Citation

Tweedie D, Rachmany L, Rubovitch V, Li Y, Holloway HW, Lehrmann E, Zhang Y, Becker KG, Perez E, Hoffer BJ, Pick CG, Greig NH. Alzheimers Dement. 2015; 12(1): 34-48.

Affiliation

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Copyright

(Copyright © 2015, Alzheimer's Association, Publisher Elsevier Publishing)

DOI

10.1016/j.jalz.2015.07.489

PMID

26327236

Abstract

BACKGROUND: Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently, there are no approved drugs for blast brain injury.

METHODS: Exendin-4 (Ex-4), administered subcutaneously, was evaluated as a pretreatment (48 hours) and postinjury treatment (2 hours) on neurodegeneration, behaviors, and gene expressions in a murine open field model of blast injury.

RESULTS: B-TBI induced neurodegeneration, changes in cognition, and genes expressions linked to dementia disorders. Ex-4, administered preinjury or postinjury, ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7-14, and attenuated genes regulated by blast at day 14 postinjury.

CONCLUSIONS: The present data suggest shared pathologic processes between concussive and B-TBI, with end points amenable to beneficial therapeutic manipulation by Ex-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiologic studies of Barnes et al. who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life.

Language: en