PPARγ agonist rosiglitazone is neuroprotective after traumatic spinal cord injury via anti-inflammatory in adult rats.
Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Peroxisome proliferator-activated receptor-γ (PPARγ)  is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARγ which is shown to induce neuroprotection in animal models of focal ischemia and traumatic brain injury. SCI is induced by the application  of vascular clips (force of 24 g) to the dura via a four-level T(5)-T(8) laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of rosiglitazone, the following end points of the inflammatory process were evaluated: (1) spinal  cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) apoptosis (terminal deoxynucleotidyl transferase-mediated UTP end labeling staining and electron microscopy); (4) proinflammatory cytokines TNF-α and IL-β;  (5) PPARγ, HSP70 and HSP27 expressions. To elucidate whether the protective effects of rosiglitazone were mediated via the estrogen receptors, we investigated the effect of a PPARγ antagonist, GW9662, on the protective effects of rosiglitazone. GW9662 significantly  antagonized the effect of the rosiglitazone and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of rosiglitazone after SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.
Zhang
Qin
Q
Department of Orthopaedics, First Affiliated Hospital of Soochow University, Soochow 215006, China.
Hu
Wenzhi
W
Meng
Bin
B
Tang
Tiansi
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists* / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone