ScholarWorksIndianapolis
  • Communities & Collections
  • Browse ScholarWorks
  • English
  • Català
  • Čeština
  • Deutsch
  • Español
  • Français
  • Gàidhlig
  • Italiano
  • Latviešu
  • Magyar
  • Nederlands
  • Polski
  • Português
  • Português do Brasil
  • Suomi
  • Svenska
  • Türkçe
  • Tiếng Việt
  • Қазақ
  • বাংলা
  • हिंदी
  • Ελληνικά
  • Yкраї́нська
  • Log In
    or
    New user? Click here to register.Have you forgotten your password?
  1. Home
  2. Browse by Subject

Browsing by Subject "Undercut"

Now showing 1 - 1 of 1
Results Per Page
Sort Options
  • Loading...
    Thumbnail Image
    Item
    Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice
    (Wiley, 2021) Ping, Xingjie; Chai, Zhi; Wang, Weiping; Ma, Cungen; White, Fletcher A.; Jin, Xiaoming; Anatomy, Cell Biology and Physiology, School of Medicine
    Objective: Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis. Methods: In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology. Results: Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAb- or TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation. Significance: RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.
About IU Indianapolis ScholarWorks
  • Accessibility
  • Privacy Notice
  • Copyright © 2025 The Trustees of Indiana University