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Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse

  • Murat F. Gorgun
  • Ming Zhuo
  • Kelly T. Dineley
  • Ella W. EnglanderEmail author
Original Paper
  • 30 Downloads

Abstract

Acute inhalation of combustion smoke produces long-term neurologic deficits in survivors. To study the mechanisms that contribute to the development of neurologic deficits and identify targets for prevention, we developed a mouse model of acute inhalation of combustion smoke, which supports longitudinal investigation of mechanisms that underlie the smoke induced inimical sequelae in the brain. Using a transgenic mouse engineered to overexpress neuroglobin, a neuroprotective oxygen-binding globin protein, we previously demonstrated that elevated neuroglobin preserves mitochondrial respiration and attenuates formation of oxidative DNA damage in the mouse brain after smoke exposure. In the current study, we show that elevated neuronal neuroglobin attenuates the persistent inflammatory changes induced by smoke exposure in the mouse brain and mitigates concordant smoke-induced long-term neurobehavioral deficits. Specifically, we found that increases in hippocampal density of GFAP and Iba-1 positive cells that are detected post-smoke in wild-type mice are absent in the neuroglobin overexpressing transgenic (Ngb-tg) mice. Similarly, the smoke induced hippocampal myelin depletion is not observed in the Ngb-tg mice. Importantly, elevated neuroglobin alleviates behavioral and memory deficits that develop after acute smoke inhalation in the wild-type mice. Taken together, our findings suggest that the protective effects exerted by neuroglobin in the brains of smoke exposed mice afford protection from long-term neurologic sequelae of acute inhalation of combustion smoke. Our transgenic mouse provides a tool for assessing the potential of elevated neuroglobin as possible strategy for management of smoke inhalation injury.

Keywords

Neuroglobin Neuroprotection Neuroinflammation Combustion smoke inhalation brain injury Neurogenesis Novel object recognition 

Notes

Funding

This work was supported by grants from Shriners Hospitals for Children (86700) and the National Institutes of Health (ES014613) to EWE.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Surgery, Medical BranchUniversity of TexasGalvestonUSA
  2. 2.Department of NeurologyUniversity of Texas Medical BranchGalvestonUSA
  3. 3.Mitchell Center for Neurodegenerative DiseasesUniversity of Texas Medical BranchGalvestonUSA
  4. 4.Center for Addiction ResearchUniversity of Texas Medical BranchGalvestonUSA
  5. 5.Shriners Hospitals for ChildrenGalvestonUSA

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