title: Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke.
abstract: Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: Michael
authors.initials: M
authors.lastname: Karsy
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brock
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: Phillip
authors.initials: P
authors.lastname: Taussky
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: M Yashar S
authors.initials: MY
authors.lastname: Kalani
authors.affiliation: Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
authors.forename: Min S
authors.initials: MS
authors.lastname: Park
mesh_terms: D000818:Animals; D004333:Drug Administration Routes; D006801:Humans; D061185:Mechanical Thrombolysis / Q000379:methods; D008967:Molecular Biology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000235:genetics / Q000628:therapy*
chemical_list: D018696:Neuroprotective Agents
keywords: AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazole propionate; ATP = adenosine 5′-triphosphate; GABA = γ-aminobutyric acid; IL = interleukin; NIHSS = National Institutes of Health Stroke Scale; NMDA = N-methyl-d-aspartate; RCT = randomized controlled trial; SUR1-TRPM4 = sulfonylurea receptor 1–transient receptor potential melastatin 4; TPA = tissue plasminogen activator; cerebrovascular accident; intracerebral hemorrhage; intraparenchymal hemorrhage; mRS = modified Rankin Scale; neuroprotection; stroke