title: Intrathecal Injection of 3-Methyladenine Reduces Neuronal Damage and Promotes Functional Recovery via Autophagy Attenuation after Spinal Cord Ischemia/Reperfusion Injury in Rats.
abstract: The present study aimed to determine the occurrence of autophagy following ischemia/reperfusion (I/R) injury in the rat spinal cord and whether autophagy inhibition contributes to neural tissue damage and locomotor impairment. A spinal cord I/R model was induced via descending thoracic aorta occlusion for 10 min using systemic hypotension (40 mmHg) in adult male Sprague-Dawley rats. Then, 600 nmol 3-methyladenine (3-MA) or vehicle was intrathecally administered. Ultrastructural spinal cord changes were observed via transmission electron microscopy (TEM) and immunofluorescent double-labeling. Western blots were used to determine the protein expression of microtubule-associated protein light chain 3 (LC3) and Beclin 1. Autophagy was activated after spinal cord I/R injury as demonstrated by significantly increased LC3 and Beclin 1 expression at 3-48 h after injury. Furthermore, TEM images indicated the presence of autophagosomes and autolysosomes in the injured spinal cord. 3-MA significantly decreased LC3 and Beclin 1 expression and the number of LC3-positive cells in spinal cord of I/R versus vehicle groups. Moreover, the 3-MA-treated rats exhibited better neurobehavioral scores compared with control rats. These findings suggest activation of autophagy leading to neuronal cell death in the I/R injured spinal cord. These effects were significantly inhibited by intrathecal 3-MA administration. Thus intrathecal 3-MA administration may represent a novel treatment target following spinal cord I/R injury.
authors.affiliation: Department of Anesthesia, the Second Affiliated Hospital of Soochow University.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhou
authors.forename: Lingyun
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Fuqi
authors.initials: F
authors.lastname: Xu
authors.forename: Qirong
authors.initials: Q
authors.lastname: Dong
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000225:Adenine; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C025946:3-methyladenine