title: Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway.
abstract: Spinal cord injury (SCI) is a devastating problem of health. Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone. Exendin-4 is the longacting GLP-1 receptor agonist that used as an anti-diabetic drug. Recent studies demonstrated exendin-4 has a series of beneficial neuroprotective properties. This study was designed to assess the neuroprotective effects of exendin-4 against spinal cord injury. 72 rats were randomly divided into three groups as follows: sham operation group, SCI group, and exendin-4 group (intraperitoneal injection of exendin-4 at 10 μg/rat immediately after SCI). First, a decrease of malodialdehyde (MDA) levels and an increase of glutathione (GSH) levels in the exendin-4 group demonstrated the anti-oxidation effect of exendin-4. Further, the preservation of mitochondrial membrane potential (ΔΨm) and the reduction of cytochrome c release suggested the protection for mitochondria. Moreover, a decline of the expression level of Bax, Bcl-2 and caspase-3 and the results of TUNEL staining indicated its anti-apoptosis role. Finally, behavioral assessment with Basso Beattle Bresnahan locomotor rating scale (BBB) showed that animals in exendin-4 group achieved a significant increase in BBB scores. Our results suggest that exendin-4 prevents against SCI-induced mitochondrial apoptotic pathway and contributes to functional improvement after SCI.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Xingzhang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Jiquan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University Jinzhou 121000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D008315:Malondialdehyde; D000077270:Exenatide; D005978:Glutathione
keywords: Exendin-4; antiapoptotic; mitochondria; neuroprotective effect; spinal cord injury