Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature

被引:119
作者
Schouten, Joost W. [1 ]
机构
[1] Erasmus MC, Dept Neurosurg, NL-3000 CA Rotterdam, Netherlands
关键词
clinical trial; head injury; neuroprotection; neurotrauma; traumatic brain injury; SEVERE HEAD-INJURY; NITRIC-OXIDE; CEREBROSPINAL-FLUID; CLINICAL-TRIALS; MULTICENTER TRIAL; MAGNESIUM-SULFATE; PROGESTERONE; ERYTHROPOIETIN; OUTCOMES; ALLOPREGNANOLONE;
D O I
10.1097/MCC.0b013e3280895d5c
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Purpose of review Translating the efficacy of neuroprotective agents in experimental traumatic brain injury to clinical benefit has proven an extremely complex and, to date, unsuccessful undertaking. The focus of this review is on neuroprotective agents that have recently been evaluated in clinical trials and are currently under clinical evaluation, as well as on those that appear promising and are likely to undergo clinical evaluation in the near future. Recent findings Excitatory neurotransmitter blockage and magnesium have recently been evaluated in phase III clinical trials, but showed no neuroprotective efficacy. Cyclosporin A, erythropoietin, progesterone and bradykinin antagonists are currently under clinical investigation, and appear promising. Summary Traumatic brain injury is a complex disease, and development of clinically effective neuroprotective agents is a difficult task. Experimental traumatic brain injury has provided numerous promising compounds, but to date these have not been translated into successful clinical trials. Continued research efforts are required to identify and test new neuroprotective agents, to develop a better understanding of the sequential activity of pathophysiologic mechanisms, and to improve the design and analysis of clinical trials, thereby optimizing chances for showing benefit in future clinical trials.
引用
收藏
页码:134 / 142
页数:9
相关论文
共 68 条
[1]  
[Anonymous], COCHRANE DATABASE SY
[2]   A TRIAL OF THE EFFECT OF NIMODIPINE ON OUTCOME AFTER HEAD-INJURY [J].
BAILEY, I ;
BELL, A ;
GRAY, J ;
GULLAN, R ;
HEISKANAN, O ;
MARKS, PV ;
MARSH, H ;
MENDELOW, DA ;
MURRAY, G ;
OHMAN, J ;
QUAGHEBEUR, G ;
SINAR, J ;
SKENE, A ;
TEASDALE, G ;
WATERS, A .
ACTA NEUROCHIRURGICA, 1991, 110 (3-4) :97-105
[3]   Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats [J].
Bareyre, FM ;
Saatman, KE ;
Raghupathi, R ;
McIntosh, TK .
JOURNAL OF NEUROTRAUMA, 2000, 17 (11) :1029-1039
[4]  
BRAAKMAN R, 1994, J NEUROSURG, V80, P797
[5]  
*BRAIN TRAUM FDN, IN PRESS J NEUROTRAU
[6]   The chemical biology of clinically tolerated NMDA receptor antagonists [J].
Chen, Huei-Sheng Vincent ;
Lipton, Stuart A. .
JOURNAL OF NEUROCHEMISTRY, 2006, 97 (06) :1611-1626
[7]   Nitric oxide in traumatic brain injury [J].
Cherian, L ;
Hlatky, R ;
Robertson, CS .
BRAIN PATHOLOGY, 2004, 14 (02) :195-201
[8]   Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans [J].
Clark, RSB ;
Kochanek, PM ;
Obrist, WD ;
Wong, HR ;
Billiar, TR ;
Wisniewski, SR ;
Marion, DW .
CRITICAL CARE MEDICINE, 1996, 24 (07) :1243-1251
[9]   Lack of effect of induction of hypothermia after acute brain injury. [J].
Clifton, GL ;
Miller, ER ;
Choi, SC ;
Levin, HS ;
McCauley, S ;
Smith, KR ;
Muizelaar, JP ;
Wagner, FC ;
Marion, DW ;
Luerssen, TG ;
Chesnut, RM ;
Schwartz, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (08) :556-563
[10]   The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats [J].
Djebaili, M ;
Guo, QM ;
Pettus, EH ;
Hoffman, SW ;
Stein, DG .
JOURNAL OF NEUROTRAUMA, 2005, 22 (01) :106-118