Skip to main content
Log in

Neuroprotective Therapies In Stroke

  • Published:
Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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

    Article  Google Scholar 

  2. 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

    Article  PubMed  CAS  Google Scholar 

  3. Grotta J. Safety and tolerability of the glutamate antagonist CGS 19755 in acute stroke patients. Stroke 1994; 25: 255

    Google Scholar 

  4. Davis SM, Albers GW, Diener H-C, et al. Termination of acute stroke studies involving selfotel treatment. Lancet 1997; 349: 32

    Article  PubMed  CAS  Google Scholar 

  5. 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

    Google Scholar 

  6. 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

    Article  PubMed  CAS  Google Scholar 

  7. Olney JW, Labruyere J, Price M. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 1989; 244: 1360–2

    Article  PubMed  CAS  Google Scholar 

  8. Allen HL, Iversen LL. Phencyclidine, dizocilpine, and cerebrocortical neurons. Science 1990; 247: 221

    Article  PubMed  CAS  Google Scholar 

  9. 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

    Article  PubMed  CAS  Google Scholar 

  10. Hall ED, Yonkers PA. Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F. Stroke 1988; 19: 340–4

    Article  PubMed  CAS  Google Scholar 

  11. The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke 1996; 27: 1453–8

    Article  Google Scholar 

  12. Zivin JA, Choi DW. Stroke therapy. Sci Am 1991; 265: 56–63

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Article  PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. 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

    CAS  Google Scholar 

  18. 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

    Article  PubMed  CAS  Google Scholar 

  19. Lyden PD, Hedges B. Protective effect of synaptic inhibition during cerebral ischemia. Stroke 1992; 23: 1463–70

    Article  PubMed  CAS  Google Scholar 

  20. Zivin JA, Grotta JC. Animal stroke models: they are relevant to human disease. Stroke 1990; 21: 981–3

    Article  PubMed  CAS  Google Scholar 

  21. Wiebers DO, Adams Jr HP, Whisnant JP. Animal models of stroke: are they relevant to human disease? Stroke 1989; 21: 1–3

    Article  Google Scholar 

  22. Grotta J. Rodent models of stroke limitations: what can we learn from recent clinical trials of thrombolysis? Arch Neurol 1996; 53: 1067–9

    Article  PubMed  CAS  Google Scholar 

  23. Ginsberg MD. The validity of rodent brain-ischemia models is self-evident. Arch Neurol 1996; 53: 1065–7

    Article  PubMed  CAS  Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Zivin JA, Mazzarella V. Tissue plasminogen activator plus glutamate antagonist improves outcome after embolie stroke. Arch Neurol 1991; 48: 1235–8

    Article  PubMed  CAS  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. del Zoppo G. Thrombolytic therapy in the treatment of stroke. Drugs 1997; 54 Suppl. 3:90–99

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zivin, J.A. Neuroprotective Therapies In Stroke. Drugs 54 (Suppl 3), 83–89 (1997). https://doi.org/10.2165/00003495-199700543-00012

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199700543-00012

Keywords

Navigation