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)


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.


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



neurogenic pulmonary edema


subarachnoid hemorrhage


Cannabinoid type 2 receptor




junctional adhesion molecule


early brain injury


intraperitoneal administration


tight junctions


phosphate-buffered saline


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.


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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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