Neuroprotective effects of Co-ultraPEALut on secondary inflammatory process and autophagy involved in traumatic brain injury.

Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. In the present study, we performed a widely-used model of TBI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound Co-ultraPEALut. We demonstrated that the treatment with Co-ultraPEALut resulted in a significant improvement of motor and cognitive recovery after controlled cortical impact (CCI), as well as markedly reducing lesion volumes. Moreover, our results revealed the ability of Co-ultraPEALut, to reduce brain trauma through modulation of NF-κB activation. In addition, treatment with Co-ultraPEALut significantly enhanced the post-TBI expression of the neuroprotective neurotrophins GDNF compared to vehicle. Co-ultraPEALut at the dose of 1 mg/kg, also modulated apoptosis, the release of cytokine and ROS, the activation of chymase, tryptase and nitrotyrosine and inhibited autophagy. Thus, our data demonstrated that Co-ultraPEALut at a lower dose compared to PEA alone, can exert neuroprotective effects and the combination of both could improve their ability to counteract the neurodegeneration and neuroinflammation induced by TBI.