Neuroprotective effect of plasminogen activator inhibitor‑1 antagonist in the rat model of mild traumatic brain injury
AuthorKuru Bektaşoğlu, Pınar
Peker Eyüboğlu, İrem
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Plasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective efects. In this study, it was aimed to investigate the possible protective efects of PAI-1 antagonists in a rat mild traumatic brain injury (TBI) model. Sprague– Dawley male rats were grouped as sham (n=7), TBI (n=9), and TBI+PAI-1 antagonist (5 and 10 mg/kg TM5441 and TM5484; n=6–7). Under anesthesia, TBI was induced by dropping a metal 300-g weight from a height of 1 m on the skull. Before and 24-h after trauma neurological examination, tail suspension, Y-maze, and novel object recognition tests were performed. Twenty-four hours after TBI, the rats were decapitated and activities of myeloperoxidase, nitric oxide release, luminol-, and lucigenin-enhanced chemiluminescence were measured. Also, interleukin-1β, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-β, caspase-3, cleaved caspase-3, and PAI levels were measured with the ELISA method in the brain tissue. Brain injury was graded histopathologically following hematoxylin–eosin staining. Western blot and immunohistochemical investigation for low-density lipoprotein receptor, matrix metalloproteinase-3, and nuclear factor-κB were also performed. Data were analyzed using GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA) and expressed as means±SEM. Values of p<0.05 were considered to be statistically signifcant. Higher levels of myeloperoxidase activity in the TBI group (p<0.05) were found to be suppressed in 5 and 10 mg/kg TM5441 treatment groups (p<0.05–p<0.01). The tail suspension test score was increased in the TBI group (p<0.001) and decreased in all treatment groups (p<0.05–0.001). The histologic damage score was increased statistically signifcantly in the cortex, dentate gyrus, and CA3 regions in the TBI group (p<0.01–0.001), decreased in the treatment groups in the cortex and dentate gyrus (p<0.05–0.001). PAI antagonists, especially TM5441, have antioxidant and anti-infammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.
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