A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury

Journal of Neuroinflammation

Emanuela Esposito²  Salvatore Cuzzocrea²  Michele Navarra¹  Rosanna Di Paola²  Daniela Impellizzeri²  Irene Paterniti² 

[1] Pharmaco-Biological Department, University of Messina, Viale Annunziata, 98100 Messina, Italy;Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, Italy

关键词: Spinal cord injury;    Neuroinflammation;    Antioxidant action;    Luteolin;    Palmitoylethanolamide;   

Others  :  1152479
DOI  :  10.1186/1742-2094-10-91

 received in 2013-05-23, accepted in 2013-07-09,  发布年份 2013

【 摘 要 】

Background

It has recently been demonstrated that palmitoylethanolamide (PEA), an endogenous lipid amide belonging to the N-acylethanolamine family, exerts neuroprotection in central nervous system (CNS) pathologies. In recent studies, we have demonstrated that treatment with PEA significantly reduced inflammatory secondary events associated with spinal cord injury (SCI). Since oxidative stress is considered to play an important role in neuroinflammatory disorders, in the present work we studied a new composite, a formulation including PEA and the antioxidant compound luteolin (Lut), subjected to an ultramicronization process, co-ultraPEALut. We investigated the effect of co-ultraPEALut (in the respective fixed doses of 10:1 in mass) in both an ex vivo organotypic spinal cord culture model and an in vivo model of SCI.

Methods

For the organotypic cultures, spinal cords were prepared from mice at postnatal day 6 and were cut into transverse slices of 400 μm thickness to generate the lumbar organotypic slice cultures. After 7 days of culturing, the slices were mechanically injured onto the center of the slice and the co-ultraPEALut was applied at different concentrations (0.00009, 0.0009 and 0.009 g/l) 1 hour before damage. For in vivo studies, SCI was induced in mice through 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 co-ultraPEALut (1 mg/kg ip) was administered at 1 and 6 hours after SCI. At 24 hours after SCI, mice were sacrificed and the spinal cords were collected for further evaluation. Additional animals were treated similarly and sacrificed 10 days after SCI.

Results

Pretreatment with co-ultraPEALut significantly reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner, restored neuronal nitric oxide synthase (nNOS) expression at all three tested concentrations, and protected cells by cell death (MTT assay) in spinal cord organotypic cultures. Moreover, we demonstrated in vivo that co-ultraPEALut 1 mg/kg reduced the severity of trauma induced by compression and improved the motor activity evaluated at 10 days post-injury.

Conclusion

The present study demonstrates that the protective effect of PEA on SCI-associated neuroinflammation could be improved by co-ultramicronization with Lut possibly due to its antioxidant properties.

【 授权许可】

   
2013 Paterniti et al.; licensee BioMed Central Ltd.

【 图 表 】

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