Research articleThe neuroprotective effect of apelin-13 in a mouse model of intracerebral hemorrhage

•Apelin-13 significantly improved motor function after ICH.•Apelin-13 can mitigate brain edema and inhibit apoptosis after ICH.•Apelin-13 is a promising agent in the therapy for ICH.

Adipocytokine apelin-13 is a peptide which could reportedly protect the brain against ischemic reperfusion injury and traumatic brain injury (TBI). Whether apelin-13 has any roles to play in intracerebral hemorrhage (ICH) has not been clarified. We aimed to investigate the roles of apelin-13 in ICH and effects on ICH-induced apoptosis. Firstly, CD-1 mice were subjected to infusion of Type IV collagenase (to induce ICH) or saline (for shams) into the left striatum. ICH animals received intracerebroventricular administration of vehicle, apelin-13 (50 μg dissolved in 5 μl saline) immediately after ICH. The motor function and the cerebral water content (CWC) as well as blood brain barrier (BBB) disruption were measured, coupled with determination of ICH-induced neural cell death by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). The apoptosis-associated proteins caspase-3 and Bcl-2 as well as the brain edema-associated proteins aquaporin-4 (AQP4) and MMP-9 were all assessed with western blotting. The results showed that apelin-13 decreased CWC and reduced Evans blue leakage into injured hemispheres, with the motor function significantly improved. Additionally, apelin-13 also acutely decreased the number of ICH-induced TUNEL-positive (TUNEL+) cells at 48 h after ICH. The expressions of AQP4, MMP-9, caspse-3 and Bcl-2 were all downregulated by apelin-13 at 24 h and 48 h after ICH. All these results revealed that apelin-13 attenuated brain edema and reduced cellular death by suppressing apoptosis after ICH in mice.

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