title: A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.
abstract: Neuroprotective actions of the peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPARγ agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Pilipović
authors.affiliation: Department of Anesthesiology, Reanimatology and Intensive Care Medicine, School of Medicine, University of Rijeka, Rijeka, Croatia; Clinics of Anesthesiology and Intensive Care Medicine, Clinical Hospital Center Rijeka, Rijeka, Croatia.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Župan
authors.affiliation: Department of Pharmacology, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Petra
authors.initials: P
authors.lastname: Dolenec
authors.affiliation: Department of Pharmacology, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Jasenka
authors.initials: J
authors.lastname: Mršić-Pelčić
authors.affiliation: Department of Pharmacology, School of Medicine, University of Rijeka, Rijeka, Croatia. Electronic address: gordana.zupan@medri.uniri.hr.
authors.forename: Gordana
authors.initials: G
authors.lastname: Župan
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009249:NADP / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D010474:Percussion / Q000009:adverse effects; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D009249:NADP; D051546:Cyclooxygenase 2; D000077205:Pioglitazone
keywords: Inflammation; Oxidative stress; Pioglitazone; Rat; Traumatic brain injury