Combustion smoke-induced inflammation in the olfactory bulb of adult rats

Journal of Neuroinflammation

Eng-Ang Ling³  Jia Lu³  Enci Mary Kan⁴  Yun Yuan²  Ying-Ying Zou¹ 

[1] Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming 650500, PR China;Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming 650500, PR China;Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117597, Singapore;Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore

关键词: smoke;    olfactory bulb;    nitric oxide synthase;    inflammation;    edema;   

Others  :  1150491
DOI  :  10.1186/s12974-014-0176-5

 received in 2014-08-12, accepted in 2014-09-29,  发布年份 2014

【 摘 要 】

Background

The damaging effect of combustion smoke inhalation on the lung is widely reported but information on its effects on the olfactory bulb is lacking. This study sought to determine the effects of smoke inhalation on the olfactory bulb, whose afferent input neurons in the nasal mucosa are directly exposed to external stimuli, such as smoke.

Methods

Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at different time points. Changes in olfactory bulb proteins including vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Na⁺-K⁺-Cl^? cotransporter 1 (NKCC1), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4) were evaluated by Western blot analysis. In addition, ELISA was conducted for cytokine and chemokine levels, and double immunofluorescence labeling was carried out for GFAP/VEGF, GFAP/AQP4, NeuN/nNOS, GFAP/NKCC1, NeuN/NKCC1, GFAP/Rhodamine isothiocyanate (RITC), and transferase dUTP nick end labeling (TUNEL). Aminoguanidine was administered to determine the effects of iNOS inhibition on the targets probed after smoke inhalation.

Results

The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation. Concurrent to this was a drastic increase in AQP4 expression and RITC permeability. Aminoguanidine administration decreased the expression of iNOS and RITC extravasation after smoke inhalation. This was coupled with a significant reduction in incidence of TUNEL?+?cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).

Conclusions

These findings suggest that the upregulation of iNOS in response to smoke inhalation plays a major role in the olfactory bulb inflammatory pathophysiology, along with a concomitant increase in pro-inflammatory molecules, vascular permeability, and edema. Overall, these findings indicate that the olfactory bulb is vulnerable to smoke inhalation.

【 授权许可】

   
2014 Zou et al.; licensee BioMed Central Ltd.

【 图 表 】

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