Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4

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• 作者：David Tweedie^a ; ¹ ; ^{tweedieda@grc.nia.nih.gov" class="auth_mail" title="E-mail the corresponding author} ; Lital Rachmany^b ; ¹ ; Vardit Rubovitch^b ; Yazhou Li^a ; Harold W. Holloway^a ; Elin Lehrmann^c ; Yongqing Zhang^c ; Kevin G. Becker^c ; Evelyn Perez^d ; Barry J. Hoffer^e ; ^f ; Chaim G. Pick^b ; ^g ; ² ; Nigel H. Greig^a ; ²
• 关键词：Exendin-4 ; Blast injury ; Traumatic brain injury ; Neurodegeneration ; Alzheimer's disease ; Parkinson's disease ; Behavioral deficits ; Gene expression ; Glucagon-like peptide-1
• 刊名：Alzheimer's & Dementia
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：12
• 期：1
• 页码：34-48
• 全文大小：2626 K

文摘

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.