Abstract | BACKGROUND: METHODS: SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α ( PPAR-αKO). To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection. RESULTS: Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. Twenty-four hours after spinal cord damage, immunohistological and biochemical studies were performed on spinal cord tissue. Our results indicate that PPAR-δ and PPAR-γ also mediated the protection induced by PEA. In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue. CONCLUSION: This study indicates that PPAR-δ and PPAR-γ can also contribute to the anti-inflammatory activity of PEA in SCI.
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Authors | Irene Paterniti, Daniela Impellizzeri, Rosalia Crupi, Rossana Morabito, Michela Campolo, Emanuela Esposito, Salvatore Cuzzocrea |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 10
Pg. 20
(Feb 01 2013)
ISSN: 1742-2094 [Electronic] England |
PMID | 23374874
(Publication Type: Journal Article)
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Chemical References |
- Amides
- Anti-Inflammatory Agents, Non-Steroidal
- Endocannabinoids
- Ethanolamines
- Neuroprotective Agents
- PPAR delta
- PPAR gamma
- Palmitic Acids
- palmidrol
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Topics |
- Amides
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(metabolism, therapeutic use)
- Endocannabinoids
(metabolism, therapeutic use)
- Ethanolamines
(metabolism, therapeutic use)
- Mice
- Mice, 129 Strain
- Mice, Knockout
- Neuroprotective Agents
(metabolism, therapeutic use)
- PPAR delta
(deficiency, genetics)
- PPAR gamma
(deficiency, genetics)
- Palmitic Acids
(metabolism, therapeutic use)
- Random Allocation
- Spinal Cord Injuries
(genetics, prevention & control)
- Time Factors
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