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Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
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Clinical trials in acute ischemic stroke.

Kiyoshi Kikuchi1, Eiichiro Tanaka, Yoshinaka Murai

  • 1Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok, 10400, Thailand.

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Summary

Developing effective neurovascular protectants for acute ischemic stroke (AIS) has been challenging. Future treatments may require combination therapies and a deeper understanding of AIS pathophysiology.

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Area of Science:

  • Neurology
  • Pharmacology
  • Biomedical Research

Background:

  • Acute ischemic stroke (AIS) is a leading cause of death and disability globally.
  • Despite extensive research, developing successful neurovascular protectants for AIS has faced significant challenges, with many candidates failing in clinical trials due to lack of efficacy, poor bioavailability, or toxicity.

Purpose of the Study:

  • To review and evaluate neurovascular protectants that have undergone clinical trial evaluation for the treatment of AIS.
  • To identify the challenges and limitations in the development of AIS treatments.
  • To explore potential future directions for AIS therapeutic development.

Main Methods:

  • Comprehensive literature review of clinical trials for AIS neuroprotective agents.
  • Analysis of studies conducted between 1978 and 2014, encompassing 241 trials.
  • Evaluation of various mechanisms of action, including anti-excitotoxic, anti-inflammatory, antioxidant, and thrombolytic approaches.

Main Results:

  • Many neuroprotective agents have failed to demonstrate significant efficacy or neurovascular protection in clinical trials for AIS.
  • Approved treatments like alteplase have a narrow therapeutic window.
  • Several agents like tenecteplase, edaravone, and minocycline show future promise.

Conclusions:

  • New approaches are needed to develop effective agents that reduce brain injury in AIS, requiring a deeper understanding of its pathophysiology.
  • Combination therapy is likely to be more effective than monotherapy for future AIS treatment.
  • Innovative strategies for testing and utilizing neurovascular protectants are essential.