N-Palmitoylethanolamide-oxazoline Treatments Protects Against Neuroinflammatory Injury Induced by Transient Middle Cerebral Artery Occlusion in Diabetic Rats

Diabetes causes various macrovascular and microvascular alterations often culminating in major clinical complications, first of all is stroke, that, until today, lacks effective therapeutic intervention. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although, recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects in treating cerebral ischemia. Neurological severity score and infarct volumes were carried out to assess the neuroprotective effects of PEA-OXA. Moreover we observed PEA-OXA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level (assessed by Caspases, Bax and Bcl-2 modulation and TUNEL assay) further support the efficacy of PEA-OXA therapy. We also found that PEA-OXA treatment was able to reduce mast cell degranulation and to block infiltration of astrocytes and microglia and reduced MCAo-induced expression of cytokines, nitrotyrosine, MDA, VEGF and TGF-, as well as was competent to re-establish growth factors such as BDNF, GDNF and NGF. PEA-OXA also inhibited the MCAo-mediated increased expression of NAAA and NF-κB and degradation of IκB-α. PEA-OXA treated injured animals also improved neurobehavioral functions as evaluated by water maze test. Based on these findings, we propose that PEA-OXA would be useful in decreasing the risk of impairment or improving function in ischemia-reperfusion brain injury-related disorders.