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Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats

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  • Additional Information
    • Publication Information:
      De Gruyter, 2022.
    • Publication Date:
      2022
    • Collection:
      LCC:Biology (General)
    • Abstract:
      The toll-like receptor 4 (TLR4) pathway is involved in seizures. We investigated whether ultrasound-targeted microbubble destruction (UTMD)-mediated delivery of short hairpin RNA (shRNA) targeting the TLR4 gene (shRNA-TLR4) can reduce ischemia-induced seizures in rats with hyperglycemia. A total of 100 male Wistar rats were randomly assigned to five groups: (1) Sham; (2) normal saline (NS); (3) shRNA-TLR4, where rats were injected with shRNA-TLR4; (4) shRNA-TLR4 + US, where rats were injected with shRNA-TLR4 followed by ultrasound (US) irradiation; and (5) shRNA-TLR4 + microbubbles (MBs) + US, where rats were injected with shRNA-TLR4 mixed with MBs followed by US irradiation. Western blot and immunohistochemical staining were used to measure TLR4-positive cells. Half of the rats in the NS group developed tonic-clonic seizures, and TLR4 expression in the CA3 region of the hippocampus was increased in these rats. In addition, the NS group showed an increased number of TLR4-positive cells compared with the Sham group, while there was a decreased number of TLR4-positive cells in the shRNA, shRNA + US, and shRNA + MBs + US groups. Our findings indicate that the TLR4 pathway is involved in the pathogenesis of ischemia-induced seizures in hyperglycemic rats and that UTMD technology may be a promising strategy to treat brain diseases.
    • File Description:
      electronic resource
    • ISSN:
      2391-5412
    • Relation:
      https://doaj.org/toc/2391-5412
    • Accession Number:
      10.1515/biol-2022-0526
    • Accession Number:
      edsdoj.28a9a672b5f24d57a5e2c973817c7f90