Blast traumatic brain injury–induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon‐like peptide‐1 receptor agonist, exendin‐4. Issue 1 (29th August 2015)

• Record Type: Journal Article
• Authors: Tweedie, David; Rachmany, Lital; Rubovitch, Vardit; Li, Yazhou; Holloway, Harold W.; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G.; Perez, Evelyn; Hoffer, Barry J.; Pick, Chaim G.; Greig, Nigel H.
• Is Part Of: Alzheimer's & dementia. Volume 12:Issue 1(2016)
• Page Start: 34
• Page End: 48
• Publication Date: 2015-08-29
• Subjects: Exendin‐4 -- Blast injury -- Traumatic brain injury -- Neurodegeneration -- Alzheimer's disease -- Parkinson's disease -- Behavioral deficits -- Gene expression -- Glucagon‐like peptide‐1; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2015.07.489
• Languages: English
• ISSNs: 1552-5260

Abstract

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.