Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse
- 24 Downloads
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.
KeywordsNeuroglobin Neuroprotection Neuroinflammation Combustion smoke inhalation brain injury Neurogenesis Novel object recognition
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.
- 9.Azarov I, Wang L, Rose JJ, Xu Q, Huang XN, Belanger A, Wang Y, Guo L, Liu C, Ucer KB, McTiernan CF, O'Donnell CP, Shiva S, Tejero J, Kim-Shapiro DB, Gladwin MT (2016) Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning. Sci Transl Med 8:368ra173CrossRefGoogle Scholar
- 35.Dineley KT, Xia X, Bui D, Sweatt JD, Zheng H (2002) Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J Biol Chem 277:22768–22780CrossRefGoogle Scholar
- 39.Hernandez CM, Kayed R, Zheng H, Sweatt JD, Dineley KT (2010) Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease. J Neurosci 30:2442–2453CrossRefGoogle Scholar
- 59.Tsai CF, Yip PK, Chen SY, Lin JC, Yeh ZT, Kung LY, Wang CY, Fan YM (2014) The impacts of acute carbon monoxide poisoning on the brain: longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae. Clin Neurol Neurosurg 119:21–27CrossRefGoogle Scholar