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

Zou YY, Yuan Y, Kan EM, Lu J, Ling EA - J Neuroinflammation (2014)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

ABSTRACT

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‚ÄČ+‚ÄČcells 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.

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TUNEL immunopositive cells in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer in the C group (A), the SI‚ÄČ+‚ÄČS group at 72 h (B), and the SI‚ÄČ+‚ÄČAG group at 72 h (C). Smoke inhalation increases the incidence of apoptotic cells (arrows) in the mitral cell layer (B) compared with the C group (A). The frequency of apoptotic cells in the olfactory bulb is significantly reduced in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with the SI‚ÄČ+‚ÄČS group (C). Scale bar =50 őľm. (D) Bar graphs show increase in apoptotic cells in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group. Apoptotic cells are significantly suppressed in numbers in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with SI‚ÄČ+‚ÄČS.
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Fig11: TUNEL immunopositive cells in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer in the C group (A), the SI‚ÄČ+‚ÄČS group at 72 h (B), and the SI‚ÄČ+‚ÄČAG group at 72 h (C). Smoke inhalation increases the incidence of apoptotic cells (arrows) in the mitral cell layer (B) compared with the C group (A). The frequency of apoptotic cells in the olfactory bulb is significantly reduced in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with the SI‚ÄČ+‚ÄČS group (C). Scale bar =50 őľm. (D) Bar graphs show increase in apoptotic cells in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group. Apoptotic cells are significantly suppressed in numbers in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with SI‚ÄČ+‚ÄČS.

Mentions: Smoke inhalation-induced apoptosis was observed in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer (Figure¬†11). The number of cells undergoing apoptosis as evidenced by TUNEL labeling was markedly increased (P <0.01) in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group (Figure¬†11A-D). In the SI‚ÄČ+‚ÄČAG group, the number of TUNEL-positive cells was reduced compared with those without drug treatment at 72 h, but the decrease was not statistically significant (Figure¬†11B-D).Figure 11


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

Zou YY, Yuan Y, Kan EM, Lu J, Ling EA - J Neuroinflammation (2014)

TUNEL immunopositive cells in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer in the C group (A), the SI‚ÄČ+‚ÄČS group at 72 h (B), and the SI‚ÄČ+‚ÄČAG group at 72 h (C). Smoke inhalation increases the incidence of apoptotic cells (arrows) in the mitral cell layer (B) compared with the C group (A). The frequency of apoptotic cells in the olfactory bulb is significantly reduced in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with the SI‚ÄČ+‚ÄČS group (C). Scale bar =50 őľm. (D) Bar graphs show increase in apoptotic cells in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group. Apoptotic cells are significantly suppressed in numbers in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with SI‚ÄČ+‚ÄČS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4197300&req=5

Fig11: TUNEL immunopositive cells in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer in the C group (A), the SI‚ÄČ+‚ÄČS group at 72 h (B), and the SI‚ÄČ+‚ÄČAG group at 72 h (C). Smoke inhalation increases the incidence of apoptotic cells (arrows) in the mitral cell layer (B) compared with the C group (A). The frequency of apoptotic cells in the olfactory bulb is significantly reduced in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with the SI‚ÄČ+‚ÄČS group (C). Scale bar =50 őľm. (D) Bar graphs show increase in apoptotic cells in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group. Apoptotic cells are significantly suppressed in numbers in the SI‚ÄČ+‚ÄČAG group at 72 h, as compared with SI‚ÄČ+‚ÄČS.
Mentions: Smoke inhalation-induced apoptosis was observed in the external plexiform layer, mitral cell layer, internal plexiform layer, and granule cell layer (Figure¬†11). The number of cells undergoing apoptosis as evidenced by TUNEL labeling was markedly increased (P <0.01) in the SI‚ÄČ+‚ÄČS group at 72 h, as compared with the C group (Figure¬†11A-D). In the SI‚ÄČ+‚ÄČAG group, the number of TUNEL-positive cells was reduced compared with those without drug treatment at 72 h, but the decrease was not statistically significant (Figure¬†11B-D).Figure 11

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

ABSTRACT

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‚ÄČ+‚ÄČcells 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.

Show MeSH
Related in: MedlinePlus