Cited by 380Nitric Oxide and Endothelin EffectsTraumatic Brain Injury and Neurovascular DisturbancesNeuroprotection in Cerebral Ischemia

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The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside

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Garry, P.S., Ezra, M., Rowland, M.J., Westbrook, J., Pattinson, K.T.S.·2015·Experimental Neurology

DOI 10.1016/j.expneurol.2014.10.017

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Abstract

Nitric oxide (NO) is a key signalling molecule in the regulation of cerebral blood flow. This review summarises current evidence regarding the role of NO in the regulation of cerebral blood flow at rest, under physiological conditions, and after brain injury, focusing on subarachnoid haemorrhage, traumatic brain injury, and ischaemic stroke and following cardiac arrest. We also review the role of NO in the response to hypoxic insult in the developing brain. NO depletion in ischaemic brain tissue plays a pivotal role in the development of subsequent morbidity and mortality through microcirculatory disturbance and disordered blood flow regulation. NO derived from endothelial nitric oxide synthase (eNOS) appears to have neuroprotective properties. However NO derived from inducible nitric oxide synthase (iNOS) may have neurotoxic effects. Cerebral NO donor agents, for example sodium nitrite, appear to replicate the effects of eNOS derived NO, and therefore have neuroprotective properties. This is true in both the adult and immature brain. We conclude that these agents should be further investigated as targeted pharmacotherapy to protect against secondary brain injury.

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Authors: Garry, P. S., Ezra, M., Rowland, M. J., Westbrook, J., & Pattinson, K. T. S.
Affiliations: John Radcliffe Hospital (GB)
Corresponding author: Garry, P.S.
ORCID: Ezra, M.
Rowland, M.J.
Pattinson, K.T.S.
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2015-01
Volume: 263
Pages: 235-243
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1016/j.expneurol.2014.10.017
OpenAlex: W2055065148
Cited by: 380
References: 109
Citations by year: 2026: 13 · 2025: 26 · 2024: 25 · 2023: 34 · 2022: 35 · 2021: 51 · 2020: 53 · 2019: 36 · 2018: 28 · 2017: 36 · 2016: 30 · 2015: 13
FWCI: 3.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
Locations: Experimental Neurology (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Oxford University Clinical Academic Graduate School
Medical Research Council
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords: nitric oxide, cerebral autoregulation, brain injury, subarachnoid hemorrhage, traumatic brain injury, ischemic stroke, cardiac arrest, hypoxia, developing brain, endothelial nitric oxide synthase, inducible nitric oxide synthase, neuroprotection, sodium nitrite, nitric oxide donors, secondary brain injury, microcirculation
MeSH terms: Animals, Brain Injuries, Cerebrovascular Circulation, Humans, Nitric Oxide, Signal Transduction, Nitric Oxide Synthase

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The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside

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