Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury

Guo Ying Xu, Manjit Maskey, Zizhen Wu, Qing Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Traumatic spinal cord injury (SCI) results in immediate tissue necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progressive hemorrhagic necrosis (PHN) and excessive excitation are the main sources of secondary neural injury. Recent approaches to attenuate PHN by glibenclamide can improve locomotor function after SCI. However, use of glibenclamide can exacerbate development of SCI-induced chronic pain by inhibiting KATP channels to increase neuronal excitation and glial activation. In this study, we explored a treatment strategy involving administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals following spinal cord contusion. Our goal was to determine whether this combined approach enhances both sensory and motor function. Contusive SCI was induced at spinal segment T10 in adult rats. We found that KATP channels opener, diazoxide, decreased the hyperexcitability of primary sensory neurons after SCI by electrophysiology. Timed application of glibenclamide and diazoxide following contusion significantly improved locomotor function and mitigated development of SCI-induced chronic pain, as shown by behavioral evidence. Finally, we found that timed application of glibenclamide and diazoxide attenuates the inflammatory activity in the spinal cord and increases the survival of spinal matters following SCI. These preclinical studies introduce a promising potential treatment strategy to address SCI-induced dysfunction.

Original languageEnglish (US)
Article number1440198
JournalFrontiers in Pharmacology
Volume15
DOIs
StatePublished - 2024

Keywords

  • ATP-gated potassium channels
  • chronic pain
  • diazoxide
  • glibenclamide
  • spinal cord injury

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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