This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dyker, A. G. Articles by Lees, K. R. Search for Related Content PubMed PubMed Citation Articles by Dyker, A. G. Articles by Lees, K. R.

(Stroke. 1998;29:535-542.)
© 1998 American Heart Association, Inc.

Comments, Opinions, and Reviews

Duration of Neuroprotective Treatment for Ischemic Stroke

A. G. Dyker, BSc, MRCP; K. R. Lees, BSc, MD, FRCP

From the Acute Stroke Unit, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.

Correspondence to Dr A.G. Dyker, Acute Stroke Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK. E-mail AD47Q{at}clinmed.gla.ac.uk

Background—The therapeutic time window for thrombolysis appears to be extremely short, probably because of the hemorrhagic complications associated with late reperfusion of ischemic brain tissue. Other neuroprotective forms of treatment continue to be developed, although their efficacy has yet to be conclusively proved in patients. The duration of treatment in recent phase 3 trials ranges from a single bolus injection to 12 weeks of oral therapy.

Summary of Review—In this article we discuss the factors that should influence the choice of route and duration of treatment. Excitotoxic injury following stroke evolves over at least 4 hours in rodents and possibly beyond 48 hours in humans. In addition, autoregulation and local cerebral perfusion are deranged for approximately 72 hours in patients with stroke. Neuroprotection should provide cover during this critical time.

Conclusions—Important considerations influencing drug administration should include the pharmacology of the compound (pharmacokinetics, mechanism of action, preclinical toxicity, and pharmaceutical properties), its safety and tolerability in patients, and the likelihood of continuing or recurrent cerebral ischemia, along with practical issues such as ease of administration and interactions with early rehabilitation and other therapies. Optimization of treatment will be possible only when neuroprotection is confirmed to be effective.

Key Words: cerebral ischemia • neuroprotection • glutamates • N-methyl-D-aspartate • drug therapy • penumbra

This article has been cited by other articles:

				H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]

				D. J. Gladstone, S. E. Black, and A. M. Hakim Toward Wisdom From Failure: Lessons From Neuroprotective Stroke Trials and New Therapeutic Directions Stroke, August 1, 2002; 33(8): 2123 - 2136. [Abstract] [Full Text] [PDF]

				S.-H. Yang, E. Perez, J. Cutright, R. Liu, Z. He, A. L. Day, and J. W. Simpkins Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model J Appl Physiol, January 1, 2002; 92(1): 195 - 201. [Abstract] [Full Text] [PDF]

				C. S. Kidwell, D. S. Liebeskind, S. Starkman, and J. L. Saver Trends in Acute Ischemic Stroke Trials Through the 20th Century Stroke, June 1, 2001; 32(6): 1349 - 1359. [Abstract] [Full Text] [PDF]

				K. R. Lees, A. G. Dyker, A. Sharma, G. A. Ford, M. E. Ardron, and D. G. Grosset Tolerability of the Low-Affinity, Use-Dependent NMDA Antagonist AR-R15896AR in Stroke Patients : A Dose-Ranging Study Stroke, February 1, 2001; 32(2): 466 - 472. [Abstract] [Full Text] [PDF]

				A. J. Williams, J. R. Dave, J. B. Phillips, Y. Lin, R. T. McCabe, and F. C. Tortella Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-D-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 378 - 386. [Abstract] [Full Text]

				D. Reglodi, A. Somogyvari-Vigh, S. Vigh, T. Kozicz, A. Arimura, and S. P. Finklestein Delayed Systemic Administration of PACAP38 Is Neuroprotective in Transient Middle Cerebral Artery Occlusion in the Rat Editorial Comment Stroke, June 1, 2000; 31(6): 1411 - 1417. [Abstract] [Full Text] [PDF]

				C. S. Kidwell, S. Starkman, M. Eckstein, K. Weems, and J. L. Saver Identifying Stroke in the Field : Prospective Validation of the Los Angeles Prehospital Stroke Screen (LAPSS) Stroke, January 1, 2000; 31(1): 71 - 76. [Abstract] [Full Text] [PDF]

				J. Perl II, J. A. Tkach, M. Porras-Jimenez, M. Lieber, N. Obuchowski, J. S. Ross, X. P. Ding, P. M Ruggieri, D. M. Shearer, K. Khajavi, et al. Hemorrhage Detected Using MR Imaging in the Setting of Acute Stroke: An In Vivo Model AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1863 - 1870. [Abstract] [Full Text]

				G DEVUYST and J BOGOUSSLAVSKY Recent progress in drug treatment for acute stroke J. Neurol. Neurosurg. Psychiatry, October 1, 1999; 67(4): 420 - 425. [Full Text] [PDF]

				P.-E. Chabrier, M. Auguet, B. Spinnewyn, S. Auvin, S. Cornet, C. Demerle-Pallardy, C. Guilmard-Favre, J.-G. Marin, B. Pignol, V. Gillard-Roubert, et al. BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: A promising neuroprotective strategy PNAS, September 14, 1999; 96(19): 10824 - 10829. [Abstract] [Full Text] [PDF]