PMID- 37759139
OWN - NLM
STAT- MEDLINE
DCOM- 20231130
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 20
IP  - 6
DP  - 2023 Oct
TI  - The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.
PG  - 1565-1591
LID - 10.1007/s13311-023-01435-8 [doi]
AB  - Traumatic brain injury (TBI) is a major public health problem, with limited 
      pharmacological options available beyond symptomatic relief. The renin 
      angiotensin system (RAS) is primarily known as a systemic endocrine regulatory 
      system, with major roles controlling blood pressure and fluid homeostasis. Drugs 
      that target the RAS are used to treat hypertension, heart failure and kidney 
      disorders. They have now been used chronically by millions of people and have a 
      favorable safety profile. In addition to the systemic RAS, it is now appreciated 
      that many different organ systems, including the brain, have their own local RAS. 
      The major ligand of the classic RAS, Angiotensin II (Ang II) acts predominantly 
      through the Ang II Type 1 receptor (AT1R), leading to vasoconstriction, 
      inflammation, and heightened oxidative stress. These processes can exacerbate 
      brain injuries. Ang II receptor blockers (ARBs) are AT1R antagonists. They have 
      been shown in several preclinical studies to enhance recovery from TBI in rodents 
      through improvements in molecular, cellular and behavioral correlates of injury. 
      ARBs are now under consideration for clinical trials in TBI. Several different 
      RAS peptides that signal through receptors distinct from the AT1R, are also 
      potential therapeutic targets for TBI. The counter regulatory RAS pathway has 
      actions that oppose those stimulated by AT1R signaling. This alternative pathway 
      has many beneficial effects on cells in the central nervous system, bringing 
      about vasodilation, and having anti-inflammatory and anti-oxidative stress 
      actions. Stimulation of this pathway also has potential therapeutic value for the 
      treatment of TBI. This comprehensive review will provide an overview of the 
      various components of the RAS, with a focus on their direct relevance to TBI 
      pathology. It will explore different therapeutic agents that modulate this system 
      and assess their potential efficacy in treating TBI patients.
CI  - (c) 2023. This is a U.S. Government work and not under copyright protection in the 
      US; foreign copyright protection may apply.
FAU - Villapol, Sonia
AU  - Villapol S
AD  - Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, USA.
FAU - Janatpour, Zachary C
AU  - Janatpour ZC
AD  - Department of Pharmacology and Molecular Therapeutics, Uniformed Services 
      University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
FAU - Affram, Kwame O
AU  - Affram KO
AD  - Department of Pharmacology and Molecular Therapeutics, Uniformed Services 
      University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
FAU - Symes, Aviva J
AU  - Symes AJ
AUID- ORCID: 0000-0003-2557-9939
AD  - Department of Pharmacology and Molecular Therapeutics, Uniformed Services 
      University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. 
      Aviva.symes@usuhs.edu.
LA  - eng
GR  - TP210132/Congressionally Directed Medical Research Programs/
PT  - Journal Article
PT  - Review
DEP - 20230927
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Humans
MH  - *Renin-Angiotensin System
MH  - Angiotensin Receptor Antagonists/pharmacology
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Angiotensin II/pharmacology
MH  - *Brain Injuries, Traumatic/drug therapy
PMC - PMC10684482
OTO - NOTNLM
OT  - Angiotensin
OT  - Brain
OT  - Injury
OT  - Mas receptor
OT  - Neurodegeneration
OT  - Therapeutics
EDAT- 2023/09/28 00:42
MHDA- 2023/11/30 06:44
PMCR- 2024/10/01
CRDT- 2023/09/27 23:40
PHST- 2023/08/31 00:00 [accepted]
PHST- 2024/10/01 00:00 [pmc-release]
PHST- 2023/11/30 06:44 [medline]
PHST- 2023/09/28 00:42 [pubmed]
PHST- 2023/09/27 23:40 [entrez]
AID - S1878-7479(23)01998-0 [pii]
AID - 1435 [pii]
AID - 10.1007/s13311-023-01435-8 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2023 Oct;20(6):1565-1591. doi: 10.1007/s13311-023-01435-8. 
      Epub 2023 Sep 27.