Acute inhalation of combustion smoke triggers neuroinflammation and persistent anxiety-like behavior in the mouse

Murat F. Gorgun, Ming Zhuo, Ib Danelo Cortez, Kelly Dineley, Ella Englander

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Context: Acute inhalation of combustion smoke triggers neurologic sequelae in survivors. Due to the challenges posed by heterogeneity of smoke exposures in humans, mechanistic links between acute smoke inhalation and neuropathologic sequelae have not been systematically investigated. Methods: Here, using mouse model of acute inhalation of combustion smoke, we studied longitudinal neurobehavioral manifestations of smoke exposures and molecular/cellular changes in the mouse brain. Results: Immunohistochemical analyses at eight months post-smoke, revealed hippocampal astrogliosis and microgliosis accompanied by reduced myelination. Elevated expression of proinflammatory cytokines was also detected. Longitudinal testing in different neurobehavioral paradigms in the course of post-smoke recovery, revealed lasting anxiety-like behavior. The examined paradigms included the open field exploration/anxiety testing at two, four and six months post-smoke, which detected decreases in total distance traveled and time spent in the central arena in the smoke-exposed compared to sham-control mice, suggestive of dampened exploratory activity and increased anxiety-like behavior. In agreement with reduced open field activity, cued fear conditioning test revealed increased freezing in response to conditioned auditory stimulus in mice after acute smoke inhalation. Similarly, elevated plus maze testing demonstrated lesser presence in open arms of the maze, consistent with anxiety-like behavior, for the post-smoke exposure mice. Conclusions: Taken together, our data demonstrate for the first time persistent neurobehavioral manifestations of acute inhalation of combustion smoke and provide new insights into long-term progression of events initiated by disrupted brain oxygenation that might contribute to lasting adverse sequelae in survivors of smoke inhalation injuries.

Original languageEnglish (US)
Pages (from-to)598-610
Number of pages13
JournalInhalation Toxicology
Volume29
Issue number12-14
DOIs
StatePublished - Dec 6 2017

Fingerprint

Smoke
Inhalation
Anxiety
Neurobehavioral Manifestations
Survivors
Smoke Inhalation Injury
Brain
Testing
Oxygenation
Nervous System
Freezing
Fear
Cytokines
Recovery

Keywords

  • anxiety-like behavior
  • brain
  • longitudinal behavioral testing
  • myelination
  • neuroinflammation
  • Smoke inhalation injury

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Acute inhalation of combustion smoke triggers neuroinflammation and persistent anxiety-like behavior in the mouse. / Gorgun, Murat F.; Zhuo, Ming; Cortez, Ib Danelo; Dineley, Kelly; Englander, Ella.

In: Inhalation Toxicology, Vol. 29, No. 12-14, 06.12.2017, p. 598-610.

Research output: Contribution to journalArticle

@article{c7799e32eb0c4ce696b4f3a419c285e7,
title = "Acute inhalation of combustion smoke triggers neuroinflammation and persistent anxiety-like behavior in the mouse",
abstract = "Context: Acute inhalation of combustion smoke triggers neurologic sequelae in survivors. Due to the challenges posed by heterogeneity of smoke exposures in humans, mechanistic links between acute smoke inhalation and neuropathologic sequelae have not been systematically investigated. Methods: Here, using mouse model of acute inhalation of combustion smoke, we studied longitudinal neurobehavioral manifestations of smoke exposures and molecular/cellular changes in the mouse brain. Results: Immunohistochemical analyses at eight months post-smoke, revealed hippocampal astrogliosis and microgliosis accompanied by reduced myelination. Elevated expression of proinflammatory cytokines was also detected. Longitudinal testing in different neurobehavioral paradigms in the course of post-smoke recovery, revealed lasting anxiety-like behavior. The examined paradigms included the open field exploration/anxiety testing at two, four and six months post-smoke, which detected decreases in total distance traveled and time spent in the central arena in the smoke-exposed compared to sham-control mice, suggestive of dampened exploratory activity and increased anxiety-like behavior. In agreement with reduced open field activity, cued fear conditioning test revealed increased freezing in response to conditioned auditory stimulus in mice after acute smoke inhalation. Similarly, elevated plus maze testing demonstrated lesser presence in open arms of the maze, consistent with anxiety-like behavior, for the post-smoke exposure mice. Conclusions: Taken together, our data demonstrate for the first time persistent neurobehavioral manifestations of acute inhalation of combustion smoke and provide new insights into long-term progression of events initiated by disrupted brain oxygenation that might contribute to lasting adverse sequelae in survivors of smoke inhalation injuries.",
keywords = "anxiety-like behavior, brain, longitudinal behavioral testing, myelination, neuroinflammation, Smoke inhalation injury",
author = "Gorgun, {Murat F.} and Ming Zhuo and Cortez, {Ib Danelo} and Kelly Dineley and Ella Englander",
year = "2017",
month = "12",
day = "6",
doi = "10.1080/08958378.2018.1432728",
language = "English (US)",
volume = "29",
pages = "598--610",
journal = "Inhalation Toxicology",
issn = "0895-8378",
publisher = "Informa Healthcare",
number = "12-14",

}

TY - JOUR

T1 - Acute inhalation of combustion smoke triggers neuroinflammation and persistent anxiety-like behavior in the mouse

AU - Gorgun, Murat F.

AU - Zhuo, Ming

AU - Cortez, Ib Danelo

AU - Dineley, Kelly

AU - Englander, Ella

PY - 2017/12/6

Y1 - 2017/12/6

N2 - Context: Acute inhalation of combustion smoke triggers neurologic sequelae in survivors. Due to the challenges posed by heterogeneity of smoke exposures in humans, mechanistic links between acute smoke inhalation and neuropathologic sequelae have not been systematically investigated. Methods: Here, using mouse model of acute inhalation of combustion smoke, we studied longitudinal neurobehavioral manifestations of smoke exposures and molecular/cellular changes in the mouse brain. Results: Immunohistochemical analyses at eight months post-smoke, revealed hippocampal astrogliosis and microgliosis accompanied by reduced myelination. Elevated expression of proinflammatory cytokines was also detected. Longitudinal testing in different neurobehavioral paradigms in the course of post-smoke recovery, revealed lasting anxiety-like behavior. The examined paradigms included the open field exploration/anxiety testing at two, four and six months post-smoke, which detected decreases in total distance traveled and time spent in the central arena in the smoke-exposed compared to sham-control mice, suggestive of dampened exploratory activity and increased anxiety-like behavior. In agreement with reduced open field activity, cued fear conditioning test revealed increased freezing in response to conditioned auditory stimulus in mice after acute smoke inhalation. Similarly, elevated plus maze testing demonstrated lesser presence in open arms of the maze, consistent with anxiety-like behavior, for the post-smoke exposure mice. Conclusions: Taken together, our data demonstrate for the first time persistent neurobehavioral manifestations of acute inhalation of combustion smoke and provide new insights into long-term progression of events initiated by disrupted brain oxygenation that might contribute to lasting adverse sequelae in survivors of smoke inhalation injuries.

AB - Context: Acute inhalation of combustion smoke triggers neurologic sequelae in survivors. Due to the challenges posed by heterogeneity of smoke exposures in humans, mechanistic links between acute smoke inhalation and neuropathologic sequelae have not been systematically investigated. Methods: Here, using mouse model of acute inhalation of combustion smoke, we studied longitudinal neurobehavioral manifestations of smoke exposures and molecular/cellular changes in the mouse brain. Results: Immunohistochemical analyses at eight months post-smoke, revealed hippocampal astrogliosis and microgliosis accompanied by reduced myelination. Elevated expression of proinflammatory cytokines was also detected. Longitudinal testing in different neurobehavioral paradigms in the course of post-smoke recovery, revealed lasting anxiety-like behavior. The examined paradigms included the open field exploration/anxiety testing at two, four and six months post-smoke, which detected decreases in total distance traveled and time spent in the central arena in the smoke-exposed compared to sham-control mice, suggestive of dampened exploratory activity and increased anxiety-like behavior. In agreement with reduced open field activity, cued fear conditioning test revealed increased freezing in response to conditioned auditory stimulus in mice after acute smoke inhalation. Similarly, elevated plus maze testing demonstrated lesser presence in open arms of the maze, consistent with anxiety-like behavior, for the post-smoke exposure mice. Conclusions: Taken together, our data demonstrate for the first time persistent neurobehavioral manifestations of acute inhalation of combustion smoke and provide new insights into long-term progression of events initiated by disrupted brain oxygenation that might contribute to lasting adverse sequelae in survivors of smoke inhalation injuries.

KW - anxiety-like behavior

KW - brain

KW - longitudinal behavioral testing

KW - myelination

KW - neuroinflammation

KW - Smoke inhalation injury

UR - http://www.scopus.com/inward/record.url?scp=85041636727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041636727&partnerID=8YFLogxK

U2 - 10.1080/08958378.2018.1432728

DO - 10.1080/08958378.2018.1432728

M3 - Article

VL - 29

SP - 598

EP - 610

JO - Inhalation Toxicology

JF - Inhalation Toxicology

SN - 0895-8378

IS - 12-14

ER -