Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology

Cynthia S. Samary, Alane B. Ramos, Lígia A. Maia, Nazareth N. Rocha, Cíntia L. Santos, Raquel F. Magalhães, Amanda L. Clevelario, Pedro M. Pimentel-Coelho, Rosália Mendez-Otero, Fernanda F. Cruz, Vera L. Capelozzi, Tatiana P.T. Ferreira, Thea Koch, Marcelo Gama De Abreu, Claudia C. Dos Santos, Paolo Pelosi, Pedro L. Silva, Patricia R.M. Rocco

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.

Original languageEnglish
Article number249
JournalCritical Care
Volume22
Issue number1
DOIs
Publication statusPublished - Oct 5 2018

Fingerprint

Alveolar Macrophages
Lung Injury
Hematology
Stroke
Medicine
Health
Lung
Bronchoalveolar Lavage Fluid
Interleukin-6
Pneumonia
Tumor Necrosis Factor-alpha
Alveolar Epithelial Cells
Endothelial Cells
Macrophages
Brain
Aptitude
Tidal Volume
Pulmonary Edema
Encephalitis
Respiratory Rate

Keywords

  • Brain-lung interaction
  • Focal ischemic stroke
  • Inflammation
  • Lung injury
  • Macrophages

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology. / Samary, Cynthia S.; Ramos, Alane B.; Maia, Lígia A.; Rocha, Nazareth N.; Santos, Cíntia L.; Magalhães, Raquel F.; Clevelario, Amanda L.; Pimentel-Coelho, Pedro M.; Mendez-Otero, Rosália; Cruz, Fernanda F.; Capelozzi, Vera L.; Ferreira, Tatiana P.T.; Koch, Thea; De Abreu, Marcelo Gama; Dos Santos, Claudia C.; Pelosi, Paolo; Silva, Pedro L.; Rocco, Patricia R.M.

In: Critical Care, Vol. 22, No. 1, 249, 05.10.2018.

Research output: Contribution to journalArticle

Samary, CS, Ramos, AB, Maia, LA, Rocha, NN, Santos, CL, Magalhães, RF, Clevelario, AL, Pimentel-Coelho, PM, Mendez-Otero, R, Cruz, FF, Capelozzi, VL, Ferreira, TPT, Koch, T, De Abreu, MG, Dos Santos, CC, Pelosi, P, Silva, PL & Rocco, PRM 2018, 'Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology', Critical Care, vol. 22, no. 1, 249. https://doi.org/10.1186/s13054-018-2164-0
Samary, Cynthia S. ; Ramos, Alane B. ; Maia, Lígia A. ; Rocha, Nazareth N. ; Santos, Cíntia L. ; Magalhães, Raquel F. ; Clevelario, Amanda L. ; Pimentel-Coelho, Pedro M. ; Mendez-Otero, Rosália ; Cruz, Fernanda F. ; Capelozzi, Vera L. ; Ferreira, Tatiana P.T. ; Koch, Thea ; De Abreu, Marcelo Gama ; Dos Santos, Claudia C. ; Pelosi, Paolo ; Silva, Pedro L. ; Rocco, Patricia R.M. / Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology. In: Critical Care. 2018 ; Vol. 22, No. 1.
@article{484fee264a3d46cda23626d8b1a3f98f,
title = "Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology",
abstract = "Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from na{\"i}ve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from na{\"i}ve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.",
keywords = "Brain-lung interaction, Focal ischemic stroke, Inflammation, Lung injury, Macrophages",
author = "Samary, {Cynthia S.} and Ramos, {Alane B.} and Maia, {L{\'i}gia A.} and Rocha, {Nazareth N.} and Santos, {C{\'i}ntia L.} and Magalh{\~a}es, {Raquel F.} and Clevelario, {Amanda L.} and Pimentel-Coelho, {Pedro M.} and Ros{\'a}lia Mendez-Otero and Cruz, {Fernanda F.} and Capelozzi, {Vera L.} and Ferreira, {Tatiana P.T.} and Thea Koch and {De Abreu}, {Marcelo Gama} and {Dos Santos}, {Claudia C.} and Paolo Pelosi and Silva, {Pedro L.} and Rocco, {Patricia R.M.}",
year = "2018",
month = "10",
day = "5",
doi = "10.1186/s13054-018-2164-0",
language = "English",
volume = "22",
journal = "Critical Care",
issn = "1466-609X",
publisher = "Springer Science + Business Media",
number = "1",

}

TY - JOUR

T1 - Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology

AU - Samary, Cynthia S.

AU - Ramos, Alane B.

AU - Maia, Lígia A.

AU - Rocha, Nazareth N.

AU - Santos, Cíntia L.

AU - Magalhães, Raquel F.

AU - Clevelario, Amanda L.

AU - Pimentel-Coelho, Pedro M.

AU - Mendez-Otero, Rosália

AU - Cruz, Fernanda F.

AU - Capelozzi, Vera L.

AU - Ferreira, Tatiana P.T.

AU - Koch, Thea

AU - De Abreu, Marcelo Gama

AU - Dos Santos, Claudia C.

AU - Pelosi, Paolo

AU - Silva, Pedro L.

AU - Rocco, Patricia R.M.

PY - 2018/10/5

Y1 - 2018/10/5

N2 - Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.

AB - Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.

KW - Brain-lung interaction

KW - Focal ischemic stroke

KW - Inflammation

KW - Lung injury

KW - Macrophages

UR - http://www.scopus.com/inward/record.url?scp=85054461257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054461257&partnerID=8YFLogxK

U2 - 10.1186/s13054-018-2164-0

DO - 10.1186/s13054-018-2164-0

M3 - Article

VL - 22

JO - Critical Care

JF - Critical Care

SN - 1466-609X

IS - 1

M1 - 249

ER -