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

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dc.contributor.authorERZİK, CAN
dc.contributor.authorsKuru Bektasoglu, Pinar; Koyuncuoglu, Turkan; Akbulut, Selin; Akakin, Dilek; Eyuboglu, Irem Peker; Erzik, Can; Yuksel, Meral; Kurtel, Hizir
dc.date.accessioned2022-03-12T22:57:57Z
dc.date.available2022-03-12T22:57:57Z
dc.date.issued2021
dc.description.abstractPlasminogen 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-1 beta, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-beta, 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-kappa B 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 significant. 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 significantly 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-inflammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.
dc.identifier.doi10.1007/s10753-021-01520-0
dc.identifier.eissn1573-2576
dc.identifier.issn0360-3997
dc.identifier.pubmed34460025
dc.identifier.urihttps://hdl.handle.net/11424/237121
dc.identifier.wosWOS:000691757800003
dc.language.isoeng
dc.publisherSPRINGER/PLENUM PUBLISHERS
dc.relation.ispartofINFLAMMATION
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectantioxidant
dc.subjectanti-inflammatory
dc.subjectneuroprotection
dc.subjectPlasminogen activator inhibitor-1 antagonist
dc.subjecttraumatic brain injury
dc.subjectNF-KAPPA-B
dc.subjectROLES
dc.subjectTHROMBOGENESIS
dc.subjectCONSEQUENCES
dc.subjectPROTEINASE
dc.subjectEXPRESSION
dc.subjectPROTEASE
dc.subjectCLEAVAGE
dc.subjectRELEASE
dc.subjectSTROKE
dc.titleNeuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury
dc.typearticle
dspace.entity.typePublication
local.avesis.id9568967b-c12f-4259-829a-819e9cf59763
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages19
oaire.citation.endPage2517
oaire.citation.issue6
oaire.citation.startPage2499
oaire.citation.titleINFLAMMATION
oaire.citation.volume44
relation.isAuthorOfPublication5081a883-9590-4d5d-8e2a-f83c8916241d
relation.isAuthorOfPublication.latestForDiscovery5081a883-9590-4d5d-8e2a-f83c8916241d

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