Neuroprotection for Ischemic Stroke: Two Decades of Success and Failure

被引:250
作者
Cheng Y.D. [1 ]
Al-Khoury L. [1 ]
Zivin J.A. [1 ]
机构
[1] Stroke Center, University of California School of Medicine, University of California San Diego, La Jolla
来源
NeuroRX | 2004年 / 1卷 / 1期
关键词
anti-inflammatory agents; free radical scavengers; glutamate antagonists; ion channel blocks; neural stem cells; Neuroprotection trials; neurotrophic factors;
D O I
10.1602/neurorx.1.1.36
中图分类号
学科分类号
摘要
Alteplase (rt-PA) is the first therapy successfully developed for acute stroke therapy. The success of rt-PA spurred development of new avenues for acute stroke management. For the last two decades, a great deal of attention has been paid to neuroprotective therapies. Initial preclinical studies demonstrated numerous drugs are effective for treating acute stroke in animal models; however, subsequent clinical trials have been frustrating, and none of the agents has proven effective. The various outcomes of preclinical and clinical trials have been the subject of much discussion. In this article, we review some key neuroprotective trials and the possible reasons for their failures. By identifying the discrepancies between preclinical studies and clinical trials, we may be able to set guidelines for future effective trials. © 2004 The American Society for Experimental NeuroTherapeutics, Inc.
引用
收藏
页码:36 / 45
页数:9
相关论文
共 92 条
  • [11] Guyot L., Diaz F., O'Regan M., Song D., Phillis J., Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model, Neurosci Lett, 299, pp. 37-40, (2001)
  • [12] Boast C., Gerhardt B., Pastor G., Lehmann J., Etienne P., Liebman J., The N-methyl-d-aspartate antagonist CGS19755 and CPP reduce ischemic brain damage in gerbils, Brain Res, 442, pp. 345-348, (1988)
  • [13] Gotti B., Duverger D., Bertin J., Carter C., Dupont R., Frost J., Et al., Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. 1. Evidence for efficacy in models of focal cerebral ischemia, J Pharmacol Exp Ther, 247, pp. 1211-1221, (1988)
  • [14] O'Neill M., Hicks C., Ward M., Neuroprotective effects of 7-nitroindazole in gerbil model of global cerebral ischemia, Eur J Pharmacol, 310, pp. 115-122, (1996)
  • [15] Patat A., Molinjier P., Hergueta T., Brohier S., Zieleniuk I., Danjou P., Et al., Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist, Int Clin Psychopharmacol, 9, pp. 155-162, (1994)
  • [16] Aronowski J., Ostrow P., Samways E., Strong R., Zivin J., Grotta J., Graded bioassay for demonstration of brain rescue from experimental acute ischemia in rats, Stroke, 25, pp. 2235-2240, (1994)
  • [17] Cohen R., Hasegawa Y., Fisher M., Effects of a novel NMDA receptor antagonist on experimental stroke quantitatively assessed by spectral EEG and infarct volume, Neurol Res, 16, pp. 443-448, (1994)
  • [18] Muir K., New experimental data on the efficacy of pharmacological magnesium infusions in cerebral infarcts [abstract], Magnes Res, 11, pp. 43-56, (1998)
  • [19] Clark W., Madden K., Rothlein R., Zivin J., Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule, J Neurosurg, 75, pp. 623-627, (1991)
  • [20] Zhang R., Chopp M., Jiang N., Tang W., Prostak J., Manning A., Et al., Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat, Stroke, 26, pp. 1438-1443, (1995)