Summary
Neuroprotective drugs are known to reduce neurological damage in animal models of stroke, but none are generally accepted for the treatment of patients with acute stroke. Thrombolytic therapy with alteplase (recombinant tissue-type plasminogen activator; rt-PA) has been shown to improve outcomes in patients with stroke, but it must be given quite rapidly after stroke onset. The efficacy of alteplase therapy has proven that acute treatment is possible, and methods used in those trials will be applicable to neuroprotective development.
A variety of neuroprotective drugs have already been tested and more trials are likely. Glutamate antagonists have been most extensively evaluated, but they are relatively disappointing since they have phencyclidine-like adverse events that limit the tolerable doses. Several other classes of neuroprotectives are in development, although their mechanisms of action are not well established. Combinations of neuroprotectives and thrombolytics are likely to be tested in clinical trials in the near future.
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References
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581–7
Olney JW, Ho OL, Rhee V. Cytotoxic effects of acidic and sulfur containing amino acids on infant mouse central nervous system. Exp Brain Res 1971; 14: 61–76
Grotta J. Safety and tolerability of the glutamate antagonist CGS 19755 in acute stroke patients. Stroke 1994; 25: 255
Davis SM, Albers GW, Diener H-C, et al. Termination of acute stroke studies involving selfotel treatment. Lancet 1997; 349: 32
Teasdale G, Wagstaff A, on behalf of the 1102-005 (CERESTAT®) Studies Group. Safety of extended administration to head injured patients of aptiganel HCl (CERESTAT®), a non-competitive NMDA antagonist. J Neurol, Neurosurg Psychiatry 1996; 61: 547–8
Grotta J, Clark W, Coull B, et al. Safety and tolerability of the glutamate antagonists CGS 19755 (Selfotel) in patients with acute ischemic stroke. Stroke 1995; 26: 602–5
Olney JW, Labruyere J, Price M. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 1989; 244: 1360–2
Allen HL, Iversen LL. Phencyclidine, dizocilpine, and cerebrocortical neurons. Science 1990; 247: 221
Buchan AM, Li H, Cho S, et al. Blockade of the AMPA receptor prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats. Neurosci Lett 1991; 132: 255–8
Hall ED, Yonkers PA. Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F. Stroke 1988; 19: 340–4
The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke 1996; 27: 1453–8
Zivin JA, Choi DW. Stroke therapy. Sci Am 1991; 265: 56–63
Clark WM, Madden KP, Rothlein R, et al. Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule. J Neurosurg 1991; 75: 623–7
Zhang RL, Chopp M, Li Y, et al. Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology 1994; 44: 1747–51
Lindsberg PJ, Sirén A-L, Feuerstein GZ, et al. Antagonism of neutrophil adherence in the deteriorating stroke model in rabbits. J Neurosurg 1995; 82: 269–77
Aronowski J, Strong R, Grotta JC. Combined neuroprotection and reperfusion therapy for stroke. Effect of lubeluzole and diaspirin cross-linked hemoglobin in experimental focal ischemia. Stroke 1996; 27: 1571–7
DeRyck M, Keersmaekers R, Duytschaever H, et al. Lubeluzole protects sensorimotor function and reduces infarct size in a photochemical stroke model in rats. J Pharmacol Exp Ther 1996; 279: 748–58
Diener HC, Hacke W, Hennerici M, et al. Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II trial. Stroke 1996; 27: 76–81
Lyden PD, Hedges B. Protective effect of synaptic inhibition during cerebral ischemia. Stroke 1992; 23: 1463–70
Zivin JA, Grotta JC. Animal stroke models: they are relevant to human disease. Stroke 1990; 21: 981–3
Wiebers DO, Adams Jr HP, Whisnant JP. Animal models of stroke: are they relevant to human disease? Stroke 1989; 21: 1–3
Grotta J. Rodent models of stroke limitations: what can we learn from recent clinical trials of thrombolysis? Arch Neurol 1996; 53: 1067–9
Ginsberg MD. The validity of rodent brain-ischemia models is self-evident. Arch Neurol 1996; 53: 1065–7
Brott TG, Haley Jr EC, Levy DE, et al. Urgent therapy for stroke. Part 1. Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992; 23: 632–40
Zivin JA, Mazzarella V. Tissue plasminogen activator plus glutamate antagonist improves outcome after embolie stroke. Arch Neurol 1991; 48: 1235–8
Bowes MP, Rothlein R, Fagan SC, et al. Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology 1995; 45: 815–9
del Zoppo G. Thrombolytic therapy in the treatment of stroke. Drugs 1997; 54 Suppl. 3:90–99
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Zivin, J.A. Neuroprotective Therapies In Stroke. Drugs 54 (Suppl 3), 83–89 (1997). https://doi.org/10.2165/00003495-199700543-00012
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DOI: https://doi.org/10.2165/00003495-199700543-00012