The role of the brain renin-angiotensin system (RAS) in mild traumatic brain injury (TBI)
Abstract
There is considerable interest in traumatic brain injury (TBI) induced by repeated concussions suffered by athletes in sports, military personnel from combat-and non-combat related activities, and civilian populations who suffer head injuries from accidents and domestic violence. Although the renin-angiotensin system (RAS) is primarily a systemic cardiovascular regulatory system that, when dysregulated, causes hypertension and cardiovascular pathology, the brain contains a local RAS that plays a critical role in the pathophysiology of several neurodegenerative diseases. This local RAS includes receptors for angiotensin (Ang) II within the brain parenchyma, as well as on circumventricular organs outside the blood-brain-barrier. The brain RAS acts primarily via the type 1 Ang II receptor (AT 1 R), exacerbating insults and pathology. With TBI, the brain RAS may contribute to permanent brain damage, especially when a second TBI occurs before the brain recovers from an initial injury. Agents are needed that minimize the extent of injury from an acute TBI, reducing TBI-mediated permanent brain damage. This review discusses how activation of the brain RAS following TBI contributes to this damage, and how drugs that counteract activation of the AT 1 R including AT 1 R blockers (ARBs), renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, and agonists at type 2 Ang II receptors (AT 2) and at Ang (1-7) receptors (Mas) can potentially ameliorate TBI-induced brain damage.
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Relatively independent RAS exists in almost all organs and tissues and can play a local role through paracrine/autocrine.
“Later, it was gradually discovered that relatively independent RAS in almost all organs and tissues can play a local role in many organs and tissues through paracrine/autocrine [15–21].”
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- Authors
- Vadhan, J. D., & Speth, R. C.
- Affiliations
- Nova Southeastern University (US)
- Georgetown University (US)
- Corresponding author
- Speth, Robert C.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 218
- Pages
- 107684
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W3087212224
- Cited by
- 42
- References
- 276
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 8
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- brain renin-angiotensin system, mild traumatic brain injury, repeated concussions, angiotensin II type 1 receptor, ACE inhibitors, renin inhibitors, angiotensin II type 2 receptor, angiotensin-(1-7), Mas receptor, circumventricular organs, brain damage, neuroprotection
- MeSH terms
- Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Brain Concussion, Humans, Renin-Angiotensin System, Angiotensin Receptor Antagonists
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