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.
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.