The potential role of renin-angiotensin system in mild traumatic brain injury

Barros, João Luís Vieira Monteiro de; Cardoso, Maíra Glória de Freitas; Machado, Caroline Amaral; Vieira, Érica Leandro Marciano; Faleiro, Rodrigo Moreira; Pedroso, Vinicius Sousa Pietra; Silva, Ana Cristina Simões e; Souza, Leonardo Cruz de; Teixeira, Antônio Lúcio; Miranda, Aline Silva de

doi:10.1007/s10072-021-05856-1

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…Besides Saa1, Ace was previously found to be upregulated in the blood of TBI patients 64 . Since the renin‐angiotensin system (RAS) is an important modulator of inflammation (de Barros et al 64 ), increased Ace levels in the plasma might imply a systemic inflammatory response. Interestingly, Ace levels were only increased in the plasma of TBI‐treated but not AS + TBI‐treated mice.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, Saa1 was recently identified as a novel biomarker in TBI patients, and the Saa1‐TLR4 (toll‐like receptor 4) axis provides an important link between (peripheral) inflammation and the outcome of TBI patients. Besides Saa1, Ace was previously found to be upregulated in the blood of TBI patients 64 . Since the renin‐angiotensin system (RAS) is an important modulator of inflammation (de Barros et al 64 ), increased Ace levels in the plasma might imply a systemic inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

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Acute stress modulates the outcome of traumatic brain injury‐associated gene expression and behavioral responses

Reiners,

Leopold,

Hallebach

et al. 2023

The FASEB Journal

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Psychological stress and traumatic brain injury (TBI) result in long‐lasting emotional and behavioral impairments in patients. So far, the interaction of psychological stress with TBI not only in the brain but also in peripheral organs is poorly understood. Herein, the impact of acute stress (AS) occurring immediately before TBI is investigated. For this, a mouse model of restraint stress and TBI was employed, and their influence on behavior and gene expression in brain regions, the hypothalamic–pituitary–adrenal (HPA) axis, and peripheral organs was analyzed. Results demonstrate that, compared to single AS or TBI exposure, mice treated with AS prior to TBI showed sex‐specific alterations in body weight, memory function, and locomotion. The induction of immediate early genes (IEGs, e.g., c‐Fos) by TBI was modulated by previous AS in several brain regions. Furthermore, IEG upregulation along the HPA axis (e.g., pituitary, adrenal glands) and other peripheral organs (e.g., heart) was modulated by AS–TBI interaction. Proteomics of plasma samples revealed proteins potentially mediating this interaction. Finally, the deletion of Atf3 diminished the TBI‐induced induction of IEGs in peripheral organs but left them largely unaltered in the brain. In summary, AS immediately before brain injury affects the brain and, to a strong degree, also responses in peripheral organs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acute stress modulates the outcome of traumatic brain injury‐associated gene expression and behavioral responses

Reiners,

Leopold,

Hallebach

et al. 2023

The FASEB Journal

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“… 2) Fourth, published heterogeneous human studies are not considered strong evidence due to different drug usage among patients and varying effects of AT1R, AT2R, and AT4R on TBI. 14) Fifth, drug dosage is an important aspect. Previous animal studies used low-dose candesartan and telmisartan without significant effects on blood pressure.…”

Section: Ras-related Drugs In Tbimentioning

confidence: 99%

Mini-Review: Role of Drugs Affecting Renin-Angiotensin System (RAS) in Traumatic Brain Injury (TBI): What We Know and What We Should Know

Sarpoolaki

Vafaei

Fattahi

et al. 2023

Korean J Neurotrauma

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Traumatic brain injuries (TBIs) are among the most important clinical and research areas in neurosurgery, owing to their devastating effects and high prevalence. Over the last few decades, there has been increasing research on the complex pathophysiology of TBI and secondary injuries following TBI. A growing body of evidence has shown that the renin-angiotensin system (RAS), a well-known cardiovascular regulatory pathway, plays a role in TBI pathophysiology. Acknowledging these complex and poorly understood pathways and their role in TBI could help design new clinical trials involving drugs that alter the RAS network, most notably angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. This study aimed to briefly review the molecular, animal, and human studies on these drugs in TBI and provide a clear vision for researchers to fill knowledge gaps in the future.

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