protectin-d1 and Brain-Injuries--Traumatic

Traumatic brain injury (TBI) is followed by a secondary inflammation in the brain. Neuroprotectin D1 (NPD1) is synthesized from docosahexaenoic acid (DHA) and has anti-inflammatory and antiapoptotic effects in experimental models of neurodegenerative disease and brain ischemia-reperfusion. It is not known whether intralesional administration of NPD1 ameliorates inflammation and cell death after severe TBI. We therefore investigated the effects of NPD1 following a severe form of focal penetrating TBI. A total of 30 male Sprague-Dawley rats weighing between 350 and 450 g were exposed to focal penetrating TBI or sham surgery. The rats were randomized to NPD1 treatment (50 ng intralesionally, immediately following TBI) or no treatment. The rats were sacrificed at 24 or 72 h. All subgroups consisted of 5 rats. Brains were removed, fresh frozen, cut in 14-µm coronal sections and subjected to Fluoro-Jade, TUNEL, MnSOD, 3-NT, COX-2, Ox-42 and NF-κB immuno-staining and lesion size analyses. NPD1 decreased the lesion area at 72 h compared to no treatment with a mean change 42% (NPD1 14.1 mm

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Brain Injuries, Traumatic; Docosahexaenoic Acids; Head Injuries, Penetrating; Inflammation; Male; Rats; Rats, Sprague-Dawley

Currently no effective therapies are available for the treatment of traumatic brain injury (TBI). Early intervention that specifically provides neuroprotection is of most importance which profoundly influences the outcome of TBI. In the present study, we adopted a closed-skull mild TBI model to investigate potential roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in protecting against TBI. Using two-photon laser scanning microscopy (2PLSM), parenchymal cell death and reactive oxidative species (ROS) expression were directly observed and recorded after TBI through a thinned skull bone window. Fat-1 mice with high endogenous ω-3 PUFAs significantly inhibited ROS expression and attenuated parenchymal cell death after compression injury during the early injury phase. Elevated generation of glutathione (GSH) and neuroprotectin D1 (NPD1) in the parenchyma of fat-1 mice could be the contributor to the beneficial role of ω-3 PUFAs in TBI. The results of the study suggest that ω-3 PUFAs is an effective neuroprotectant as an early pharmacological intervention for TBI and the information derived from this study may help guide dietary advice for those who are susceptible to repetitive mild TBI.

Topics: Animals; Brain; Brain Injuries, Traumatic; Cadherins; Cell Death; Docosahexaenoic Acids; Fatty Acids, Omega-3; Glutathione; Mice, Inbred C57BL; Mice, Transgenic; Reactive Oxygen Species