Raquel Rodríguez-González1, Tomás Sobrino2, Sonia Veiga3, Pablo López4, Javier Rodríguez-García5, Sonia Veiras del Río6, Aurora Baluja7, José Castillo8, Julián Álvarez9. 1. Department of Nursing, CLINURSID Research group, School of Nursing, University of Santiago de Compostela, Santiago de Compostela, Spain; Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: raquel_rg82@yahoo.es. 2. Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: tomas.sobrino.moreiras@sergas.es. 3. Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: svsans@gmail.com. 4. Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: pabblolp@hotmail.com. 5. Department of Biochemistry, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: javier.rodriguez.garcia@sergas.es. 6. Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: veiras1@gmail.com. 7. Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: mariauror@gmail.com. 8. Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: jose.castillo@usc.es. 9. Department of Anesthesiology, Critical Care and Pain Management, Critical Patient Translational Research Group, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: julian.alvarez.escudero@sergas.es.
Abstract
AIMS: Dexmedetomidine is a selective agonist of α2-adrenergic receptors with clinical anesthetic and analgesic properties that has also shown neuroprotective effects on several models of brain injury. Because perioperative stroke and brain damage are frequent causes of death in critical care units, we aimed to investigate neuroprotective properties of dexmedetomidine using an in vitro model of cerebral ischemia. MAIN METHODS: Primary mixed rat brain cortical cultures were subjected to oxygen and glucose deprivation and treated with different doses of dexmedetomidine in order to analyze three conditioning strategies: preconditioning, intraconditioning and postconditioning. KEY FINDINGS: All dexmedetomidine pre-, intra- and postconditioning treatments showed neuroprotective effects reducing brain cell necrosis, although only preconditioning showed antiapoptotic effects. Dexmedetomidine treatments also reduced IL-6 and TNF-α levels, especially in the preconditioning groups. Oxidative stress was attenuated with all dexmedetomidine preconditioning treatments, but only with the higher dose in the intraconditioning group, and no effects were observed in the postconditioning. All conditioning strategies increased BDNF levels. SIGNIFICANCE: Dexmedetomidine-mediated neuroprotective effects in an in vitro model of cerebral ischemia involve the attenuation of inflammation and oxidative stress and the increment of BDNF expression.
AIMS: Dexmedetomidine is a selective agonist of α2-adrenergic receptors with clinical anesthetic and analgesic properties that has also shown neuroprotective effects on several models of brain injury. Because perioperative stroke and brain damage are frequent causes of death in critical care units, we aimed to investigate neuroprotective properties of dexmedetomidine using an in vitro model of cerebral ischemia. MAIN METHODS: Primary mixed rat brain cortical cultures were subjected to oxygen and glucose deprivation and treated with different doses of dexmedetomidine in order to analyze three conditioning strategies: preconditioning, intraconditioning and postconditioning. KEY FINDINGS: All dexmedetomidine pre-, intra- and postconditioning treatments showed neuroprotective effects reducing brain cell necrosis, although only preconditioning showed antiapoptotic effects. Dexmedetomidine treatments also reduced IL-6 and TNF-α levels, especially in the preconditioning groups. Oxidative stress was attenuated with all dexmedetomidine preconditioning treatments, but only with the higher dose in the intraconditioning group, and no effects were observed in the postconditioning. All conditioning strategies increased BDNF levels. SIGNIFICANCE: Dexmedetomidine-mediated neuroprotective effects in an in vitro model of cerebral ischemia involve the attenuation of inflammation and oxidative stress and the increment of BDNF expression.