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1.
Traumatic brain injury affects over a million Americans annually, but pharmacological therapy remains limited. Current standards of care in acute, subacute and chronic phases of injury are primarily supportive. This review discusses pharmacological strategies and future directions in patient treatment emphasizing pleiotropic agents targeting inflammation, oxidative damage, and glutamate excitotoxicity. 相似文献
2.
The fact that traumatic brain injury is the leading cause of death and disability in the most active population (< 45 years of age) of industrialised countries underscores the need for intensified efforts to define and implement effective neuroprotective strategies. However, despite progressively growing knowledge on the mechanisms involved in the pathobiology of traumatic brain injury and promising preclinical findings, most of the neuroprotection trials have failed to deliver the expected level of beneficial effects. Some of the possible reasons underlying the lack of success of these clinical trials are addressed in this review, which describes some of the most promising and/or controversial ongoing clinical trials from their pathophysiological basis. In addition, new neurobiological findings and their consequence for novel neuroprotective approaches are discussed. 相似文献
3.
The fact that traumatic brain injury is the leading cause of death and disability in the most active population (< 45 years of age) of industrialised countries underscores the need for intensified efforts to define and implement effective neuroprotective strategies. However, despite progressively growing knowledge on the mechanisms involved in the pathobiology of traumatic brain injury and promising preclinical findings, most of the neuroprotection trials have failed to deliver the expected level of beneficial effects. Some of the possible reasons underlying the lack of success of these clinical trials are addressed in this review, which describes some of the most promising and/or controversial ongoing clinical trials from their pathophysiological basis. In addition, new neurobiological findings and their consequence for novel neuroprotective approaches are discussed. 相似文献
4.
Traumatic brain injury (TBI) affects 1.6 million Americans annually. The injury severity impacts the overall outcome and likelihood for survival. Current treatment of acute TBI includes surgical intervention and supportive care therapies. Treatment of elevated intracranial pressure and optimizing cerebral perfusion are cornerstones of current therapy. These approaches do not directly address the secondary neurological sequelae that lead to continued brain injury after TBI. Depending on injury severity, a complex cascade of processes are activated and generate continued endogenous changes affecting cellular systems and overall outcome from the initial insult to the brain. Homeostatic cellular processes governing calcium influx, mitochondrial function, membrane stability, redox balance, blood flow and cytoskeletal structure often become dysfunctional after TBI. Interruption of this cascade has been the target of numerous pharmacotherapeutic agents investigated over the last two decades. Many agents such as selfotel, pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol were ineffective in clinical trials. While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending. Consequently, no neuroprotective treatment options currently exist that improve neurological outcome after TBI. Investigations to date have extended understanding of the injury mechanisms and sites for intervention. Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials. 相似文献
5.
Traumatic brain injury (TBI) is a devastating disease, predominately affecting young people. Although the prognosis for TBI victims has improved in recent years, many survivors of TBI suffer from emotional, cognitive and motor disturbances and a decreased quality of life. In recent years, there has been a rapid increase in the number of pharmacological targets evaluated in clinically-relevant experimental TBI models, showing improved cognitive and motor outcome and decreased loss of brain tissue. Despite the completion of several recent clinical trials using compounds showing neuroprotection in preclinical studies, pharmaceutical treatment strategies with proven clinical benefit are still lacking. This paper reviews the preclinical pharmacological treatment studies evaluated to date in experimental models of TBI. Although human TBI is a complex and multifaceted disease, these studies provide encouraging translational data suggesting that pharmacological compounds, delivered in a clinically-relevant time window, may improve the outcome of TBI patients. 相似文献
6.
Introduction: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. To date, there are no pharmacologic agents proven to improve outcomes from TBI because all the Phase III clinical trials in TBI have failed. Thus, there is a compelling need to develop treatments for TBI. Areas covered: The following article provides an overview of select cell-based and pharmacological therapies under early development for the treatment of TBI. These therapies seek to enhance cognitive and neurological functional recovery through neuroprotective and neurorestorative strategies. Expert opinion: TBI elicits both complex degenerative and regenerative tissue responses in the brain. TBI can lead to cognitive, behavioral, and motor deficits. Although numerous promising neuroprotective treatment options have emerged from preclinical studies that mainly target the lesion, translation of preclinical effective neuroprotective drugs to clinical trials has proven challenging. Accumulating evidence indicates that the mammalian brain has a significant, albeit limited, capacity for both structural and functional plasticity, as well as regeneration essential for spontaneous functional recovery after injury. A new therapeutic approach is to stimulate neurovascular remodeling by enhancing angiogenesis, neurogenesis, oligodendrogenesis, and axonal sprouting, which in concert, may improve neurological functional recovery after TBI. 相似文献
7.
The management of traumatic brain injury (TBI) is challenging and there is a need for neuroprotective therapies. A better understanding of the pathomechanism of TBI, particularly of the evolution of secondary damage, is providing targets for new approaches and selected ones in clinical development are described. Clinical trials that have been discontinued in the past for lack of efficacy or other reasons are also listed. One of the problems has been the translation of promising animal experimental results into clinically successful therapies. The complexity of sequelae of TBI requires a multifaceted approach. In addition to the investigation of drugs for neuroprotective effect in TBI, new technologies based on cell/gene therapies, biomarkers and nanobiotechnology are being employed for the integration of neuroprotection with neuroregeneration and are promising. 相似文献
8.
Traumatic brain injury (TBI) represents the leading cause of death in young individuals. It triggers the accumulation of harmful mediators, leading to secondary damage, yet protective mechanisms are also set in motion. The endocannabinoid (eCB) system consists of ligands, such as anandamide and 2-arachidonoyl-glycerol (2-AG), receptors (e.g. CB1, CB2), transporters and enzymes, which are responsible for the 'on-demand' synthesis and degradation of these lipid mediators. There is a large body of evidence showing that eCB are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain's compensatory or repair mechanisms. These are mediated via CB receptors signalling pathways that are linked to neuronal survival and repair. The levels of 2-AG, the most highly abundant eCB, are significantly elevated after TBI and when administered to TBI mice, 2-AG decreases brain oedema, inflammation and infarct volume and improves clinical recovery. The role of CB1 in mediating these effects was demonstrated using selective antagonists or CB1 knockout mice. CB2 were shown in other models of brain insults to reduce white blood cell rolling and adhesion, to reduce infarct size and to improve motor function. This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies with special emphasis on TBI. 相似文献
10.
目的探讨颅脑损伤保守治疗期间的观察与护理原则。方法选取本院2009年8月~2011年4月30例颅脑外伤暂行保守治疗患者的临床资料,记为观察组,选取2006年7月~2009年5月收治的30例颅脑外伤行保守治疗患者的临床资料作为对照组。对照组患者采用常规护理,治疗组患者采用系统性护理干预,应用焦虑自评量表(SAS)对两组患者进行心理评估,比较两组患者心理状况、死亡率、转手术率及护理满意度。结果观察组患者SAS评分为(51.4±8.6)分,低于对照组,观察组护理满意度为93.3%,高于对照组,两组比较差异有统计学意义(P〈0.05)。观察组患者转手术率为6.7%,低于对照组的26.7%,两组比较差异有统计学意义(P〈0.05)。结论对颅脑外伤保守治疗患者进行系统性护理干预,能降低患者死亡率及转手术率,提高护理满意度,值得在临床推广。 相似文献
11.
Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentrated on prevention of the production of reactive oxygen species or free radicals (xanthine-oxidase-, nitric oxide synthase-, and prostaglandin inhibition), anti-inflammatory effects (erythropoietin, melatonin, Xenon) and anti-apoptotic interventions (nuclear factor kappa B- and c-jun N-terminal kinase inhibition); in a later stage stimulation of neurotrophic properties in the neonatal brain (erythropoietin, growth factors) can be targeted to promote neuronal and oligodendrocyte regeneration. Combination of pharmacological means of treatment with moderate hypothermia, which is accepted now as a meaningful therapy, is probably the next step in clinical treatment to fight post-asphyxial brain damage. Further studies should be directed at a more rational use of therapies by determining the optimal time and dose to inhibit the different potentially destructive molecular pathways or to enhance endogenous repair while at the same time avoiding adverse effects of the drugs used. 相似文献
12.
In industrialised countries, the mean per capita incidence of traumatic brain injury (TBI) that results in a hospital presentation is 250 per 100,000. In Europe and North America alone, this translates to > 2 million TBI presentations annually. Approximately 25% of these presentations are admitted for hospitalisation. Despite the significance of these figures, there is no single interventional pharmacotherapy that has shown efficacy in the treatment of clinical TBI. This lack of efficacy in clinical trials may be due, in part, to the inherent heterogeneity of the traumatic brain injury population. However, it is the multifactorial nature of secondary injury that also poses a major hurdle, particularly for those therapies that have been designed to specifically target an individual injury factor. It is now becoming increasingly recognised that any successful TBI therapy may have to simultaneously affect multiple injury factors, somewhat analogous to other broad spectrum interventions. Recent efforts in experimental TBI have therefore focussed on developing novel pharmacotherapies that may affect multiple injury factors and thus improve the likelihood of a successful outcome. While a number of interventions are noteworthy in this regard, this review will focus on three novel compounds that show particular promise: magnesium, substance P antagonists and cyclosporin A. 相似文献
13.
In industrialised countries, the mean per capita incidence of traumatic brain injury (TBI) that results in a hospital presentation is 250 per 100,000. In Europe and North America alone, this translates to > 2 million TBI presentations annually. Approximately 25% of these presentations are admitted for hospitalisation. Despite the significance of these figures, there is no single interventional pharmacotherapy that has shown efficacy in the treatment of clinical TBI. This lack of efficacy in clinical trials may be due, in part, to the inherent heterogeneity of the traumatic brain injury population. However, it is the multifactorial nature of secondary injury that also poses a major hurdle, particularly for those therapies that have been designed to specifically target an individual injury factor. It is now becoming increasingly recognised that any successful TBI therapy may have to simultaneously affect multiple injury factors, somewhat analogous to other broad spectrum interventions. Recent efforts in experimental TBI have therefore focussed on developing novel pharmacotherapies that may affect multiple injury factors and thus improve the likelihood of a successful outcome. While a number of interventions are noteworthy in this regard, this review will focus on three novel compounds that show particular promise: magnesium, substance P antagonists and cyclosporin A. 相似文献
15.
The role of neuroprotection in traumatic brain injury (TBI) is reviewed. Basic research and experimental investigations have identified many different compounds with potential neuroprotective effect. However, none of the Phase III trials performed in TBI have been successful in convincingly demonstrating efficacy in the overall population. A common misconception is that consequently these agents are ineffective. The negative results as reported in the overall population may in part be caused by specific aspects of the head injury population as well as by aspects of clinical trial design and analysis. The heterogeneity of the TBI population causes specific problems, such as a risk of imbalances between placebo and treated groups but also causes problems when a possible treatment effect is evaluated in relation to the prognostic effect present. Trials of neuroprotective agents should be targeted first of all to a population in which the mechanism at which the agent is directed is likely to be present and secondly to a population in which the chances of demonstrating efficacy are realistic, e.g., to patients with an intermediate prognosis. The possibilities for concomitant or sequential administration of different neuroprotective agents at different times deserve consideration. The potential for neuroprotection in TBI remains high and we should not be discouraged by recent failures obtained up until now. Rather, prior to initiating new trials, careful consideration of experimental evidence is required in order to optimise chances for mechanistic targeting and lessons learned from previous experience need to be taken to heart in the design of future studies. 相似文献
16.
The role of neuroprotection in traumatic brain injury (TBI) is reviewed. Basic research and experimental investigations have identified many different compounds with potential neuroprotective effect. However, none of the Phase III trials performed in TBI have been successful in convincingly demonstrating efficacy in the overall population. A common misconception is that consequently these agents are ineffective. The negative results as reported in the overall population may in part be caused by specific aspects of the head injury population as well as by aspects of clinical trial design and analysis. The heterogeneity of the TBI population causes specific problems, such as a risk of imbalances between placebo and treated groups but also causes problems when a possible treatment effect is evaluated in relation to the prognostic effect present. Trials of neuroprotective agents should be targeted first of all to a population in which the mechanism at which the agent is directed is likely to be present and secondly to a population in which the chances of demonstrating efficacy are realistic, e.g., to patients with an intermediate prognosis. The possibilities for concomitant or sequential administration of different neuroprotective agents at different times deserve consideration. The potential for neuroprotection in TBI remains high and we should not be discouraged by recent failures obtained up until now. Rather, prior to initiating new trials, careful consideration of experimental evidence is required in order to optimise chances for mechanistic targeting and lessons learned from previous experience need to be taken to heart in the design of future studies. 相似文献
17.
目的对比不同护理手段对外伤性重型颅脑损伤患者急救阶段的护理效果。方法将我院收治的126例外伤性重型颅脑损伤患者依据急救阶段护理方式差异分组,对比两组护理效果。结果观察组入院抢救时间与抢救费用、并发症率与死亡率均远低于对照组(P0.05);观察组病情稳定率远高于对照组(P0.05);观察组护理态度、护理技术、心理护理与健康教育满意率均较对照组更理想(P0.05)。结论临床予以外伤性重型颅脑损伤患者急救阶段临床护理路径,可有效降低抢救时间、费用与并发症率,同时对患者的病情稳定与生存率均具明显提升作用,该法深受临床欢迎,值得推广。 相似文献
18.
Head injury is a common disabling condition but regrettably facilities for rehabilitation are sparse. There is now increasing evidence of the efficacy of a comprehensive multidisciplinary rehabilitation team compared to natural recovery following brain injury. This chapter outlines some basic concepts of rehabilitation and emphasises the importance of valid and reliable outcome measures. The evidence of the efficacy of a rehabilitation programme is discussed in some detail. A number of specific rehabilitation problems are outlined including the management of spasticity, nutrition, pressure sores and urinary continence. The increasingly important role of assistive technology is illustrated, particularly in terms of communication aids and environmental control equipment. However, the major long-term difficulties after head injury focus around the cognitive, intellectual, behavioural and emotional problems. The complex management of these disorders is briefly addressed and the evidence of the efficacy of some techniques discussed. The importance of recognition of the vegetative stage and avoidance of misdiagnosis is emphasised. Finally, the important, but often neglected, area of employment rehabilitation is covered. 相似文献
19.
The intensity of experimental and clinical research to identify a neuroprotective drug for the treatment of traumatic brain injury is motivated by the devastating morbidity and mortality of this condition. Encouraging experimental work has led so far to disappointing clinical trials and the identification of new potential therapeutic targets is critically dependent on a better understanding of the chronic pathophysiology triggered by the initial insult. Future advances in the pharmacological treatment of traumatic brain injury are likely to include the evaluation of sequentially timed therapies combining multiple and targeted agents, and manipulation of the newly discovered neurogenic potential of the adult brain together with the refinement of traditional interventions to block specific cytotoxic cascades. 相似文献
20.
目的探讨老年人颅脑外伤后缺血性脑卒中发作特点及个性化治疗方案。方法针对7例颅脑外伤后急性期出现缺血性脑血管病症状的老年患者,通过脑血管造影检查分析其发病原因并根据不同的脑血管特点决定治疗方案。结果大多数患者(6/7)受伤前已存在不同程度的颅内外血管狭窄、血管壁溃疡以及附壁血栓形成等改变,提示脑缺血发作主要与这些病变为基础的脑血流下降、血栓脱落等因素密切相关。而外伤后脑灌注降低、脑血管痉挛是脑缺血发作的诱发因素。结论老年人外伤后的缺血性脑卒中发作主要与原有的脑血管基础疾病有关,预防和治疗老年人外伤后缺血性脑卒中发作,应基于这些病变特征并选择个体化治疗方案。 相似文献
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