Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats
Part of the
Acta Neurochirurgica Supplement
book series (NEUROCHIRURGICA, volume 121)
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.
KeywordsCannabinoid receptor type 2 Subarachnoid hemorrhage Pulmonary edema Myeloperoxidase Junctional adhesion molecule
neurogenic pulmonary edema
Cannabinoid type 2 receptor
junctional adhesion molecule
early brain injury
analysis of variance.
This study is partially supported by National Institutes of Health grant NS081740 to JHZ.
Conflict of Interest
The authors declare no conflicts of interest.
Altay O, Suzuki H, Hasegawa Y, Caner B, Krafft PR, Fujii M, Tang J, Zhang JH (2012) Isoflurane attenuates blood–brain barrier disruption in ipsilateral hemisphere after subarachnoid hemorrhage in mice. Stroke 43:2513–2516PubMedCentralCrossRefPubMedGoogle Scholar
Brathwaite S, Macdonald RL (2014) Current management of delayed cerebral ischemia: update from results of recent clinical trials. Transl Stroke Res 5:207–226CrossRefPubMedGoogle Scholar
Bühler D, Schüller K, Plesnila N (2014) Protocol for the induction of subarachnoid hemorrhage in mice by perforation of the circle of Willis with an endovascular filament. Transl Stroke Res 5:653–659PubMedCentralCrossRefPubMedGoogle Scholar
Fujii M, Sherchan P, Krafft PR, Rolland WB, Soejima Y, Zhang JH (2014) Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats. J Neurol Sci 342:101–106PubMedCentralCrossRefPubMedGoogle Scholar
Fujii M, Sherchan P, Soejima Y, Hasegawa Y, Flores J, Doycheva D, Zhang JH (2014) Cannabinoid receptor type 2 agonist attenuates apoptosis by activation of phosphorylated CREB-Bcl-2 pathway after subarachnoid hemorrhage in rats. Exp Neurol 261:396–403CrossRefPubMedGoogle Scholar
Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH (2013) Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 4:432–446PubMedCentralCrossRefPubMedGoogle Scholar
Macmillan CS, Grant IS, Andrews PJ (2002) Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intensive Care Med 28:1012–1023CrossRefPubMedGoogle Scholar
Nourshargh S, Krombach F, Dejana E (2006) The role of JAM-A and PECAM-1 in modulating leukocyte infiltration in inflamed and ischemic tissues. J Leukoc Biol 80:714–718CrossRefPubMedGoogle Scholar
Piazza O, Venditto A, Tufano R (2011) Neurogenic pulmonary edema in subarachnoid hemorrhage. Panminerva Med 53:203–2101PubMedGoogle Scholar
Pluta RM, Bacher J, Skopets B, Hoffmann V (2014) A non-human primate model of aneurismal subarachnoid hemorrhage (SAH). Transl Stroke Res 5:681–691CrossRefPubMedGoogle Scholar
Rassler B, Reissig C, Briest W, Tannapfel A, Zimmer HG (2003) Pulmonary edema and pleural effusion in norepinephrine-stimulated rats–hemodynamic or inflammatory effect? Mol Cell Biochem 250:55–63CrossRefPubMedGoogle Scholar
Schievink WI, Wijdicks EF, Parisi JE, Piepgras DG, Whisnant JP (1995) Sudden death from aneurysmal subarachnoid hemorrhage. Neurology 45:871–874CrossRefPubMedGoogle Scholar
Sehba FA (2014) Rat endovascular perforation model. Transl Stroke Res 5:660–668CrossRefPubMedGoogle Scholar
Soini Y (2011) Claudins in lung diseases. Respir Res 12:70PubMedCentralCrossRefPubMedGoogle Scholar
Steinberg J, Halter J, Schiller H, Gatto L, Carney D, Lee HM, Golub L, Nieman G (2005) Chemically modified tetracycline prevents the development of septic shock and acute respiratory distress syndrome in a clinically applicable porcine model. Shock 24:348–356CrossRefPubMedGoogle Scholar
Tschöp J, Kasten KR, Nogueiras R, Goetzman HS, Cave CM, England LG, Dattilo J, Lentsch AB, Tschöp MH, Caldwell CC (2009) The cannabinoid receptor 2 is critical for the host response to sepsis. J Immunol 183:499–505PubMedCentralCrossRefPubMedGoogle Scholar
Weir BK (1978) Pulmonary edema following fatal aneurysm rupture. J Neurosurg 49:502–507CrossRefPubMedGoogle Scholar
© Springer International Publishing Switzerland 2016