Diabetes causes various macrovascular and microvascular alterations, often culminating in major clinical complications (first of all, stroke) that lack an eective therapeutic intervention. N-palmitoylethanolamide-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective eects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its eects in treating cerebral ischemia. Methods: Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAo) in the right hemisphere. Middle cerebral artery (MCA) occlusion was provided by introducing a 4–0 nylon monofilament (Ethilon; Johnson & Johnson, Somerville, NJ, USA) precoated with silicone via the external carotid artery into the internal carotid artery to occlude the MCA. Results: A neurological severity score and infarct volumes were carried out to assess the neuroprotective eects of PEA-OXA. Moreover, we observed PEA-OXA-mediated improvements in tissue histology shown by a reduction in lesion size and an improvement in apoptosis level (assessed by caspases, Bax, and Bcl-2 modulation and a TUNEL assay), which further supported the ecacy of PEA-OXA therapy. We also found that PEA-OXA treatment was able to reduce mast cell degranulation and reduce the MCAo-induced expression of NF-B pathways, cytokines, and neurotrophic factors. Conclusions: based on these findings, we propose that PEA-OXA could be useful in decreasing the risk of impairment or improving function in ischemia/reperfusion brain injury-related disorders.
N-Palmitoylethanolamide-Oxazoline Protects against Middle Cerebral Artery Occlusion Injury in Diabetic Rats by Regulating the SIRT1 Pathway
Fusco R.Co-primo
;Cordaro M.Co-primo
;D'Amico R.;Gugliandolo E.;Siracusa R.;Peritore A. F.;Crupi R.;Impellizzeri D.;Cuzzocrea S.
Penultimo
;Di Paola R.
Ultimo
2019-01-01
Abstract
Diabetes causes various macrovascular and microvascular alterations, often culminating in major clinical complications (first of all, stroke) that lack an eective therapeutic intervention. N-palmitoylethanolamide-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective eects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its eects in treating cerebral ischemia. Methods: Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAo) in the right hemisphere. Middle cerebral artery (MCA) occlusion was provided by introducing a 4–0 nylon monofilament (Ethilon; Johnson & Johnson, Somerville, NJ, USA) precoated with silicone via the external carotid artery into the internal carotid artery to occlude the MCA. Results: A neurological severity score and infarct volumes were carried out to assess the neuroprotective eects of PEA-OXA. Moreover, we observed PEA-OXA-mediated improvements in tissue histology shown by a reduction in lesion size and an improvement in apoptosis level (assessed by caspases, Bax, and Bcl-2 modulation and a TUNEL assay), which further supported the ecacy of PEA-OXA therapy. We also found that PEA-OXA treatment was able to reduce mast cell degranulation and reduce the MCAo-induced expression of NF-B pathways, cytokines, and neurotrophic factors. Conclusions: based on these findings, we propose that PEA-OXA could be useful in decreasing the risk of impairment or improving function in ischemia/reperfusion brain injury-related disorders.File | Dimensione | Formato | |
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Descrizione: N-Palmitoylethanolamide-Oxazoline Protects against Middle Cerebral Artery Occlusion Injury in Diabetic Rats by Regulating the SIRT1 Pathway
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