Administration of Angiotensin-(1-7) daily for 5 days post-mTBI significantly improved cognitive function and reduced neuronal loss compared to saline control.
Does Angiotensin-(1-7) improve cognitive function and reduce neuroinflammation in a murine model of mild traumatic brain injury?
Sustained administration of Ang-(1-7) following mild traumatic brain injury in mice significantly improves neurologic outcomes and reduces neuroinflammation, suggesting a potential therapeutic modality for TBI.
p-value: p=<0.05
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.
Bruhns et al. (Thu,) conducted a other in Mild traumatic brain injury (mTBI) (n=108). Angiotensin-(1-7) vs. Normal saline (0.9%, i.p.) was evaluated on Cognitive function (Novel Object Recognition Discrimination Index) (p=<0.05). Administration of Angiotensin-(1-7) daily for 5 days post-mTBI significantly improved cognitive function and reduced neuronal loss compared to saline control.