大鼠弥漫性脑损伤后血浆中一氧化氮及内皮素含量的变化

一、材料及方法Ｗｉｓｔａｒ大鼠 30只 ,随机分为 3组 ,每组 10只。其中一组为对照组 ,另二组按照Ｍａｒｍａｒｏｕ等人建立的模型分别造成轻度及重度弥漫性脑损伤。伤后六小时取大鼠右心室血 5ｍｌ,离心 10分钟。提取血浆后置于 - 80℃冰箱中保存待检。依照南京建成生物工程研究所提供的试剂盒测量血浆ＮＯ浓度。采用北京东亚免疫技术研究所提供的ＥＴ测量放免药盒 ,测量血浆ＥＴ浓度。数据以 ｘ±ｓ表示 ,所有数据以ＡＮＯ ＶＡ、Ｄｕｎｃａｎ法分析检验。α水准定为Ｐ <0 0 5。二、结果轻、重度弥漫性脑损伤后血浆中ＮＯ及ＥＴ 1均有明…     

脑损伤大鼠血浆及海马血管活性肠肽含量变化和意义

通过RIA法检测脑损伤大鼠血浆及海马匀浆中VIP含量变化,探讨VIP对海马神经原坏死的影响。结果:脑损伤后VIP含量变化与病程有关,伤后30min海马、24h血浆、海马含量明显低于对照组,而伤后6h、72h血浆及海马含量明显高于对照组.血浆、海马VIP间存在显著相关性。结论:VIP是引起脑损伤后海马缺血再灌注及神经原坏死的重要因素。     

急性脑血管病患者血浆肿瘤坏死因子—α含量的动态变化及？…

目的 动态观察急性脑血管病患者血浆肿瘤坏死因子－α水平的变化,探讨其临床意义。方法 采用双抗体夹心（ＥＬＩＳＡ）法测定了７４例急性脑血管病（ＡＣＶＤ）患者及４２例正常对照者血浆肿瘤坏死因子－α（ＴＮＦ－α）水平。     

肿瘤坏死因子α和缺血性脑损伤

缺血性脑损伤是由多种因素综合作用的结果,肿瘤坏死因子α是一种参与缺血性脑损伤病理生理过程的多功能细胞因子,具有双重、多样及网络性生物效应,在脑缺血的不同阶段产生不同甚至相反的综合性作用。本文对近年来脑缺血时肿瘤坏死因子α的表达变化、作用及相关机制的研究进展进行了综述。文中表明肿瘤坏死因子α在脑缺血后反应性增高,不仅可促进炎性坏死和细胞凋亡,而且还具有一定的神经保护作用。通过进一步研究其双向作用的机制,阻断它的神经毒性作用,充分发挥其神经保护作用,可为脑缺血损伤的有效治疗提供新思路。     

肿瘤坏死因子-α在大鼠实验性脑出血脑损伤中的作用

目的 探讨肿瘤坏死因子-α（TNF-α）在大鼠实验性脑出血（ICH）后脑损伤中的作用。方法 采用立体定向自体血注入大鼠尾状核建立ICH模型。观察ICH大鼠术前及术后各时点血肿周围脑组织的TNF-α水平、含水量变化及神经功能障碍评分,并与对照组比较。对TNF-α水平与脑含水量、神经功能障碍评分进行相关分析。结果 ICH组术后12～96hTNF-α水平明显高于对照组（均P〈0．05）。ICH组术后各时点神经功能障碍评分与相应时点脑组织TNF-α水平呈负相关（r=-0．678,P〈0．001）,脑含水量与TNF-α水平呈正相关（r=0．541,P〈0．05）。结论 大鼠ICH后腑组织TNF-α水平明显增加,加重脑损伤和脑水肿。     

肿瘤坏死因子与脑出血后继发性脑损伤

脑出血（intracerebral hemorrhage,ICH）是临床上多发病、常见病之一,其临床治疗效果仍不理想,死亡率和致残率均很高。目前认为,ICH后除血肿本身的占位和压迫效应外,血肿周围神经细胞的凋亡、血脑屏障的破坏、脑水肿、局部脑血流量下降以及炎症反应等是导致ICH后继发性脑损伤的重要因素。     

大鼠脑出血后血浆内皮素含量变化实验研究

目的探讨在脑出血的病理过程中大量释放具有生物活性的血管活性肽-内皮素与脑出血之间的关系,及其对脑出血周围脑组织缺血损害的病理学意义。方法实验动物为Wistar大鼠,随机分为两组脑出血组24只,用大鼠自体静脉血制造脑出血模型;对照组23只。分别于脑出血后4h,8h,12h,24h,72h,及7d取血,进行选定指标的外周血测定。按照上述时间对于不同实验组动物的外周血进行血清内皮素测定。取8h的血清测定值,两组测定值比较。所有数据均以均值±标准差表示,应用专用统计学软件进行t检验。结果在脑出血的6个时间中,4项实验指标均呈现渐升渐降的变化特征,且都在8h血样中达到高峰值,两组相比有统计学意义。结论血浆内皮素在脑出血的早期8h呈现高峰值,提示我们脑出血后脑内ET过度表达可能是血肿周围存在水肿和继发缺血的主要因素之一。ET也可以作为估计预后的一种指标广泛应用于临床。     

多发核心家系精神分裂症血浆肿瘤坏死因子α的研究

目的 检测肿瘤坏死因子-α(TNF-α)血浆浓度变化,探讨TNF-α与精神分裂症的关系。方法 将同胞中有2名及2名以上符合ICD-10精神分裂症诊断标准的患者的51个家系的222人纳入研究,其中父母组94人,患病同胞组98人,非患病同胞组30人,同时纳入非血亲正常对照组40人。用酶联免疫吸附法(ELISA)对TNF-α血浆浓度进行测定,比较各组血浆浓度变化。结果 (1)4组间血浆TNF-α浓度(pg/ml)比较差异存在显著性(F=4.595,P=0.004),患病同胞组血浆TNF-α浓度(62.01±35.01)分别低于非患病同胞组(92.02±43.78)、非血亲正常对照组(82.94±41.62)及父母组(77.23±35.05),差异均有显著性(P=0.001,P=0.01,P=0.016)。(2)在病人组中,按是否服药(服药组:69.11±37.29;未服药组:67.01±36.36)、性别(男:71.64±40.70;女:65.06±32.99)分别分组比较中,差异均无显著性(P>0.05);年龄与血浆TNF-α浓度之间无明显相关性(r=0.037,P=0.717),病程长短与血浆TNF-α浓度之间也无明显相关性(r=0.104,P=0.306)。结论 精神分裂症患者血浆TNF-α浓度低于正常,年龄、病程、抗精神病药物、性别对精神分裂症血浆TNF-α浓度没有明显影响,提示精神分裂症患者免疫功能降低,支持免疫功能异常假说。     

肿瘤坏死因子α多克隆抗体对新生大鼠缺氧缺血性脑损伤的保护作用研究

目的研究肿瘤坏死因子（ＴＮＦ）α多克隆抗体对新生大鼠缺氧缺血性脑损伤（ＨＩＢＤ）后大脑的保护效应。方法制备左脑ＨＩＢＤ的新生大鼠模型,于ＨＩＢＤ前后分别腹腔注射一定浓度的ＴＮＦα多克隆抗体,观察用药前后损伤大脑脑水含量及组织病理学变化。结果ＨＩＢＤ前后腹腔注射ＴＮＦα多克隆抗体可明显降低脑水含量（Ｐ＜０．０１）,大脑水肿明显减轻,神经元死亡明显减少,但对其相应ｍＲＮＡ转录无影响。结论ＴＮＦα多克隆抗体可以拮抗ＴＮＦα的炎性作用,对ＨＩＢＤ后的大脑有保护效应     

脑瘤病人血浆内皮素-1含量的初步研究

目的:本文通过测定分析常见几种脑瘤病人血浆ET—1含量,初步探讨脑瘤病人血浆ET—1含量变化的临床意义。方法:采用均相竞争放射免疫方法直接测定37例脑瘤病人和24例对照组血浆ET-1含量。结果:脑瘤病人血浆ET—1含量为71.014ng/L,比对照组53.52mg/L和标准值50.8ng/L都高,有统计学意义。不同病理类型的脑瘤病人术前血浆ET-1含量有如下趋势:听神经瘤>脑膜瘤>颅咽管瘤>垂体瘤>胶质瘤。虽然脑膜瘤、胶质瘤和垂体瘤病人血浆ET-1含量比对照组均显著增高,但各病理类型之间无显著性差异。结论:脑瘤病人血浆ET-1可能参与肿瘤的发生、发展、分化过程,同时ET-1也可能调节肿瘤的血液供应。     

颅脑损伤患者血浆凝血酶敏感蛋白-1、血浆组织因子水平与迟发性颅内血肿的相关性

目的 分析颅脑损伤患者血浆凝血酶敏感蛋白-1(TSP-1)、血浆组织因子(TF)水平,探讨二者与迟发性颅内血肿的关系.方法 回顾性分析2017年8月至2019年8月本院收治的行开颅手术治疗的重型颅脑损伤患者115例,根据术后颅脑CT复查是否发生迟发性颅内血肿分为非迟发性颅内血肿组85例,迟发性颅内血肿组30例.收集比较...     

Tumor necrosis factor in traumatic brain injury: effects of genetic deletion of p55 or p75 receptor

The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects of genetic deletion of either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage and apoptosis-related cell death/survival gene expression (bcl-2/bax), and microglia/macrophage (M/M) activation in wild-type (WT) and knockout mice after TBI. Injured p55 (−/−) mice showed a significant attenuation while p75 (−/−) mice showed a significant worsening of sensorimotor deficits compared with WT mice over 4 weeks postinjury. At the same time point, contusion volume in p55 (−/−) mice (11.1±3.3 mm³) was significantly reduced compared with WT (19.7±3.4 mm³) and p75 (−/−) mice (20.9±3.2 mm³). At 4 hours postinjury, bcl-2/bax ratio mRNA expression was increased in p55 (−/−) compared with p75 (−/−) mice and was associated with reduced DNA damage terminal deoxynucleotidyl transferaseYmediated dUTP nick end labeling (TUNEL-positivity), reduced CD11b expression and increased Ym1 expression at 24 hours postinjury in p55 (−/−) compared with p75 (−/−) mice, indicative of a protective M/M response. These data suggest that TNF may exacerbate neurobehavioral deficits and tissue damage via p55 TNF receptor whose inhibition may represent a specific therapeutic target after TBI.     

Tumor necrosis factor alpha and Fas receptor contribute to cognitive deficits independent of cell death after concussive traumatic brain injury in mice

Tumor necrosis factor alpha (TNFα) and Fas receptor contribute to cell death and cognitive dysfunction after focal traumatic brain injury (TBI). We examined the role of TNFα/Fas in postinjury functional outcome independent of cell death in a novel closed head injury (CHI) model produced with weight drop and free rotational head movement in the anterior–posterior plane. The CHI produced no cerebral edema or blood–brain barrier damage at 24 to 48 hours, no detectable cell death, occasional axonal injury (24 hours), and no brain atrophy or hippocampal cell loss (day 60). Microglia and astrocytes were activated (48 to 72 hours). Tumor necrosis factor-α mRNA, Fas mRNA, and TNFα protein were increased in the brain at 3 to 6 hours after injury (P<0.001 versus sham injured). In wild-type (WT) mice, CHI produced hidden platform (P=0.009) and probe deficits (P=0.001) in the Morris water maze versus sham. Surprisingly, injured TNFα/Fas knockout (KO) mice performed worse in hidden platform trials (P=0.036) but better in probe trials than did WT mice (P=0.0001). Administration of recombinant TNFα to injured TNFα/Fas KO mice reduced probe trial performance to that of WT. Thus, TNFα/Fas influence cognitive deficits independent of cell death after CHI. Therapies targeting TNFα/Fas together may be inappropriate for patients with concussive TBI.     

Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from Parkinsonian brain

Summary. The activities of caspase-1 and caspase-3 were measured by use of fluoropeptides as substrates for the first time in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients. The activities of caspases in the brain were significantly higher in the substantia nigra from parkinsonian patients than those in the brain from control patients (p < 0.01). However, the activities of caspases in the caudate nucleus, putamen, cerebellum, and frontal cortex showed no significant difference between parkinsonian and control patients. The tumor necrosis factor (TNF) receptor R1 (TNF-R1, p55) level was also elevated in the substantia nigra of the parkinsonian brain in comparison with that of controls (p < 0.05). Since both caspases and TNF-R1 may play important roles in apoptotic cell death through TNF-α-induced signaling pathway, our present data suggest the presence of a proapoptotic environment in the substantia nigra of parkinsonian brain, probably inducing vulnerability of neurons and glias towards a variety of noxious factors. Received May 17, 1999; accepted November 15, 1999     

Tumor necrosis factor enhancement of transient outward potassium currents in cultured rat cortical neurons

The effect of recombinant human tumor necrosis factor-α (TNF) on voltage-gated membrane currents of cultured neurons derived from embryonic rat cerebral cortex was studied using the whole-cell patch-clamp technique. Treatment of neurons with TNF resulted in an increase in outward potassium current density, dependent upon the concentration of TNF and the incubation time, without affecting other membrane currents such as barium and N-methyl-D-aspartate (NMDA). Long exposures (12–48 hr) to TNF (10–100 ng/ml) increased transient outward potassium current (A-current) density without affecting the parameters of activation and inactivation of the current. Prolonged exposures to TNF diminished its increasing effect on the A-current. Since the increase of A-current density induced by TNF is inhibited by both the anti-TNF receptor antibody and cycloheximide treatment, the effect of TNF might be mediated through receptors and by de novo synthesis of the channel protein itself and/or modulating proteins associated with the channel activities. Results indicate that phosphatidylcholine-specific phospholipase C and protein kinase C, but not ceramide, are involved in the signal transduction. In toxicological experiments, TNF had no neurotoxicity. Moreover, a 12 hr pretreatment of TNF protected neurons against NMDA-induced neurotoxicity. This protective effect of TNF was canceled by 4-aminopyridine, an A-current blocker, suggesting that the increase of A-current densities induced by TNF contributes to the neuroprotection. J. Neurosci. Res. 50:990–999, 1997. © 1997 Wiley-Liss, Inc.     

NPS 1506 attenuates cognitive dysfunction and hippocampal neuron death following brain trauma in the rat

Although several noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to be substantially efficacious in experimental models of brain trauma, side effects associated with this class of compounds have impeded clinical application. Therefore, new noncompetitive NMDA receptor antagonists have been developed, including NPS 1506, that appear to be nontoxic but retain efficacy. In the present study, we evaluated the efficacy of NPS 1506 in a model of parasagittal fluid percussion brain trauma in the anesthetized rat. Administration of 1 mg/kg NPS 1506 at both 10 min and 4 h posttrauma induced no changes in brain temperature, mean arterial pressure, pulse, or arterial blood gasses. At 1 week postinjury, animals treated with the same dosing regimen of NPS 1506 demonstrated a dramatic attenuation of memory dysfunction evaluated by a water maze task (P < 0.02) and had greatly reduced neuron death in the CA3 subfield of the hippocampus (P < 0.01). However, NPS 1506 treatment did not significantly affect the extent of cortical tissue loss following injury. Since memory dysfunction and hippocampal damage are common and potentially related consequences of brain trauma in humans, our results suggest that NPS 1506 treatment may have clinical utility.     

多发性硬化和格林-巴利综合征患者体液中TNF及IL-1水平与临床关系的研究

测定了多发性硬化(MS)和格林-巴利综合征(GBS)患者的细胞因子，发现活动的MS血清和脑脊液(CSF)TNF水平显著高于稳定的MS和对照组。GBS患者急性期CSF和血清TNF水平显著高于对照组及治疗后水平。另外，MS和GBS患者CSF的TNF水平均高于相应的血清水平。通过研究还发现MS和GBS组CSF的蛋白含量显著增高。此外，MS组CSF白细胞敷与CSF的TNF水平及CSF蛋白含量相关，且CSF蛋白含量与血清、CSF的TNF水平相关。这表明TNF一方面可能来源干鞘内的单个核细胞，另一方面由于血脑屏障受损可能来源于血液，另外还可能来源于神经肢质细胞及血管内皮细胞。TNF可能在炎性脱鞘病发病初期起作用。     

Increased levels of soluble tumor necrosis factor receptor in patients with multiple sclerosis and HTLV-1-associated myelopathy

Tumor necrosis factor-α (TNF-α) is a potent mediator produced by activated T lymphocytes and macrophages, which may play a role in the pathogenesis and development of multiple sclerosis (MS) and HTLV-1-associated myelopathy (HAM). The first step in the induction of many biological effects elicited by TNF-α is its binding to specific cell surface receptors. A soluble form of TNF receptors (sTNF-R) can be detected in the body fluid. We measured sTNF-R levels in the sera and cerebrospinal fluid (CSF) of patients with either MS or HAM, and evaluated the correlation between this mediator and diseaseaactivity. The levels of sTNF-R in the sera and CSF of patients with MS were significantly increased compared with controls, particularly patients with acute relapsing MS during an exacerbation (P < 0.001). CSF levels of sTNF-R showed a strong correlation with those of TNF (r = 0.716, P < 0.001). Higher levels of sTNF-R in the sera of HAM patients were detected as compared with those of either controls (P < 0.001) or non-HAM carriers (P < 0.001). Patients with HAM exhibited significantly higher CSF levels of sTNF-R than those with other neurological diseases (P < 0.0001). These results suggest that the detection of sTNF-R in the sera and CSF may predict disease progression. Availability of such a marker wou ld be useful in monitoring disease activity.