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Therapeutic Strategies Harnessing Oxidative Stress to Treat Stroke

  • Gina Hadley
  • Ain A. Neuhaus
  • Alastair M. BuchanEmail author
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Oxidative stress is a major mechanism responsible for damage in ischemic stroke. Other than tissue plasminogen activator and antiplatelet agents, no pharmacological interventions have been translated into an effective treatment for stroke. As yet, there have been no unequivocally successful clinical applications of antioxidants to scavenge reactive oxygen or nitrogen species (ROS/RNS) in stroke, with some even suggested to have a detrimental effect.

Edaravone, a low-molecular weight scavenger of hydroxyl, peroxyl, and superoxide radicals that readily crosses the blood–brain barrier, was approved in 2001 in Japan for use in ischemic stroke within 24 h of the attack. However, other notable compounds such as NXY-059, a nitrone with free radical scavenging ability that fufilled nearly all of the Stroke Therapy Industry Roundtable (STAIR) criteria, still failed to make it to the clinic. NADPH oxidase inhibitors have shown promise, but are yet to be validated in clinical trials. Any prospective neuroprotective agent targeting oxidative stress would buy time to delay the ischaemic cascade, pending imaging to permit definitive restoration of blood flow.

A small molecule inhibitor of oxidative stress is unlikely to provide the panacea for ischemic stroke. Instead, targeting the ischemic cascade and resultant oxidative stress at its origin, in combination with optimization of physiological parameters and consideration of the neurovascular unit as a whole, is likely to be more effective than mere damage limitation. This chapter will discuss recent and current experimental and clinical data on therapeutic strategies targeting oxidative stress in stroke.

Keywords

Animal studies Antioxidant Clinical trials Hypothermia Edaravone Free radical Ischemic stroke Neuroprotection Neurovascular unit NXY-059 Oxidative stress Recombinant tissue plasminogen activator Translational 

Abbreviations

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASA

Acetylsalicylic acid

AT-1

Angiotensin-1 receptor 1

AVASAS

Aspirin versus ascorbic acid plus aspirin in stroke

DNA

Deoxyribonucleic acid

EAAT-1

Excitatory amino acid transporter-1

HMG-CoA

3-Hydroxy-3-methyl-glutaryl-CoA reductase

HO

Hydroxyl radical

H2O2

Hydrogen peroxide

mRS

Modified Rankin Scale

NADPH

Nicotinamide adenine dinucleotide phosphate

NDMA

N-Methyl-d-aspartate

NIHSS

National Institutes of Health Stroke Scale

NO

Nitric oxide

NOS

Nitric oxide synthase

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

rtPA

Recombinant tissue plasminogen activator

SOD

Superoxide dismutase

VISTA

Virtual International Stroke Trials Archive

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Gina Hadley
    • 1
  • Ain A. Neuhaus
    • 1
  • Alastair M. Buchan
    • 1
    Email author
  1. 1.Acute Stroke Programme, Radcliffe Department of MedicineJohn Radcliffe Hospital, University of OxfordOxfordUK

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