Background Stroke induced alterations in the Extracellular matrix play a vital role in mediating acute pathogenesis as well as in post-stroke recovery. Tenascin-C (TNC), an adhesion-modulating extracellular matrix glycoprotein, its upregulation in adults is linked to vascular diseases. Recently, an elevated blood level of TNC in large artery atherosclerotic stroke patients and its association with post-stroke inflammation is reported. Based on the literature and our recent research investigation, we hypothesize that specific suppression of TNC immediately after ischemic stroke by using a non-viral shRNA attenuated the post-stroke acute brain damage.
Methods In order to attain our objectives, we utilized young adult male Sprague-Dawley rats. Selected animal groups were subjected to two-hour middle cerebral artery occlusion followed by three-day reperfusion with or without TNC-shRNA treatment immediately after reperfusion. We performed various techniques including TTC, Realtime-PCR, and immunoblot and immunofluorescence analysis in order to investigate the effect of our treatments and the molecular mechanisms.
Results Our results clearly demonstrated that TNC is persistently upregulated after ischemic stroke. Specific regulation of TNC immediately after ischemia inhibited the TNC levels and significantly reduced the extent of brain damage. TNC inhibition after stroke modulated the expression of excitatory amino acid transporters and tight junction proteins. Further, Early inhibition of TNC after stroke regulated the expression of key inflammatory mediators such as Toll-Like Receptor-4 and Tumor Necrosis Factor-α and Matrix metalloproteinase-9.
Conclusions Based on our results we conclude that TNC mediated several acute ischemic stroke pathogenic mechanisms. Transcriptional inactivation of TNC regulated the post-stroke alterations in excitatory amino acid transporters, tight junction proteins, and inflammatory mediators and thus attenuated the post-stroke brain damage.
Disclosures K. Johnson: None. B. Chelluboina: None.
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