title: Adrenergic activation attenuates astrocyte swelling induced by hypotonicity and neurotrauma.
abstract: Edema in the central nervous system can rapidly result in life-threatening complications. Vasogenic edema is clinically manageable, but there is no established medical treatment for cytotoxic edema, which affects astrocytes and is a primary trigger of acute post-traumatic neuronal death. To test the hypothesis that adrenergic receptor agonists, including the stress stimulus epinephrine protects neural parenchyma from damage, we characterized its effects on hypotonicity-induced cellular edema in cortical astrocytes by in vivo and in vitro imaging. After epinephrine administration, hypotonicity-induced swelling of astrocytes was markedly reduced and cytosolic 3'-5'-cyclic adenosine monophosphate (cAMP) was increased, as shown by a fluorescence resonance energy transfer nanosensor. Although, the kinetics of epinephrine-induced cAMP signaling was slowed in primary cortical astrocytes exposed to hypotonicity, the swelling reduction by epinephrine was associated with an attenuated hypotonicity-induced cytosolic Ca(2+) excitability, which may be the key to prevent astrocyte swelling. Furthermore, in a rat model of spinal cord injury, epinephrine applied locally markedly reduced neural edema around the contusion epicenter. These findings reveal new targets for the treatment of cellular edema in the central nervous system.
authors.affiliation: Celica, BIOMEDICAL, Tehnološki park 24, Ljubljana, 1000, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, 1000, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Vardjan
authors.affiliation: Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, 1000, Slovenia.
authors.forename: Anemari
authors.initials: A
authors.lastname: Horvat
authors.affiliation: Departments of Neurosurgery and Physical Medicine & Rehabilitation, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Anderson
authors.affiliation: Departments of Neurosurgery and Physical Medicine & Rehabilitation, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dou
authors.initials: D
authors.lastname: Yu
authors.affiliation: Brain and Behaviour Discovery Institute, Medical College of Georgia, Augusta, Georgia.|Department of Neurosurgery, Medical College of Georgia, Augusta, Georgia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Croom
authors.affiliation: Departments of Neurosurgery and Physical Medicine & Rehabilitation, Harvard Medical School, Boston, Massachusetts.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, 1000, Slovenia.
authors.forename: Zala
authors.initials: Z
authors.lastname: Lužnik
authors.affiliation: Celica, BIOMEDICAL, Tehnološki park 24, Ljubljana, 1000, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, 1000, Slovenia.|Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, Ljubljana, 1000, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Kreft
authors.affiliation: Departments of Neurosurgery and Physical Medicine & Rehabilitation, Harvard Medical School, Boston, Massachusetts.|Division of SCI Research, VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Yang D
authors.initials: YD
authors.lastname: Teng
authors.affiliation: Brain and Behaviour Discovery Institute, Medical College of Georgia, Augusta, Georgia.|Department of Neurosurgery, Medical College of Georgia, Augusta, Georgia.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kirov
authors.affiliation: Celica, BIOMEDICAL, Tehnološki park 24, Ljubljana, 1000, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, 1000, Slovenia.
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051381:Rats; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D018663:Adrenergic Agents
keywords: astrocytes; cerebral cortex; contusion trauma; cytotoxic edema; epinephrine; spinal cord