Background: Postoperative cognitive dysfunction (POCD) is a common complication observed after surgery in elderly and is tighly associated with increased morbidity and mortality. The main physiopathological hypothesis underlying is based on the occurrence of postoperative neuroinflammation. In this context, we identified apelin, peptide with anti-inflammatory and neuroprotective activities as a potential therapeutic strategy to conteract POCD.
Materials and Methods: Surgery consisted of a closed tibia fracture of the right paw with intramedullary fixation under general anesthesia with sevoflurane (6%) and sufentanil (0,15ug). Experiments were conducted using 22 months C57Bl6/j male mice. Memory was assessed using a fear conditioning protocol (FC). Protocol was carried out into three steps : first a learning phase with FC, second surgery 1 hour after, third at day 3 the postoperative memory test with mesure of freezing rate. POCD was objectified in the case of reduction in freezing rate. Treatment consisted of a daily intraperitoneal injection of 0.015 μmol/day of apelin or same volume of 9 ‰ NaCl. First injection occurred 1 hour before surgery. At day 3, mice were sacrifed. Inflammation was mesured in blood and hippocampe using IL6 rt-PCR. Five groups of mice were performed : control with NaCl treatment (CN), control with apelin treatment (CA), surgery with NaCl treatment (SN), surgery with apelin treatement (SA), and a general anesthesia without fracture or treatment (GA). Data were subjected to an ANOVA statistical test. 
Results and Discussion: Only surgery induced POCD, SN mice had a significantly reduced freezing rate compared to CN mice (35% vs 57%, p< 0.05). Apelin did not improved memory capacities, freezing was similar in CN and CA mice (57% vs 62%,NS). Apelin warned POCD, level of freezing was similar in CN and SA (57% vs 65%,NS) or CA and SA (62% vs 65%,NS). At day 3, apelin reduced IL6-inflammation in blood and hippocamp.

Apelin: new treatment for postoperative cognitives dysfunction?