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

David Tweedie; Lital Rachmany; Vardit Rubovitch; Yazhou Li; Harold W. Holloway; Elin Lehrmann; Yongqing Zhang; Kevin G. Becker; Evelyn Perez; Barry J. Hoffer; Chaim G. Pick; Nigel H. Greig

doi:10.1016/j.jalz.2015.07.489

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

David Tweedie^*, Lital Rachmany, Vardit Rubovitch, Yazhou Li, Harold W. Holloway, Elin Lehrmann, Yongqing Zhang, Kevin G. Becker, Evelyn Perez, Barry J. Hoffer, Chaim G. Pick, Nigel H. Greig

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	34-48
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.jalz.2015.07.489
State	Published - 1 Jan 2016

Keywords

Alzheimer's disease
Behavioral deficits
Blast injury
Exendin-4
Gene expression
Glucagon-like peptide-1
Neurodegeneration
Parkinson's disease
Traumatic brain injury

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jalz.2015.07.489

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Tweedie, D., Rachmany, L., Rubovitch, V., Li, Y., Holloway, H. W., Lehrmann, E., Zhang, Y., Becker, K. G., Perez, E., Hoffer, B. J., Pick, C. G., & Greig, N. H. (2016). Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4. Alzheimer's and Dementia, 12(1), 34-48. https://doi.org/10.1016/j.jalz.2015.07.489

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

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",

author = "David Tweedie and Lital Rachmany and Vardit Rubovitch and Yazhou Li and Holloway, {Harold W.} and Elin Lehrmann and Yongqing Zhang and Becker, {Kevin G.} and Evelyn Perez and Hoffer, {Barry J.} and Pick, {Chaim G.} and Greig, {Nigel H.}",

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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 2016, 'Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4', Alzheimer's and Dementia, vol. 12, no. 1, pp. 34-48. https://doi.org/10.1016/j.jalz.2015.07.489

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T1 - Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4

AU - Tweedie, David

AU - Rachmany, Lital

AU - Rubovitch, Vardit

AU - Li, Yazhou

AU - Holloway, Harold W.

AU - Lehrmann, Elin

AU - Zhang, Yongqing

AU - Becker, Kevin G.

AU - Perez, Evelyn

AU - Hoffer, Barry J.

AU - Pick, Chaim G.

AU - Greig, Nigel H.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Behavioral deficits

KW - Blast injury

KW - Exendin-4

KW - Gene expression

KW - Glucagon-like peptide-1

KW - Neurodegeneration

KW - Parkinson's disease

KW - Traumatic brain injury

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

Abstract

Keywords

UN SDGs

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