Bielanin, J.P.; Metwally, S.A.H.; Oft, H.C.; Paruchuri, S.S.; Lin, L.; Capuk, O.; Pennock, N.D.; Song, S.; Sun, D. NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment. Preprints2024, 2024041372. https://doi.org/10.20944/preprints202404.1372.v1
APA Style
Bielanin, J.P., Metwally, S.A.H., Oft, H.C., Paruchuri, S.S., Lin, L., Capuk, O., Pennock, N.D., Song, S., & Sun, D. (2024). NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment. Preprints. https://doi.org/10.20944/preprints202404.1372.v1
Chicago/Turabian Style
Bielanin, J.P., Shanshan Song and Dandan Sun. 2024 "NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment" Preprints. https://doi.org/10.20944/preprints202404.1372.v1
Abstract
Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.
Keywords
concussion; diffuse axonal injury; neuroinflammation; oxidative stress; white matter injury
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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