title: Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation.
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.
authors.affiliation: Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain. Electronic address: achamorro@clinic.ub.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Chamorro
authors.affiliation: Departments of Neurology and Experimental Neurology and Center for Stroke Research, Charité and Excellence Cluster NeuroCure Universitätsmedizin Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases and German Center for Cardiovascular Research, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Urra
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain; Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000009:adverse effects; D009566:Nitrates / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000150:complications / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D009566:Nitrates