title: Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.
abstract: Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI.
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Jee Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Hae Y
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: tyune@khu.ac.kr.
authors.forename: Tae Y
authors.initials: TY
authors.lastname: Yune
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Blood spinal cord barrier; Fluoxetine; Inflammation; Matrix metalloprotease-9; Vitamin C