engleski

Potential of pioglitazone in the traumatic brain injury in the rat: effects on the hippocampal neurodegeneration and inflammation

Traumatic brain injury (TBI), frequently associated with traffic accidents, falls and sports-related injuries, results in high mortality and morbidity. Currently there is no specific therapeutic approach that would be able to limit the consequences of TBI, such as motor impairments, cognitive deficits and psychosocial disorders. Pioglitazone, a peroxisome proliferator receptor-γ agonist commonly used as glucose-lowering drug in type 2 diabetes mellitus, has been tested in different neurological disorders, e.g. cerebral ischemia, Parkinson’s and Alzheimer’s diseases. Previously, using the lateral fluid percussion injury (LFPI) model of TBI in the rat, we noted some favorable effects of this drug applied only once after the brain trauma. Purpose of this study was to assess dose-related effects of pioglitazone on the neurodegeneration and neuroinflammation in the rat hippocampus after LFPI. Animals were subjected to moderate level LFPI, induced over the left parietal cortex, midway between bregma and lambda. Ten minutes after the brain trauma rats were injected with different doses of pioglitazone with additional applications of this drug at various time points post-TBI. Seventy-two hours after the injury induction rats were killed and their brains were harvested and prepared for the histological analyses. Sham-operated animals, injected with vehicle, were used as the control group. Level of the hippocampal neurodegeneration was evaluated by the Fluoro Jade B staining. Glial activation was assessed using the immunostaining for the ionized calcium-binding adapter molecule-1, marker of the brain microglia. Preliminary results of our research showed that pioglitazone treatment exerts some limited beneficial effects on the determined histological parameters in the used experimental conditions. This work has been supported by the University of Rijeka, Croatia, under the project number 13.06.1.1.09 to G.Ž.

traumatic brain injury; hippocampus; pioglitazone; neurodegeneration; neuroinflammation

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