当前位置： SCI文献检索 > NEUROBIOLOGY OF DISEASE期刊下所有文献 > 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.

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.

Abstract：

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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Impellizzeri D,Siracusa R,Cordaro M,Crupi R,Peritore AF,Gugliandolo E,D'Amico R,Petrosino S,Evangelista M,Di Paola R,Cuzzocrea S

doi

10.1016/j.nbd.2019.01.007

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

77-91

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(18)30538-2

journal_volume

125

pub_type

杂志文章

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