salvinorin a administration after global cerebral hypoxiaischemia preserves cerebrovascular autoregulation via kappa opioid receptor in pigletssalvinorin a政府在全球脑hypoxiaischemia保护脑血管自动调整通过κ阿片受体在小猪.pdfVIP

Salvinorin A Administration after Global Cerebral Hypoxia/Ischemia Preserves Cerebrovascular Autoregulation via Kappa Opioid Receptor in Piglets 1,2 1 1 1 1 Zhenhong Wang , Nan Ma , John Riley , William M. Armstead *, Renyu Liu * 1 Department of Anesthesiology and Critical Care, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Anesthesiology, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China Abstract Background: Cerebral hypoxia/ischemia (HI) is not uncommon during the perinatal period. If occurring, it can result in severe neurologic disabilities that persist throughout life. Salvinorin A, a non-opioid Kappa opioid receptors (KOR) selective agonist, has the potential to address this devastating situation. We have demonstrated that salvinorin A administration before HI, preserves pial artery autoregulative function through both the KOR and extracellular signal-regulated kinases (ERK) pathways. In the present study, we tested the hypothesis that administration of salvinorin A after HI could preserve cerebral autoregulation via KOR and ERK pathway. Methodology/Principal Findings: The response of the pial artery to hypercapnia, hypotension and isoproterenol were monitored before and 1 hour after HI in piglets equipped with a cranial window. Four groups of drug administration were performed after HI. The control group had DMSO (1 ml/kg, i.v.) administrated immediately after HI. Two salvinorin A treated groups had salvinorin A (10 mg/kg, i.v.) administrated 0 and 30 min after HI, respectively. The 4th group had salvinorin A and the KOR antagonist norbinaltorphimine (Nor-BIN, 1 mM to