Dexmedetomidine promotes the recovery of neurogenesis in aged mouse with postoperative cognitive dysfunction.

Recently, growing evidence has demonstrated Dexmedetomidine (Dex) a promising intervene preventing postoperative cognitive decline (POCD) following surgery, which is associated with neuroinflammation leading to neuronal apoptosis and deregulated neurogenesis. Previous studies suggested the anti-inflammation and anti-neuroapoptosis action of Dex. Therefore we hypothesize the promoting neurogenesis of Dex linked to stimulating BDNF and subsequent p-MPAK production in a rat model of POCD. In the present study, the POCD animal model was established by performing an exploratory laparotomy under isoflurane anaesthesia in old rats, utilizing which Dex response is confirmed by behavioural tests. Inflammatory biomarkers as IL-1β and TNF-α, mature neuron percentage measured by doublecortin staining (DCX), promoting factors as brain derived growth factor (BDNF), phosphorylated cAMP response element binding protein (CREB) and proteins of kinase A (PKA), MAPK production as p-P38-MAPK protein express were measured. Herein, we showed that surgery reduced DCX-positive neurons and expression of BDNF representing neurogenesis profoundly. As expected, Dex rescued the associated cognitive impairment and inflammatory changes, as well as up-regulated expression of BDNF, PKA, p-CREB/CREB and following p-P38-MAPK regulation. Our results confirmed the protective Dex response and indicated the proneurogenesis role of it as well, suggesting the mechanism of beneficial effects of Dex to prevent POCD.