engleski

Histological brain changes following traumatic brain injury in rats treated by pioglitazone: A preliminary study

Introduction: Processes of secondary or delayed brain damage following traumatic brain injury (TBI) are potentially reversible and could be promising targets for post-injury therapeutic interventions. Current TBI therapy is mainly supportive and non specific. In this study our focus was on pioglitazone, an agonist of the peroxisome proliferator-activated receptor (PPAR)- y. Several studies showed that PPAR-y agonists are neuroprotective in some animal models of acute and chronic CNS insults. The purpose of this study was to evaluate the histological brain changes in rats with TBI and treated by above mentioned PPAR-y agonist. Materials and Methods: Experiments were performed on adult male Wistar rats. 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 pioglitazone (I mglkg) or vehicle 10 min and 12 h after TBI. Sham-operated, vehicle-treated animals were used as the control group. Rats were sacrificed 24h after the TBI induction. The severity of the induced traumatic brain injury was validated and characterized by classical histology stainings, fluorescent DAPI nuclear staining and immunofluorescence using neuronal and glial specific cell type and cell death markers. Results: Severe tissue damage and hemorrhage was revealed in the left parietal cortex where nuclear DAPI staining showed massive pyknosis, involving primarily neuronal cells. However, immunostaining with neuronal and glial cell markers revealed loss of both neurons and glial cells at the injury site. At least some of the cell death was involving apoptotic cell death pathways and double-stranded DNA breaks. The pioglitazone treatment decreased the number of pyknotic neurons at the injury site. Conclusion: This preliminary study using immunofluorescent neuronal and glial stainings and measurements additionally suggest neuroprotective action of pioglitazone in the rat following lateral fluid percussion brain injury.

Pioglitazone; brain changes; traumatic brain injury; rat

nije evidentirano