Neuroprotective therapy
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Updated: Oct 25, 2026

Strategies for Study of Neuroprotection from Cold-preconditioning
Published on: September 2, 2010
1Department of Neurology, University of Texas at Houston Medical School, 77030, USA.
Abstract:
The concept of neuroprotection relies on the principle that delayed neuronal injury occurs after ischemia. The phenomenon of the "ischemic cascade" has been described, and each step along this cascade provides a target for therapeutic intervention. In animal models of global and focal cerebral ischemia, numerous preclinical studies have demonstrated various agents to be neuroprotective at different steps along this cascade. A wide variety of drugs has also been studied in humans. Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They include calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilizad, anti-intercellular adhesion molecule-1 (ICAM-1) antibody, GM-1 ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and piracetam. In the future, clinicians may have an armamentarium of treatments for acute ischemic stroke at their disposal, with a combination of agents directed at different sites in the ischemic cascade being the ultimate goal.
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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