The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury.
Traumatic spinal cord injury (SCI) is accompanied by a dramatic inflammatory response, which escalates over the first week post-injury and is thought to contribute to secondary pathology after SCI. Peroxisome proliferator-activated receptors (PPAR) are widely expressed nuclear receptors whose activation has led to diminished pro-inflammatory cascades in several CNS disorders. Therefore, we examined the efficacy of the PPARgamma agonist Pioglitazone in a rodent SCI model. Rats received a moderate mid-thoracic contusion and were randomly placed into groups receiving vehicle, low dose or high dose Pioglitazone. Drug or vehicle was injected i.p. at 15 min post-injury and then every 12 h for the first 7 days post-injury. Locomotor function was followed for 5 weeks using the BBB scale. BBB scores were greater in treated animals at 7 days post-injury and significant improvements in BBB subscores were noted, including better toe clearance, earlier stepping and more parallel paw position. Stereological measurements throughout the lesion revealed a significant increase in rostral spared white matter in both Pioglitazone treatment groups. Spinal cords from the high dose group also had significantly more gray matter sparing and motor neurons rostral and caudal to epicenter. Thus, our results reveal that clinical treatment with Pioglitazone, an FDA-approved drug used currently for diabetes, may be a feasible and promising strategy for promoting anatomical and functional repair after SCI.
McTigue
Dana M
DM
Department of Neuroscience, Center for Brain and Spinal Cord Repair and the Neuroscience Graduate Studies Program, Ohio State University, Columbus, OH 43210, USA. mctigue.2@osu.edu
Tripathi
Richa
R
Wei
Ping
P
Lash
A Todd
AT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007796:Laminectomy; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects; D009046:Motor Neurons / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000627:therapeutic use*
D039481:CD11b Antigen; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D053148:Caspase 3; D000077205:Pioglitazone