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Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation
Ángel Chamorro1, Ulrich Dirnagl2, Xabier Urra1
1Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain.
Abstract:
Treatments for acute ischaemic stroke continue to evolve after the superior value of endovascular thrombectomy was confirmed over systemic thrombolysis. Unfortunately, numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischaemic stroke, making the search for new treatments imperative. Increased awareness of the relevance of rigorous preclinical testing, and appropriate selection of study participants, might overcome the barriers to progress in stroke research. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials. Randomised controlled trials of combination treatments completed within the past 5 years have included growth factors, hypothermia, minocycline, natalizumab, fingolimod, and uric acid; the latter two drugs with alteplase produced encouraging results. Blocking of excitotoxicity is also being reassessed in clinical trials with new approaches, such as the postsynaptic density-95 inhibitor NA-1, or peritoneal dialysis to remove excess glutamate. The findings of these randomised trials are anticipated to improve treatment options and clinical outcomes in of patients with acute stroke.
Insights
New acute ischemic stroke treatments are crucial as many neuroprotective drugs fail. Research focuses on combination therapies, advanced imaging for patient selection, and prehospital trials to improve outcomes.
Area of Science:
- Neurology
- Neurosurgery
- Pharmacology
Background:
- Endovascular thrombectomy is superior to systemic thrombolysis for acute ischemic stroke.
- Numerous neuroprotective drugs have failed in clinical trials, necessitating novel therapeutic strategies.
- Improving preclinical testing and participant selection are key to advancing stroke research.
Purpose of the Study:
- To review recent advancements and ongoing research in acute ischemic stroke treatment.
- To highlight promising therapeutic avenues, including combination therapies and improved patient selection methods.
- To discuss the potential of new approaches targeting excitotoxicity and reperfusion injury.
Main Methods:
- Review of randomized controlled trials (RCTs) of combination treatments for acute ischemic stroke.
- Analysis of studies investigating neuroprotective agents, advanced brain imaging, and prehospital trial designs.
- Examination of novel strategies for blocking excitotoxicity and enhancing reperfusion.
Main Results:
- Combination therapies involving fingolimod or uric acid with alteplase show encouraging results.
- New approaches targeting excitotoxicity, such as NA-1 and peritoneal dialysis for glutamate removal, are under investigation.
- Advanced imaging and prehospital trials are being implemented to optimize treatment delivery and patient selection.
Conclusions:
- Ongoing research into combination therapies and novel neuroprotective strategies holds promise for improving acute ischemic stroke treatment.
- Optimizing patient selection through advanced imaging and refining trial methodologies are critical for future success.
- The development of effective treatments for acute ischemic stroke remains a high priority, with potential for significant clinical impact.
