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

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Brain Edema XVI

Part of the book series: Acta Neurochirurgica Supplement ((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.

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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.

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Acknowledgments

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

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The authors declare no conflicts of interest.

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Correspondence to John H. Zhang .

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Fujii, M., Sherchan, P., Soejima, Y., Doycheva, D., Zhao, D., Zhang, J.H. (2016). Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_24

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  • DOI: https://doi.org/10.1007/978-3-319-18497-5_24

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-18496-8

  • Online ISBN: 978-3-319-18497-5

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