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

Garry, P.S.; Ezra, M.; Rowland, M.J.; Westbrook, J.; Pattinson, K.T.S.

doi:10.1016/j.expneurol.2014.10.017

Cited by 380Nitric Oxide and Endothelin EffectsTraumatic Brain Injury and Neurovascular DisturbancesNeurological Disorders and Treatments

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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Nitric oxide species at low doses is critical for maintaining healthy microglia and neuron function, but at high doses can induce necrosis or apoptosis.
“Nitric oxide species at low doses is critical for maintaining healthy microglia and neuron function, but at high doses can induce necrosis or apoptosis [53].”
From Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation (2019) · cites this paper as [53]

1 retracted

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Neuronal Cell Death
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RETRACTED: Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration
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Retracted
Neuroinflammation and Microvascular Dysfunction After Experimental Subarachnoid Hemorrhage: Emerging Components of Early Brain Injury Related to Outcome
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Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition
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Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications
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Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease
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Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke
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Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation
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Comparative Response of Brain to Chronic Hypoxia and Hyperoxia
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Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm
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Photobiomodulation and nitric oxide signaling
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Apelin-13 Protects against Ischemic Blood-Brain Barrier Damage through the Effects of Aquaporin-4
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Cardiovascular Disease, the Nitric Oxide Pathway and Risk of Cognitive Impairment and Dementia
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Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
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AST-120 Reduces Neuroinflammation Induced by Indoxyl Sulfate in Glial Cells
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Role of Nitric Oxide and Hydrogen Sulfide in Ischemic Stroke and the Emergent Epigenetic Underpinnings
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Deficiency of Endothelial Nitric Oxide Synthase (eNOS) Exacerbates Brain Damage and Cognitive Deficit in A Mouse Model of Vascular Dementia
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Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus
Oliveira, A. C., Pereira, M. C., Santana, L. N. D. S., Fernandes, R. M., Teixeira, F. B., de Oliveira, G. B., Fernandes, L. M. P., Fontes-Júnior, E. A., Prediger, R. D., Lopez, M. E. C., et al. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115581960 · Cited by 65 · see citing works
The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease, Parkinson’s Disease and Multiple Sclerosis
Paoletti, F. P., Simoni, S., Parnetti, L., & Gaetani, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094958 · Cited by 65 · see citing works
Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework
Stotesbury, H., Kawadler, J. M., Hales, P. W., Saunders, D. E., Clark, C. A., & Kirkham, F. J. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00871 · Cited by 66 · see citing works
Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet
Bernier, M., Wahl, D., Ali, A., Allard, J. S., Faulkner, S., Wnorowski, A., Sanghvi, M., Moaddel, R., Alfaras, I., Mattison, J. A., et al. (2016) · Aging · doi:10.18632/aging.100942 · Cited by 63 · see citing works
Moringa oleifera supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose
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Traumatic Brain Injury: A Forensic Approach: A Literature Review
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Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection
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Retracted
Nanomaterials alleviating redox stress in neurological diseases: mechanisms and applications
Jiang, Y., Kang, Y., Liu, J., Yin, S., Huang, Z.-D., & Shao, L. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01434-5 · Cited by 59 · see citing works
NO, CO and H2S: A trinacrium of bioactive gases in the brain
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Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat
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Chronic copper exposure leads to hippocampus oxidative stress and impaired learning and memory in male and female rats
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Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species
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Thyroid hormone treatment activates protective pathways in both in vivo and in vitro models of neuronal injury
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Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits Induced by Experimental Traumatic 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 › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
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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