title: Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats.
abstract: We evaluated whether JWH133, a selective cannabinoid type 2 receptor (CB2R) agonist, prevented neurogenic pulmonary edema (NPE) after subarachnoid hemorrhage (SAH) by attenuating inflammation. Adult male rats were assigned to six groups: sham-operated, SAH with vehicle, SAH with JWH133 (0.3, 1.0, or 3.0 mg/kg) treatment 1 h after surgery, and SAH with JWH133 (1.0 mg/kg) at 1 h with a selective CB2R antagonist, SR144528 (3.0 mg/kg). The perforation model of SAH was performed and pulmonary wet-to-dry weight ratio was evaluated 24 and 72 h after surgery. Western blot analyses and immunohistochemistry were evaluated 24 h after surgery. JWH133 (1.0 mg/kg) significantly and most strongly improved lung edema 24 h after SAH. SR144528 administration significantly reversed the effects of JWH133 (1.0 mg/kg). SAH-induced increasing levels of myeloperoxidase (MPO) and decreasing levels of a tight junction (TJ) protein, junctional adhesion molecule (JAM)-A, were ameliorated by JWH133 (1.0 mg/kg) administration 24 h after SAH. Immunohistochemical assessment also confirmed substantial leukocyte infiltration in the outside of vessels in SAH, which were attenuated by JWH133 (1.0 mg/kg) injection. CB2R agonist ameliorated lung permeability by inhibiting leukocyte trafficking and protecting tight junction proteins in the lung of NPE after SAH.
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, CA, USA.|Department of Neurosurgery, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Prativa
authors.initials: P
authors.lastname: Sherchan
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Desislava
authors.initials: D
authors.lastname: Doycheva
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Neurosurgery, and Anesthesiology, Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, CA, 92354, USA. johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D062726:Junctional Adhesion Molecules / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*
chemical_list: D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D062726:Junctional Adhesion Molecules; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D009195:Peroxidase; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
keywords: Cannabinoid receptor type 2; Junctional adhesion molecule; Myeloperoxidase; Pulmonary edema; Subarachnoid hemorrhage