Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

Abstract

Purpose:To investigate the role of the adenosine A 1 receptor in the rapid tolerance to cerebral ischemia induced by isoflurane preconditioning. Methods: Seventy-five rats were randomly assigned into five groups (n = 15 each): Control, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups. All animals underwent right middle cerebral artery occlusion (MCAO) for two hours. Isoflurane preconditioning was conducted one hour before MCAO in Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups by exposing the animals to 1.5% isoflurane in 98% oxygen for one hour. In the Control and DPCPX groups, animals were exposed to 98% oxygen one hour before MCAO for one hour. A selective adenosine A 1 receptor antagonist, DPCPX, was administered (0.1 mg·kg -1 ) 15 min before isoflurane/oxygen exposure in the DPCPX and DPCPX+Isoflurane groups to evaluate the effect of adenosine A 1 receptor antagonist on isoflurane preconditioning. Dimethyl sulfoxide, the solvent of DPCPX, was administered (1 mL·kg -1 ) 15 min before isoflurane exposure in the Vehicle+Isoflurane group. Neurological deficit scores and brain infarct volumes were evaluated 24 hr after reperfusion. Results: Animals in the Isoflurane and Vehicle+Isoflurane groups developed lower neurological deficit scores and smaller brain infarct volumes than the Control group (P < 0.01). Animals in the DPCPX+Isoflurane group developed higher neurological deficit scores and larger brain infarct volumes than the Isoflurane and Vehicle+Isoflurane groups (P < 0.01). Conclusion:The present study demonstrates that preconditioning with isoflurane reduces focal cerebral ischemic injury in rats, and the adenosine A 1 receptor antagonist (DPCPX) attenuates the neuroprotection induced by isoflurane preconditioning. Objectif

p38 Mitogen-Activated Protein Kinase Contributes to Adenosine A1Receptor-Mediated Synaptic Depression in Area CA1 of the Rat Hippocampus

“…Another form of ischemic preconditioning in the brain can be elicited by volatile anesthetics (Kapinya et al, 2002;Zhao and Zuo, 2004;Bickler et al, 2005;Gray et al, 2005), which requires the activation of A 1 receptors (Liu et al, 2006) and p38 MAPK (Zheng and Zuo, 2004). In the present study, we showed that the inhibitory actions of adenosine A 1 receptors, but not other inhibitory receptors such as GABA B receptors, were attenuated by p38 MAPK inhibitors.…”

The neuroprotective mechanism of brain ischemic preconditioning

“…Some unspecific and specific adenosine A1 receptor antagonists abolished the ischemic tolerance. Moreover, Liu et al also demonstrated that isoflurane-induced tolerance against focal cerebral ischemia in the rat middle cerebral artery occlusion (MCAO) model was attenuated by adenosine A1 receptor antagonists [23] .…”

A Central Role of Connexin 43 in Hypoxic Preconditioning

“…1-3). Because a large literature has shown previously that adenosine plays a central role in preconditioning (Nakamura et al, 2002;Liu et al, 2006b) and our in vitro analysis indicated that preconditioning was associated with a Cx43-dependent increase in adenosine (Fig. 6), we next tested the effect of the blood-brain barrier (BBB)-permeable adenosine A 1 receptor antagonist DPCPX during preconditioning.…”