Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury

• Published in: Inflammation 2021-12, Vol.44 (6), p.2499-2517
• Main Authors: Kuru Bektaşoğlu, Pınar, Koyuncuoğlu, Türkan, Akbulut, Selin, Akakın, Dilek, Eyüboğlu, İrem Peker, Erzik, Can, Yüksel, Meral, Kurtel, Hızır
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Antagonists; Anti-inflammatory agents; Antioxidants; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Brain Injuries, Traumatic - psychology; Caspase-3; Chemiluminescence; Cytokines; Cytokines - metabolism; Dentate gyrus; Disease Models, Animal; Enzyme-linked immunosorbent assay; IL-1β; Immunology; Inflammation; Inflammation Mediators - metabolism; Interleukin 10; Interleukin 6; Internal Medicine; Male; Matrix metalloproteinase; Maze Learning - drug effects; Metalloproteinase; Motor Activity - drug effects; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - pharmacology; Nitric oxide; Original Article; para-Aminobenzoates - pharmacology; Pathology; Pattern recognition; Peroxidase; Pharmacology/Toxicology; Piperazines - pharmacology; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Rats; Rats, Sprague-Dawley; Receptor density; Rheumatology; Statistical analysis; Traumatic brain injury
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-021-01520-0

— Plasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective effects. In this study, it was aimed to investigate the possible protective effects 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