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Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats

  • Mutsumi Fujii
  • Prativa Sherchan
  • Yoshiteru Soejima
  • Desislava Doycheva
  • Diana Zhao
  • John H. ZhangEmail author
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 121)

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.

Keywords

Cannabinoid receptor type 2 Subarachnoid hemorrhage Pulmonary edema Myeloperoxidase Junctional adhesion molecule 

Abbreviations

NPE

neurogenic pulmonary edema

SAH

subarachnoid hemorrhage

CB2R

Cannabinoid type 2 receptor

MPO

myeloperoxidase

JAM

junctional adhesion molecule

EBI

early brain injury

IP

intraperitoneal administration

TJs

tight junctions

PBS

phosphate-buffered saline

ANOVA

analysis of variance.

Notes

Acknowledgments

This study is partially supported by National Institutes of Health grant NS081740 to JHZ.

Conflict of Interest

The authors declare no conflicts of interest.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Mutsumi Fujii
    • 1
    • 2
  • Prativa Sherchan
    • 1
  • Yoshiteru Soejima
    • 1
  • Desislava Doycheva
    • 1
  • Diana Zhao
    • 1
  • John H. Zhang
    • 3
    Email author
  1. 1.Department of PhysiologyLoma Linda UniversityLoma LindaUSA
  2. 2.Department of NeurosurgeryTsuchiura Kyodo General HospitalIbarakiJapan
  3. 3.Department of Physiology, Neurosurgery, and AnesthesiologyLoma Linda UniversityLoma LindaUSA

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