Manifestation of renin angiotensin system modulation in traumatic brain injury

Mirzahosseini, Golnoush; Ismael, Saifudeen; Ahmed, Heba A.; Ishrat, Tauheed

doi:10.1007/s11011-021-00728-1

Cited by 15 publications

(13 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 and 3 ), suggesting the essential role of the Ang II/AT 1 receptor system in DPN development. The downstream signals of AT 1 receptor activation involved in DPN development remain to be investigated in future studies, although stimulation of AT 1 receptors is known to cause oxidative stress 44 which could be involved in the pathogenesis of DPN 45 . In our clinical study, the number of T2DM patients receiving aliskiren, a renin inhibitor, was quite limited, so that the effect of aliskiren on DPN development could not be analyzed.…”

Section: Discussionmentioning

confidence: 99%

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

Iwane,

Nemoto,

Miyamoto

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni’s test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and β-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

Iwane,

Nemoto,

Miyamoto

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…There is therefore significant evidence to suggest that sACE, Ang II, and ATR1 play a significant role in brain inflammation, with consequences for various brain disorders, forming a pathological axis of the RAS. In contrast, ACE2, Ang 1-7, and AT2R are considered to be the protective axis of the RAS, with activation of ACE2 and its downstream elements, promoting protective responses through the Mas receptor, leading to antioxidant and anti-inflammatory effects (Miners et al, 2020), and increasing vascular stability (Valencia et al, 2022).…”

Section: Ta B L Ementioning

confidence: 99%

“…Up‐regulation of ATR1 mediates the effects of Ang II, including the release of proinflammatory cytokines, cell death, oxidative stress, and vasoconstriction. As ATR1 is highly expressed in neurons and astrocytes, it has been suggested that the modulation of this pathway in traumatic brain injury, which triggers the release of inflammatory mediators (cytokines), may aggravate the cerebral damage (Mirzahosseini et al, 2021). ARBs are also reported to reduce common injury mechanisms, including decreasing excessive inflammation, preventing immune responses, and increasing cerebrovascular flow (Saavedra, 2021).…”

Section: Ace and Ace2 In Disorders Of The Brainmentioning

confidence: 99%

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

Santiago

Parra

Nani

et al. 2023

Journal of Neurochemistry

View full text Add to dashboard Cite

The renin‐angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential roles in the brain only being recognized more recently. Angiotensin‐I‐converting enzyme (ACE) is the main component of the RAS, and it has been implicated in various disorders of the brain. ACE and other RAS components, including the related enzyme ACE2, angiotensin peptides and their respective receptors, can participate in the pathological state, as well as with potential to contribute to neuroprotection and/or to complement existing treatments for psychiatric illness. In this narrative review, we aimed to identify the main studies describing the functions of the RAS and ACEs in the brain and their association with brain disorders. These include neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. We also discuss the possible association of a functional polymorphism of the ACE gene with these brain diseases and the relevance of the neuroprotective and anti‐inflammatory properties of ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Based on this, we conclude that there is significant potential value to the inclusion of ACEis and/or ARBs as a novel integrated approach for the treatment of various disorders of the brain, and particularly for psychiatric illness.

show abstract

“…This systematic review provides the first MA of currently available evidence and is more comprehensive than a recently published review 88 , which does not include all available evidence on the RAS, such as ACEi. All available data was extracted, including the data presented only graphically.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Báron

Skrobot

Palmer

et al. 2022

Journal of Neurotrauma

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a major health concern and leading cause of death and disability in young adults in the UK and worldwide, however, there is a paucity of disease modifying therapies for the treatment of TBI. This review investigates the potential of the reninangiotensin system (RAS) as a treatment pathway for traumatic brain injury (TBI) in adults.Relevant electronic databases were searched on 18 December 2019, updated 16 May 2021. All English language articles with adult human or animal populations investigating RAS drugs as an intervention for TBI or reporting genetic evidence relevant to the RAS and TBI were screened.Eighteen preclinical RCTs (n=2269) and 2 clinical cohort studies (n=771) were included. Metaanalyses of 6 preclinical randomised-controlled trials (n=99) indicated candesartan improved neurological function short-term (<7 days: standardised mean difference (SMD) 0.61, 95% confidence interval (CI) 0.19 -1.03, I2=0%) and long-term (≥7 days: SMD 1.06, 95% CI 0.38; 1.73, I2=0%) post-TBI. Findings were similar for most secondary outcomes. There was a suggestion of benefit from other RAS-targeting drugs, although evidence was limited due to few small studies. There was insufficient evidence to enable strong assessment of these drugs on mortality post-TBI. We conclude that angiotensin-receptor blockers, especially candesartan, show positive outcomes post-TBI in preclinical studies with moderate quality of evidence (GRADE). More research into the effect of regulatory-RAS targeting drugs is needed. Clinical trials of candesartan following TBI are recommended, due to strong and consistent evidence of neuroprotection shown by these preclinical studies.

show abstract

Manifestation of renin angiotensin system modulation in traumatic brain injury

Cited by 15 publications

References 65 publications

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About