http://thejns.org/doi/full/10.3171/2017.1.FOCUS16522
- Michael Karsy, MD, PhD,
- Andrea Brock, MD, MSci,
- Jian Guan, MD,
- Phillip Taussky, MD,
- M. Yashar S. Kalani, MD, PhD, and
- Min S. Park, MD
Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah
ABBREVIATIONS AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazole propionate; ATP = adenosine 5′-triphosphate; GABA = γ-aminobutyric acid; IL = interleukin; mRS = modified Rankin Scale; 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.
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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.
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