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


CONCLUSIONS
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.
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Electronic address: tweedieda@grc.nia.nih.gov.
David
D
Tweedie
Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Lital
L
Rachmany
Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Vardit
V
Rubovitch
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Yazhou
Y
Li
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Harold W
HW
Holloway
Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Elin
E
Lehrmann
Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Yongqing
Y
Zhang
Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Kevin G
KG
Becker
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Evelyn
E
Perez
Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Graduate Program in Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
Barry J
BJ
Hoffer
Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
Chaim G
CG
Pick
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Nigel H
NH
Greig
D000818:Animals; D001753:Blast Injuries / Q000188:drug therapy* / Q000473:pathology; D001924:Brain Concussion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000517:prevention & control*; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
Alzheimer's disease; Behavioral deficits; Blast injury; Exendin-4; Gene expression; Glucagon-like peptide-1; Neurodegeneration; Parkinson's disease; Traumatic brain injury