Cited by 254Neuroinflammation and Neurodegeneration MechanismsRenin-Angiotensin System StudiesTraumatic Brain Injury and Neurovascular Disturbances

Angiotensin II AT1 Receptor Blockade Ameliorates Brain Inflammation

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Benicky, Julius, Sánchez-Lemus, Enrique, Honda, Masaru, Pang, Tao, Orecna, Martina, Wang, Juan, Leng, Yan, Chuang, De-Maw +1 more·2011·Neuropsychopharmacology

Abstract

Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT(1) receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders.

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  • ACE-I/ARBs are capable of reducing neuroinflammation.

    “However, these agents are also capable of reducing neuroinflammation (Benicky et al, 2011;Welty et al, 2015)”

    From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Benicky et al, 2011

    The Discussion reports that ARBs reduced inflammatory responses in the brains of normotensive rats, supporting the ARB portion of the claim. The paper does not establish that ACE inhibitors reduce neuroinflammation; its findings concern AT1 receptor blockers. No page numbers are available in our copy. (LLM, conf=0.86)

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Authors
Benicky, J., Sánchez-Lemus, E., Honda, M., Pang, T., Orecna, M., Wang, J., Leng, Y., Chuang, D.-M., & Saavedra, J. M.
Affiliations
National Institutes of Health (US)
Venue
Neuropsychopharmacology
Published
2010-12-08
Volume
36
Issue
4
Pages
857-870
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W2120778240
Cited by
254
References
65
Citations by year
2026: 12 · 2025: 16 · 2024: 18 · 2023: 16 · 2022: 15 · 2021: 22 · 2020: 19 · 2019: 17 · 2018: 14 · 2017: 26 · 2016: 14 · 2015: 22 · 2014: 14 · 2013: 8 · 2012: 12
FWCI
5.42
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health
  • Japan Society for the Promotion of Science
  • National Institute of Mental Health (ZIAMH002762)
  • NHLBI Division of Intramural Research
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
candesartan, neuroinflammation, lipopolysaccharide, inflammatory cytokines, microglial activation, hypothalamic paraventricular nucleus, subfornical organ, prefrontal cortex, hippocampus, amygdala, anxiety, anorexia, anti-inflammatory activity, cerebellar granule cells, brain microvascular endothelial cells
MeSH terms
Animals, Animals, Newborn, Benzimidazoles, Biphenyl Compounds, Brain, Female, Inflammation, Lipopolysaccharides, Male, Rats, Inbred SHR, Tetrazoles, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Angiotensin, Type 1, Angiotensin II Type 1 Receptor Blockers, Rats

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