Exendin-4 ameliorates traumatic brain injury-induced cognitive impairment in rats.

Abstract

Traumatic brain injury represents a major public health issue that affects 1.7 million Americans each year and is a primary contributing factor (30.5%) of all injury-related deaths in the United States. The occurrence of traumatic brain injury is likely underestimated and thus has been termed "a silent epidemic". Exendin-4 is a long-acting glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus that not only effectively induces glucose-dependent insulin secretion to regulate blood glucose levels but also reduces apoptotic cell death of pancreatic β-cells. Accumulating evidence also supports a neurotrophic and neuroprotective role of glucagon-like peptide-1 in an array of cellular and animal neurodegeneration models. In this study, we evaluated the neuroprotective effects of Exendin-4 using a glutamate toxicity model in vitro and fluid percussion injury in vivo. We found neuroprotective effects of Exendin-4 both in vitro, using markers of cell death, and in vivo, using markers of cognitive function, as assessed by Morris Water Maze. In combination with the reported benefits of ex-4 in other TBI models, these data support repositioning of Exendin-4 as a potential treatment for traumatic brain injury.

• Authors: Katharine Eakin, Yazhou Li, Yung-Hsiao Chiang, Barry J Hoffer, Hilary Rosenheim, Nigel H Greig, Jonathan P Miller
• Journal: PloS one (PLoS One) Vol. 8 Issue 12 Pg. e82016 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24312624 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• GLP1R protein, human
• Glp1r protein, rat
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Neuroprotective Agents
• Peptides
• Receptors, Glucagon
• Venoms
• Exenatide

Topics

• Animals
• Brain Injuries (drug therapy, physiopathology, prevention & control)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cognition (drug effects)
• Drug Repositioning
• Exenatide
• Glucagon-Like Peptide-1 Receptor
• Humans
• Hypoglycemic Agents
• Male
• Neurons (cytology, drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Peptides (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Glucagon (metabolism)
• Signal Transduction (drug effects)
• Venoms (pharmacology, therapeutic use)