Background: Previous clinical studies have shown that emergence from isoflurane anaesthesia takes longer in elderly patients compared with middle-aged patients. The current study investigated whether delayed emergence from anaesthesia in older age is associated with the age-related decrease in orexin receptors by using a rat model. Methods: Adult and aged SpragueeDawley rats were used to assess the time to emergence after 30 min isoflurane anaesthesia (1.4 vol%), and differences in the orexinergic systems, including the number of orexinergic neurones, plasma orexin concentrations, and expression of orexin-1 (OX1R) and orexin-2 receptors, compared using immunofluorescence, radioimmunoassay, western blot, and real-time polymerase chain reaction. The effects of OX1R expression on emergence time were determined by virus-mediated overexpression of OX1R using intra-cerebroventricular injection. Results: The median (range) emergence time of aged rats was longer than that in adult rats [1082 (1010e1130) compared with 848 (829e938) s; P¼0.0009]. Plasma orexin concentrations were higher in the aged group than the adult group [34 (33e37) and 25 (22e31) pg ml À1 , respectively; P¼0.04], but the number of orexinergic neurones was similar in both groups. Protein expression of OX1R was lower in the aged group compared with the adult group [0.47 (0.35e0.58) compared with 0.97 (0.86e1.32), respectively; P¼0.002]. Overexpression of OX1R significantly shortened the emergence time in aged rats from [1120 (1040e1190) s] to [769 (576e928) s; P¼0.03]. Conclusions: Age-related decrease in OX1R expression is associated with delayed emergence from isoflurane anaesthesia in aged rats.

These results showed that mild hypothermia partially protects immature hippocampal neurons against OGD injury in part by interfering with the PAR signaling pathway.