Open AccessCannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia–Ischemia
Author(s) -
Daniel Alonso-Alconada,
Francisco J. Álvarez,
Felipe GoñideCerio,
Enrique Hilario,
Antonia Álvarez
Publication year - 2020
Publication title -
international journal of molecular sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.455
H-Index - 162
eISSN - 1661-6596
pISSN - 1422-0067
DOI - 10.3390/ijms21041283
Subject(s) - oxidative stress , neuroinflammation , hypoxia (environmental) , medicine , cannabinoid , hypothermia , cannabinoid receptor , endocannabinoid system , cytokine , encephalopathy , inflammation , pharmacology , ischemia , asphyxia , tumor necrosis factor alpha , endocrinology , agonist , immunology , anesthesia , receptor , chemistry , oxygen , organic chemistry
In the process of neonatal encephalopathy, oxidative stress and neuroinflammation have a prominent role after perinatal asphyxia. With the exception of therapeutic hypothermia, no therapeutic interventions are available in the clinical setting to target either the oxidative stress or inflammation, despite the high prevalence of neurological sequelae of this devastating condition. The endocannabinoid system (ECS), recently recognized as a widespread neuromodulatory system, plays an important role in the development of the central nervous system (CNS). This study aims to evaluate the potential effect of the cannabinoid (CB) agonist WIN 55,212-2 (WIN) on reactive oxygen species (ROS) and early inflammatory cytokine production after hypoxia-ischemia (HI) in fetal lambs. Hypoxic-ischemic animals were subjected to 60 min of HI by partial occlusion of the umbilical cord. A group of lambs received a single dose of 0.01 μg/kg WIN, whereas non-asphyctic animals served as controls. WIN reduced the widespread and notorious increase in inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 induced by HI, a modulatory effect not observed for oxidative stress. Our study suggests that treatment with a low dose of WIN can alter the profile of pro-inflammatory cytokines 3 h after HI.