Neuroprotective therapy

S L Hickenbottom1, J Grotta

  • 1Department of Neurology, University of Texas at Houston Medical School, 77030, USA.

Seminars in Neurology
|February 5, 1999
PubMed

Insights

Neuroprotection aims to prevent delayed brain cell death after stroke by targeting the ischemic cascade. While many agents show promise in animal models, human trials yield mixed results, necessitating further research for effective stroke treatments.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Delayed neuronal injury after ischemia, known as the "ischemic cascade," presents therapeutic targets.
  • Preclinical studies in animal models demonstrate neuroprotective potential of various agents against cerebral ischemia.

Purpose of the Study:

  • To review the therapeutic strategies targeting the ischemic cascade for neuroprotection.
  • To evaluate the efficacy of neuroprotective agents in human clinical trials.

Main Methods:

  • Review of preclinical studies in animal models of global and focal cerebral ischemia.
  • Analysis of human clinical trial data for ten classes of neuroprotective agents that reached Phase III efficacy trials.

Main Results:

  • Numerous agents showed neuroprotection in animal models targeting different steps of the ischemic cascade.
  • Ten classes of neuroprotective agents (e.g., calcium channel antagonists, NMDA receptor antagonists, tirilizad, ICAM-1 antibody) have reached Phase III trials with mixed results.

Conclusions:

  • Current neuroprotective agents have shown limited success in human trials for acute ischemic stroke.
  • Future stroke treatment may involve combination therapies targeting multiple sites within the ischemic cascade.

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