Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

Holubiec, Mariana; Romero, Juan Ignacio; Suárez, Juan; Portavella, Manuel; Fernández-Espejo, Emilio; Blanco, Eduardo; Galeano, Pablo; Fonseca, Fernando Rodrı́guez de

doi:10.1007/s00213-018-4982-9

Cited by 17 publications

(19 citation statements)

References 86 publications

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“…Several preclinical and some clinical indications support the view of PEA as a therapeutic tool with high potential for the effective treatment of different pathologies characterized by neurodegeneration and neuroinflammation (Calabrò et al, 2016; Brotini et al, 2017; Holubiec et al, 2018; Impellizzeri et al, 2019). In this context, the potential beneficial effects of PEA have been demonstrated in several in vitro and in vivo experimental models of AD.…”

Section: Pea and Alzheimer’s Diseasementioning

confidence: 95%

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

2019

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N -Palmitoylethanolamide (PEA) is a non-endocannabinoid lipid mediator belonging to the class of the N -acylethanolamine phospolipids and was firstly isolated from soy lecithin, egg yolk, and peanut meal. Either preclinical or clinical studies indicate that PEA is potentially useful in a wide range of therapeutic areas, including eczema, pain, and neurodegeneration. PEA-containing products are already licensed for use in humans as a nutraceutical, a food supplement, or a food for medical purposes, depending on the country. PEA is especially used in humans for its analgesic and anti-inflammatory properties and has demonstrated high safety and tolerability. Several preclinical in vitro and in vivo studies have proven that PEA can induce its biological effects by acting on several molecular targets in both central and peripheral nervous systems. These multiple mechanisms of action clearly differentiate PEA from classic anti-inflammatory drugs and are attributed to the compound that has quite unique anti(neuro)inflammatory properties. According to this view, preclinical studies indicate that PEA, especially in micronized or ultramicronized forms (i.e., formulations that maximize PEA bioavailability and efficacy), could be a potential therapeutic agent for the effective treatment of different pathologies characterized by neurodegeneration, (neuro)inflammation, and pain. In particular, the potential neuroprotective effects of PEA have been demonstrated in several experimental models of Alzheimer’s disease. Interestingly, a single-photon emission computed tomography (SPECT) case study reported that a mild cognitive impairment (MCI) patient, treated for 9 months with ultramicronized-PEA/luteolin, presented an improvement of cognitive performances. In the present review, we summarized the current preclinical and clinical evidence of PEA as a possible therapeutic agent in Alzheimer’s disease. The possible PEA neuroprotective mechanism(s) of action is also described.

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Section: Pea and Alzheimer’s Diseasementioning

confidence: 95%

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

2019

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“…Thanks to its anti-inflammatory and analgesic properties, PEA has been investigated for the treatment of several pathologies, including stroke [134]. The molecule is active in protecting against ischemic damage in cellular and animal models of brain ischemia [135,136] and NHIBI [136]. In particular, in rats subjected to MCAO, PEA decreased the release of MCs derived chymase and tryptase [137].…”

Section: Mcs Modulation: a Promising Strategy In Stroke Treatmentmentioning

confidence: 99%

The Role of Mast Cells in Stroke

Parrella

Porrini

Benarese

et al. 2019

Cells

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Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin. Through the release of preformed mediators stored in their granules and newly synthesized molecules, they are able to initiate, modulate, and prolong the immune response upon activation. Their presence in the central nervous system (CNS) has been documented for more than a century. Over the years, MCs have been associated with various neuroinflammatory conditions of CNS, including stroke. They can exacerbate CNS damage in models of ischemic and hemorrhagic stroke by amplifying the inflammatory responses and promoting brain–blood barrier disruption, brain edema, extravasation, and hemorrhage. Here, we review the role of these peculiar cells in the pathophysiology of stroke, in both immature and adult brain. Further, we discuss the role of MCs as potential targets for the treatment of stroke and the compounds potentially active as MCs modulators.

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“…This suggests that PEA might be involved in long-term adaptation to chronic high-altitude hypoxia, likely preventing the development of chronic mountain sickness (Alarcon-Yaquetto et al, 2017). Compared with other acylethanolamides, PEA showed stronger anti-inflammatory effects reducing PA-induced astrogliosis in P30 rats' hippocampus (Holubiec et al, 2018) and preventing cortical neurons from HI-induced cell death (Portavella et al, 2018). Moreover, PEA treatment during the first hour of life in asphyctic P30 rats reduced hippocampal histological degeneration and prevented the anxiety-like behavior induced by PA (Herrera et al, 2018).…”

Section: Introductionmentioning

confidence: 93%

“…PEA (0879/10, Tocris Bioscience, Bristol, United Kingdom) was dissolved in vehicle (VHI), a solution containing 1:1:8 dimethyl sulfoxide, Tween 80, and NaCl and administered by subcutaneous injection in a volume of 10 mg/kg (Herrera et al, 2018). This dose has previously shown to be effective in animal models of experimental spinal cord injury (Genovese et al, 2008), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-inducedmodel of Parkinson's disease (Esposito et al, 2012), lipopolysaccharideinduced neuroinflammation (Sayd et al, 2014), hippocampal damage and behavioral disturbances induced by PA (Herrera et al, 2018), and cognitive function impairment and astrogliosis induced by neonatal anoxia/ischemia in rats (Holubiec et al, 2018). A preparation similar to that used in this study inhibited the response of mesolimbic dopamine neurons to nicotine in the ventral tegmental area, suggesting the ability of PEA to cross the blood-brain barrier in rats (Melis et al, 2008).…”

Section: Neuroprotection Protocolmentioning

confidence: 99%

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

et al. 2020

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Perinatal asphyxia (PA) is a clinical condition brought by a birth temporary oxygen deprivation associated with long-term damage in the corpus striatum, one of the most compromised brain areas. Palmitoylethanolamide (PEA) is a neuromodulator well known for its protective effects in brain injury models, including PA, albeit not deeply studied regarding its particular effects in the corpus striatum following PA. Using Bjelke et al. (1991) PA model, full-term pregnant rats were decapitated, and uterus horns were placed in a water bath at 37 • C for 19 min. One hour later, the pups were injected with PEA 10 mg/kg s.c., and placed with surrogate mothers. After 30 days, the animals were perfused, and coronal striatal sections were collected to analyze protein-level expression by Western blot and the reactive area by immunohistochemistry for neuron markers: phosphorylated neurofilament-heavy/medium-chain (pNF-H/M) and microtubule-associated protein-2 (MAP-2), and the astrocyte marker, glial fibrillary acidic protein (GFAP). Results indicated that PA produced neuronal damage and morphological changes. Asphyctic rats showed a decrease in pNF-H/M and MAP-2 reactive areas, GFAP + cells number, and MAP-2 as well as pNF-H/M protein expression in the striatum. Treatment with PEA largely restored the number of GFAP + cells. Most important, it ameliorated the decrease in pNF-H/M and MAP-2 reactive areas in asphyctic rats. Noticeably, PEA treatment reversed the decrease in MAP-2 protein expression and largely prevented PA-induced decrease in pNF-H/M protein expression. PA did not affect the GFAP protein level. Treatment with PEA attenuated striatal damage induced by PA, suggesting its therapeutic potential for the prevention of neurodevelopmental disorders.

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Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

Abstract: These results indicate that the acylethanolamide PEA may play an important role in the mechanisms underlying neonatal AI, and it could be a good candidate for further studies regarding neonatal AI treatments.

Cited by 17 publications

References 86 publications

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

The Role of Mast Cells in Stroke

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

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