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Hippocampal neurodegeneration and astrocytosis following traumatic brain injury in the rat: effects of a single dose of pioglitazone

Aims: Clinically effective neuroprotective therapy for traumatic brain injury (TBI) has not yet been established although it is one of the leading causes of death and disability worldwide. The aim of this study was to examine the effects of a single dose of pioglitazone (agonist of the peroxisome proliferator-activated receptors-γ) on hippocampal neurodegeneration and astrocytosis following TBI in rats. Methods: TBI of moderate severity was performed over the left parietal cortex by the lateral fluid percussion brain injury method in adult male Wistar rats. Pioglitazone (1mg/kg) or vehicle were administered i.p. 10 min after TBI. Sham-operated, vehicle treated animals were used as the control group. Rats were sacrificed 24 h after TBI and their hippocampi were analyzed by Fluoro-Jade B (FJB) staining to identify the levels of neurodegeneration in the dentate gyrus, CA2 and CA3 regions. Western blotting analyses of the expressions of the astrocytic marker, glial fibrillary acidic protein (GFAP), in the extracts of the whole hippocampi were also performed. Results: Neurodegeneration was detected in all investigated hippocampal regions of the injured rats. Pioglitazone treatment caused significant decrease in the number of FJB positive cells in the dentate gyrus, but it had no effect on their number in the CA2 and CA3 regions. Hippocampal GFAP expression level was significantly higher following TBI and pioglitazone did not influence it. Conclusions: Our preliminary results suggest different effectiveness of pioglitazone on the neurodegeneration level in various hippocampal regions and its possible neuroprotective activity in the dentate gyrus following TBI in the rat.

hippocampus; neurodegeneration; astrocytosis; traumatic brain injury; pioglitazone; rat

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