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Effects of different doses of pioglitazone on neuronal damage, inflammation and motor performance following traumatic brain injury in the rat

Introduction: Pioglitazone, agonist of the peroxisome proliferator-activated receptor-gama, has shown to exhibit beneficial effects in various animal models of brain injury. This study was performed to determine effects of pioglitazone on the cortical damage and activation of the glial cells, as well as on motor performance following traumatic brain injury (TBI) in the rat. Methods: TBI of moderate severity was performed over the left parietal cortex using the lateral fluid percussion brain injury model. Animals were i.p. injected with either pioglitazone (1 or 3 mg/kg) or vehicle 10 minutes, 12, 24 and 48 hours after the TBI. Motor functions were evaluated at post- injury day (PID) 1, 2 and 3 using the modified neurological severity score (mNSS) and rotarod test (RRT). Rats were sacrificed 72 h after TBI and their brains were prepared for histologic analyses. Sham-operated used as the control group. Results: Brain trauma caused significant neuronal loss, apoptosis, astrocytosis and microgliosis. Pioglitazone treatment exerted significant effects on astrocytes and microglia but didn’t effect apoptotic changes and neuronal loss. All brain- injured animals exhibited statistically significant decrease in the overall motor functioning in mNSS and RRT, with pioglitazone having some limited effects on RRT performance on PID3. No significant differences between the different doses of pioglitazone were detected. Conclusions: Preliminary results of our study imply beneficial effects of pioglitazone on inflammatory reaction, limited effects on motoric performance and no effects on the neuronal loss and apoptosis in traumatized rats in used experimental conditions. This work was supported by University of Rijeka, project uniri- biomed-18- 204 to Ž.G. (from 2021 to D.P.).

traumatic brain injury, pioglitazone, neuronal damage, astrocitosis, microgliosis, motoric deficits, rat

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