Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury

Ryan P. Bruhns, Maha Ibrahim Sulaiman, Michael Gaub, Esther H. Bae, Rachel B. Davidson Knapp, Anna R. Larson, Angela Smith, Deziree L. Coleman, William D. Staatz, Alexander J. Sandweiss, Bellal A Joseph, Meredith Hay, Tally M. Largent-Milnes, Todd W. Vanderah

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Traumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model. Materials and methods: Male mice (n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) (n = 12) or vehicle (n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1–5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury. Results: Administration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control. Discussion: These are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries.

Original languageEnglish (US)
Article number903980
JournalFrontiers in Behavioral Neuroscience
Volume16
DOIs
StatePublished - Aug 4 2022

Keywords

  • angiotensin 1-7
  • cognitive impairment
  • Mas receptor
  • pTau
  • traumatic brain injury

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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