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Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse.
Neurochem Res 2019; 44(9):2170-2181NR

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.

Authors+Show Affiliations

Department of Surgery, Medical Branch, University of Texas, 301 University Boulevard, Galveston, TX, 77555, USA.Department of Surgery, Medical Branch, University of Texas, 301 University Boulevard, Galveston, TX, 77555, USA.Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA. Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA. Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, USA.Department of Surgery, Medical Branch, University of Texas, 301 University Boulevard, Galveston, TX, 77555, USA. elenglan@utmb.edu. Shriners Hospitals for Children, Galveston, TX, USA. elenglan@utmb.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31420834

Citation

Gorgun, Murat F., et al. "Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced By Acute Inhalation of Combustion Smoke in the Mouse." Neurochemical Research, vol. 44, no. 9, 2019, pp. 2170-2181.
Gorgun MF, Zhuo M, Dineley KT, et al. Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse. Neurochem Res. 2019;44(9):2170-2181.
Gorgun, M. F., Zhuo, M., Dineley, K. T., & Englander, E. W. (2019). Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse. Neurochemical Research, 44(9), pp. 2170-2181. doi:10.1007/s11064-019-02856-8.
Gorgun MF, et al. Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced By Acute Inhalation of Combustion Smoke in the Mouse. Neurochem Res. 2019;44(9):2170-2181. PubMed PMID: 31420834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse. AU - Gorgun,Murat F, AU - Zhuo,Ming, AU - Dineley,Kelly T, AU - Englander,Ella W, Y1 - 2019/08/16/ PY - 2019/05/23/received PY - 2019/08/05/accepted PY - 2019/07/03/revised PY - 2019/8/20/pubmed PY - 2019/8/20/medline PY - 2019/8/18/entrez KW - Combustion smoke inhalation brain injury KW - Neurogenesis KW - Neuroglobin KW - Neuroinflammation KW - Neuroprotection KW - Novel object recognition SP - 2170 EP - 2181 JF - Neurochemical research JO - Neurochem. Res. VL - 44 IS - 9 N2 - 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. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/31420834/Elevated_Neuroglobin_Lessens_Neuroinflammation_and_Alleviates_Neurobehavioral_Deficits_Induced_by_Acute_Inhalation_of_Combustion_Smoke_in_the_Mouse L2 - https://doi.org/10.1007/s11064-019-02856-8 DB - PRIME DP - Unbound Medicine ER -