Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.
Alzheimers Dement, 2016/1;12(1):34-48.
Tweedie D[1], Rachmany L[2], Rubovitch V[2], Li Y[3], Holloway HW[3], Lehrmann E[4], Zhang Y[4], Becker KG[4], Perez E[5], Hoffer BJ[6], Pick CG[7], Greig NH[3]
Affiliations
PMID: 26327236
Impact factor: 16.655
Abstract
introduction: 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.
discussion: 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.
Keywords: Alzheimer's disease; Behavioral deficits; Blast injury; Exendin-4; Gene expression; Glucagon-like peptide-1; Neurodegeneration; Parkinson's disease; Traumatic brain injury
MeSH terms
Animals; Blast Injuries; Brain Concussion; Cognition; Cognition Disorders; Exenatide; Gene Expression; Glucagon-Like Peptide 1; Injections, Subcutaneous; Male; Mice; Mice, Inbred ICR; Neuroprotective Agents; Peptides; Venoms
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download