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Pioglitazone and enoxaparin are promising novel neuroprotective drugs in the rat model of traumatic brain injury

Introduction: Traumatic brain injury (TBI) is an extremely common occurrence associated with high mortality and morbidity as well as with long-term cognitive and neurologic motor dysfunction in previously healthy population. It starts with non-reversible, and therefore, not curable, primary injury, that occurs at the moment of impact, following with delayed, potentially reversible secondary processes. All cellular and molecular substrates for post-traumatic, secondary changes have not yet been fully elucidated. Moreover, although therapeutic strategies for TBI have been the subjects of many preclinical and clinical studies, there is no available pharmaceutical treatment with proven efficacy that could reduce brain damage in this condition and significantly improve patients' clinical outcome. This study was performed with the aim to evaluate the effects of pioglitazone, an agonist of the peroxisome proliferator-activated receptor-gama (PPAR-y), and enoxaparin, low-molecular heparin, on the parameters of oxidative stress and inflammation following lateral fluid percussion brain injury in rats. Materials and Methods: TBI of moderate severity was performed over the left parietal cortex. Animals were i.p. injected with either pioglitazone or s.c. with enoxaparin in different time periods after TBI. Sham-operated, vehicle-treated animals were used as the control group. Rats were sacrificed 24 or 48 h after the TBI induction and theregions of interest were processed for spectrophotometric measurements of the oxidative lipid damage parameter's levels and the antioxidant enzymes'activities as well as for Western blotting analyses of the oxidized protein levels and inflammatory COX-2 protein expressions. Some animals were deeply anesthetized, perfused transcardially and brain slices were processed for COX-2 immunohistochemical staining. Results: TBI caused pronounced oxidative stress and inflammation in the left parietal cortex and hippocampus while the other brain regions tested in this study were not altered. Pioglitazone and enoxaparin affected some oxidative and/or inflammatory parameters following the brain trauma. Conclusions: Our findings suggest different brain structure vulnerability to oxidative stress and inflammation as well as promising neuroprotective effects of pioglitazone and enoxaparin in the rat TBI model.

Pioglitazone; enoxaparin; traumatic brain injury; rat

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