Activation of alpha-4 beta-2 nicotinic receptor against cardiopulmonary bypass surgery induced brain injury by regulating NLRP3 pathway

Abstract

Present report evaluates the role of alpha-4 beta-2 nicotinic receptor (α4β2 nAChRs) in the development of cardiopulmonary bypass (CPB) surgery induced brain injury. Brain injury was induced by CPB and animals were treated with α4β2 nAChRs agonist (DHβE 9 mg/kg, s.c.) and α4β2 nAChRs antagonist (MLA 10 mg/kg, i.p.) 3 hr before the induction of CPB in the separate groups. Effect of α4β2 nAChRs agonist was determined on the neurological function in CPB induced brain injured rats. Level of cytokines, ROS and expression of NLRP3, ZO-1 and Occluding proteins were estimated in CPB induced brain injured rats. Effect of α4β2 nAChRs agonist was determined on the neuronal apoptosis and histopathological changes in the brain tissue. Result of the study suggest that neurological score was reversed in α4β2 nAChRs agonist treated group than CPB group. Level of cytokines and ROS was reduced in α4β2 nAChRs agonist treated group than CPB group. Neuronal apoptosis in α4β2 nAChRs agonist treated group was found to be reduced compared to CPB group of rats. Moreover Activation of α4β2 nAChRs ameliorates the altered expression of NLRP3, ZO-1 and Occluding protein in the brain tissue of CPB induced brain injured rats. In conclusion, Data of report suggest that treatment with α4β2 nAChRs agonist protects the brain injury in cardiopulmonary bypass surgery induced brain injury by regulating NLRP3 pathway.