Apelin-13 attenuates early brain injury following subarachnoid hemorrhage via suppressing neuronal apoptosis through the GLP-1R/PI3K/Akt signaling.

Apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, possesses anti-apoptotic and neuroprotective properties. It has been shown to be a protective factor for different types of central nervous system insults, such as ischemia and traumatic brain injury. Here, we investigated the effects of apelin-13 on early brain injury (EBI) following subarachnoid hemorrhage (SAH), and the underlying molecular mechanisms involved. Apelin-13 was delivered to rats via intracerebroventricular administration. Neurological scores, brain water content and neuronal apoptosis were measured 24 h after SAH. The PI3K/Akt inhibitor LY294002 or GLP-1R siRNA were injected into the lateral cerebral ventricle before induction of SAH. Changes in the expression of p-Akt, GLP-1R and apoptosis-associated proteins (Bax, Bcl-2, cleaved caspase-3) were then investigated. Results showed that the levels of GLP-1R in neurons increased significantly, reaching a peak at 24 h after the induction of SAH. Treatment with apelin-13 improved neurological deficits, as well as alleviated brain edema and apoptotic cell death. Apelin-13 was also able to increase the levels of p-Akt, GLP-1R and Bcl-2, while inhibiting the expression levels of Bax and cleaved caspase-3. The anti-apoptotic and neuroprotective effects of apelin-13 were partially reversed by addition of LY294002 or GLP-1R siRNA. These results provide evidence that apelin-13 attenuates EBI following SAH via suppressing neuronal apoptosis, and that this effect may act partially via the activation of the GLP-1R/PI3K/Akt signaling pathway.