N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion

Neurobiology of Disease

Maurizio Evangelista¹  Rosalia Crupi²  Ramona D'Amico²  Rosalba Siracusa²  Alessio Filippo Peritore²  Marika Cordaro²  Salvatore Cuzzocrea²  Daniela Impellizzeri²  Enrico Gugliandolo²  Stefania Petrosino³  Rosanna Di Paola⁴ 

[1] Epitech Group SpA, Via Einaudi 13, 35030, Saccolongo, Padova, Italy;Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy;Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078, Pozzuoli, Napoli, Italy;Institute of Anaesthesiology and Reanimation, Catholic University of the Sacred Heart, Rome, Italy;

关键词: Neuroprotection;    Palmitoylethanolamide;    Oxazoline;    Oxidative stress;    Inflammation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Aim: Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, animals were orally administered with 10 mg/kg of PEA-OXA daily for 15 days. Results: Brain tissues were handled for histological, immunohistochemical, western blot, and immunofluorescence analysis. PEA-OXA treatment evidently reduced the histological alterations and neuronal death induced by VaD and additionally improved behavioral deficits. Further, PEA-OXA decreased GFAP and Iba-1, markers of astrocytes, and microglia activation, as well as increased MAP-2, a marker of neuron development. Moreover, PEA-OXA reduced oxidative stress, modulated Nrf2-mediated antioxidant response, and inhibited the apoptotic process. Innovation: Some drugs may demonstrate their healing potential by regulating neuroinflammation, rather than by their habitually attributed actions only. Palmitoylethanolamide (PEA) is a prototype ALIAmide, well-known for its analgesic, anti-inflammatory, and neuroprotective properties. The inhibition of PEA degradation by targeting NAAA, its catabolic enzyme, is a different approach for treating neuroinflammation. This research offers new insight into the mechanism of PEA-OXA-induced neuroprotection. Conclusion: Thus, the modulation of intracellular NAAA by PEA-OXA could offer a novel means of controlling neuroinflammatory conditions associated with VaD.

【 授权许可】

Unknown