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 Jan;12(1):34-48. doi: 10.1016/j.jalz.2015.07.489. Epub 2015 Aug 29.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blast Injuries / drug therapy*
  • Blast Injuries / pathology
  • Brain Concussion / drug therapy*
  • Brain Concussion / metabolism
  • Brain Concussion / pathology
  • Cognition / drug effects
  • Cognition Disorders / prevention & control*
  • Exenatide
  • Gene Expression / drug effects
  • Glucagon-Like Peptide 1 / agonists*
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neuroprotective Agents / administration & dosage
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Venoms / pharmacology
  • Venoms / therapeutic use*

Substances

  • Neuroprotective Agents
  • Peptides
  • Venoms
  • Glucagon-Like Peptide 1
  • Exenatide