Blast traumatic brain injury induced cognitive deficits are attenuated by pre- or post-injury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4 [Day 3 dataset]

Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently there are no approved drugs for blast brain injury. Exendin-4, administered subcutaneously, was evaluated as a pre-treatment (48 hours) and post-injury treatment (2 hours) on neurodegeneration, behaviors and gene expressions in a murine open field model of blast injury. B-TBI induced neurodegeneration, changes in cognition and genes expressions linked to dementia disorders. Exendin-4, administered pre- or post-injury ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7-14 and attenuated genes regulated by blast at day 14 post-injury. The present data suggest shared pathological processes between concussive and B-TBI, with endpoints amenable to beneficial therapeutic manipulation by exendin-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiological studies of Barnes and co-workers who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life.

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Tweedie D, Rachmany L, Rubovitch V, Li Y, Holloway HW, Lehrmann E, Zhang Y, Becker KG, Perez E, Hoffer BJ, Pick CG, Greig NH