The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling

Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.