈动脉狭窄,对脑中风有直接的因果关系,联合检查颅内动脉和颈动脉血流动力学改变可协助诊断不同类型脑中风,对其疗效观察,预防复发有一定的指导作用。     

早期大剂量纳洛酮在急性重型颅脑损伤中的应用观察

目的：探讨早期大剂量纳洛酮治疗重型颅脑损伤的临床疗效。方法将70例重型颅脑损伤患者随机分为两组,均给予常规治疗,在此基础上,观察组加用纳洛酮治疗。结果观察组生命体征较快恢复稳定,觉醒时间缩短,伤后3个月GOS评分。观察组显著高于对照组。结论大剂量纳洛酮可有效改善患者脑水肿与减轻中枢神经系统损害,不失为治疗脑损伤的有效药物。     

Cerebral haemorrhage in Moyamoya disease at autopsy

Summary Nineteen fatal cases of occlusion of the circle of Willis, so-called Moyamoya disease, were examined clinicopathologically.Fresh and massive cerebral haemorrhage was confirmed in 14 and cerebral infarcts of 4 of 19 patients. Among these 14 patiens, massive haemorrhage was found in the basal ganglia, thalamus and hypothalamus of 9, and in the thalamus, cerebral peduncle and midbrain of 5. Pathologically, fibrosing stenoses or occlusions involved the circle of Willis and its major branches in all cases. In 13 of 17 patients numerous collateral channels, muscular in type, paralleled the circle, bypassing the occluded natural passages. Rupture of dilated small muscular collateral arteries was demonstrated in fresh and old haemorrhagic lesions in 3 of the 14 patients. Saccular aneurysm of cerebral arteries in the subarachnoid spaces was present in two of the 19. No rupture involved the perforating arteries in the subarachnoid space.These findings strongly suggest that in patients with Moyamoya disease rupture of overgrown perforating arteries as collaterals in brain may be main cause of single or repeated cerebral haemorrhage. Stenoses or occlusions of these perforators are presumably an important factor in the occurrence of cerebral infarcts.Supported in part by the Research Grant for the Intractable Disease from the Ministry of Health and Welfare of Japan     

Telemetry of Human Cerebral Temperature

Cerebral temperature can be monitored unobtrusively on free-ranging human subjects. We describe here a pulse-modulated radio frequency transmitter that is worn behind the ear and transmits information on temperature in the ear canal. The information can be decoded by a portable monitor or recorded for later analysis. Preliminary findings suggest the equipment can be used in a variety of studies.     

Effects of lisuride hydrogen maleate on pericontusional tissue metabolism, brain edema formation, and contusion volume development after experimental traumatic brain injury in rats

After traumatic brain injury (TBI), the primary insult is followed by a cascade of secondary events which lead to enlargement of the primary lesion and are potentially amenable to therapeutic intervention. Lisuride is a dopaminergic agonist with additional serotoninergic, adrenergic, and glutamate antagonistic properties. In lack of previous data on lisuride in TBI, and based on well documented changes of dopamine metabolism after TBI, we speculated that lisuride could provide neuroprotection in the acute and post-acute stage of controlled cortical impact (CCI) injury in rats. The effect of varying dosages of lisuride on physiological parameter was investigated. Cerebral microdialysis (CMD) was employed to provide a temporal profile of lactate, pyruvate, glucose and glutamate in the pericontusional brain tissue. Additionally, brain edema formation and the development of contusion volume were assessed. In this study, no effect of treatment was seen on physiological parameters or microdialysis profiling of tissue metabolites. Whereas posttraumatic increase in brain water content and an increase in contusion volume could be observed, there was no significant effect of treatment. Taken together, our results suggest that lisuride does not provide neuroprotection in the CCI model at the acute and subacute stages. Based on the available literature, however, it might be possible that dopamine agonists such as lisuride, respectively, improve outcome in terms of cognitive function in a chronic setting.     

A Histological, Ultrastructural and Immunohistochemical Study of Superficial Temporal Arteries and Middle Meningeal Arteries in Moyamoya Disease

Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro temporal arterio synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (El). The El had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG, IgM, and C3 positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occur ed in these arteries. Acta Pathol Jpn 41: 521 530, 1991.     

Patient perceptions of participation in group-based rehabilitation in an inpatient brain injury rehabilitation setting

Objectives

The use of groups is common in healthcare. There is a paucity of research which captures patient experiences of group participation. The aims of this study were to explore the perceptions and experiences of people with traumatic brain injury (TBI) about their participation in inpatient occupational therapy rehabilitation groups.

脑外伤病人记忆功能的康复特点

脑外伤现已成为危害人们健康的主要疾病之一。脑外伤会引起多种认知功能障碍 ,如注意、记忆和语言等 ,其中记忆障碍较为常见。脑外伤后会有一段时间失去意识 ,同时伴有失定向、意识混乱 ,以及情节记忆受损等症状 ,称为创伤后遗忘 (ｐｏｓｔｔｒａｕ ｍａｔｉｃａｍｎｅｓｉａ ,ＰＴＡ) [1- 3] 。ＰＴＡ可以持续几分钟或几个月不等 ,它对于预测脑外伤后认知功能康复的程度等有重要的参考价值 ,ＰＴＡ的持续时间短 ,程度轻 ,其后认知功能的康复就会较好。对ＰＴＡ最简单的评价是询问病人在外伤后能够记起的第一件事 ,以及病人能够记起的外伤前…     

Memory and executive functions correlates of self-awareness in traumatic brain injury

Objective: The purpose of this study was to investigate the contribution of executive functions (EF) components and episodic and working memory variables, as well as clinical and demographic factors, to awareness of cognitive ability in traumatic brain injury (TBI).

Methods: Sixty-five TBI patients (mild: n?=?26; moderate/severe: n?=?39) took part in the study. Independent stepwise regression models were calculated for EF and memory predictors, with awareness being measured by patient/informant discrepancy in the Patient Competency Rating Scale.

Results: Models with EF variables indicated that semantic verbal fluency and age are the best predictors of awareness, whereas models including mnemonic functions suggested verbal delayed episodic recall and TBI severity as predictors.

Conclusions: These results are discussed in relation to clinical implications, such as the need to focus efforts of rehabilitation in the cognitive abilities related to awareness, and theoretical models.     

Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury

Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade-positive neurons in the rat hippocampus 24 h after injury but does not improve neurobehavioral outcome (spatial memory deficits) 2 weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory.     

大鼠脑缺血及再灌注情形下血液触变性的研究

本文建立了大鼠脑缺血及再灌注模型,并对缺血以及缺血后再灌注不同时间的血液触变性进行了实验研究,用Ｈｕａｎｇ’ｓ方程拟合实验曲线以得到各组血液的５个触变性参数,结果表明：缺血以及缺血后再灌注不同时间,以血液触变性参数有明显的影响。缺血过程中,τ１和μ的值随着缺血时间的增加逐渐降低,缺血再灌注１小时的τ０和μ明显大于缺血期的值,τ０也高于正常值,随着再灌注的增加,τ０逐渐回落至正常血液水平,同时μ也逐     

大鼠脑底动脉降钙素基因相关肽能神经纤维分布的形态学观察

目的　探讨 14只成年鼠和 14只老年鼠脑底主要动脉降钙素基因相关肽能神经纤维的分布特征。方法　应用免疫组织化学ABC法、神经交点计数法。结果　成年鼠脑底各主要动脉壁上均含有呈线状黑色的CGRP能免疫反应阳性神经纤维 ,分布密度以大脑前动脉最高 ,其次是大脑中动脉、大脑后动脉、基底动脉。各动脉间CGRP能神经纤维密度比较具有统计学意义 (P <0 .0 1) ,成年鼠脑底动脉壁CGRP能神经纤维以环行分布为主 ;老年鼠脑底动脉壁CGRP能神经纤维密度以大脑前动脉最高 ,走行方式以网状分布为主 ;老年鼠脑底各主要动脉壁CGRP能神经纤维分布密度低于成年鼠相应脑底动脉。结论　不同脑底动脉CGRP能神经纤维分布特征各异 ,老年鼠较成年鼠脑底动脉CGRP能神经纤维的分布密度为低     

胎儿脐静脉与大脑中动脉拉伸力学特性的对比分析

对比分析胎儿脐静脉与大脑中动脉的力学特性,为大脑中动脉损伤以胎儿脐静脉移植修复提供生物力学特性基础。取正常人新鲜尸体大脑中动脉与新鲜胎儿脐静脉各15个试样进行拉伸实验。分别将大脑中动脉和胎儿脐静脉试样装夹在电子万能试验机的夹头内,以0.3 mm/min的实验速度对试样进行实验。结果表明,胎儿脐静脉的弹性限度应变值、最大应变值大于大脑中动脉组,差异显著(P0.05),胎儿脐静脉组最大应力、弹性模量值小于大脑中动脉组,差异显著(P0.05)。胎儿脐静脉的应力-应变曲线和大脑中动脉的应力-应变曲线变化规律相似。胎儿脐静脉的拉伸力学特性有利于移植大脑中动脉损伤的修复。     

沙疗对人体弯曲股动脉血流动力学影响

目的研究沙疗对人体弯曲股动脉血流动力学的影响,从血流动力学角度进一步揭示沙疗的疗效机理。方法以人体主动脉CT图像为依据,建立弯曲股动脉三维有限元模型,并以实验所测受试者心率、股动脉血流速度峰值和内径作为初始条件和边界条件进行有限元数值模拟,对比分析在流固耦合条件下沙疗前后弯曲血管血液流场血流速度、压力和壁面切应力。结果与沙疗前相比,沙疗后血管弯曲段纵向速度有较大提高,增幅为22.76%;二次回流速度明显减弱,减少了18.26%;壁面切应力减少2.01%。结论沙疗会使血液流动性效果显著,并提高股动脉血液的流动性,预防动脉内血小板的沉积;沙疗后二次回流速度流动现象明显减弱,避免血液中物质产生沉积,临床上对预防动脉粥样硬化、血栓等各种血管疾病有积极作用。