title: 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: Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors: Katharine
authors: K
authors: Eakin
authors: Yazhou
authors: Y
authors: Li
authors: Yung-Hsiao
authors: YH
authors: Chiang
authors: Barry J
authors: BJ
authors: Hoffer
authors: Hilary
authors: H
authors: Rosenheim
authors: Nigel H
authors: NH
authors: Greig
authors: Jonathan P
authors: JP
authors: Miller
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology* / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003071:Cognition / Q000187:drug effects*; D058492:Drug Repositioning; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide