Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats
- Authors
- Park, Seung-Won; Yi, Jae-Hyuk; Miranpuri, Guruwattan; Satriotomo, Irawan; Bowen, Kellie; Resnick, Daniel K.; Vemuganti, Raghu
- Issue Date
- Mar-2007
- Publisher
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
- Citation
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, v.320, no.3, pp 1002 - 1012
- Pages
- 11
- Journal Title
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
- Volume
- 320
- Number
- 3
- Start Page
- 1002
- End Page
- 1012
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24130
- DOI
- 10.1124/jpet.106.113472
- ISSN
- 0022-3565
1521-0103
- Abstract
- Thiazolidinediones (TZDs) are potent synthetic agonists of the ligand-activated transcription factor peroxisome proliferator-activated receptor-gamma (PPAR gamma). TZDs were shown to induce neuroprotection after cerebral ischemia by blocking inflammation. As spinal cord injury (SCI) induces massive inflammation that precipitates secondary neuronal death, we currently analyzed the therapeutic efficacy of TZDs pioglitazone and rosiglitazone after SCI in adult rats. Both pioglitazone and rosiglitazone (1.5 mg/kg i.p.; four doses at 5 min and 12, 24, and 48 h) significantly decreased the lesion size (by 57 to 68%, p < 0.05), motor neuron loss (by 3- to 10-fold, p < 0.05), myelin loss (by 66 to 75%, p < 0.05), astrogliosis (by 46 to 61%, p < 0.05), and microglial activation (by 59 to 78%, p < 0.05) after SCI. TZDs significantly enhanced the motor function recovery (at 7 days after SCI, the motor scores were 37 to 45% higher in the TZD groups over the vehicle group; p < 0.05), but the treatment was effective only when the first injection was given by 2 h after SCI. At 28 days after SCI, chronic thermal hyperalgesia was decreased significantly (by 31 to 39%; p < 0.05) in the pioglitazone group compared with the vehicle group. At 6 h after SCI, the pioglitazone group showed significantly less induction of inflammatory genes [interleukin (IL)-6 by 83%, IL-1 beta by 87%, monocyte chemoattractant protein-1 by 75%, intracellular adhesion molecule-1 by 84%, and early growth response-1 by 67%] compared with the vehicle group (p < 0.05 in all cases). Pioglitazone also significantly enhanced the post-SCI induction of neuroprotective heat shock proteins and antioxidant enzymes. Pretreatment with a PPAR gamma antagonist, 2-chloro-5-nitro-N- phenyl-benzamide (GW9662), prevented the neuroprotection induced by pioglitazone.
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