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Updated: Oct 14, 2025

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Knockdown of rno_circRNA_009194 Improves Outcomes in Traumatic Brain Injury Rats through Inhibiting Voltage-Gated

Xian-Jian Huang1, Gao-Jian Su1, Chu-Wei Wu1

  • 1Shenzhen Key Laboratory of Neurosurgery, Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Journal of Neurotrauma
|November 2, 2021
PubMed
Summary

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This study reveals that reducing circRNA_009194 levels improves neurological outcomes after traumatic brain injury (TBI) in rats. Knockdown of circRNA_009194 inhibits Nav1.3, offering a potential therapeutic target for TBI.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Excessive activation of voltage-gated sodium channel Nav1.3 is implicated in secondary traumatic brain injury (TBI).
  • The precise molecular mechanisms regulating Nav1.3 in TBI remain incompletely understood.

Purpose of the Study:

  • To investigate the role of circular RNAs (circRNAs) in regulating Nav1.3 expression and neurological outcomes following TBI.
  • To elucidate the molecular mechanisms involving circRNAs, microRNAs, and transcription factors in TBI.

Main Methods:

  • A TBI rat model was established using a fluid percussion device.
  • circRNA microarray analysis identified differentially expressed circRNAs in the hippocampus post-TBI.
  • Functional experiments involved lentiviral-mediated manipulation of circRNA_009194, miR-145-3p, Sp1, and Nav1.3.
Keywords:
Nav1.3Sp1circRNA microarraycircRNA_009194miR-145-3ptraumatic brain injury

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  • Neurological outcomes were assessed using behavioral tests (Morris water maze, mNSS), brain water content, and histological staining.
  • Molecular mechanisms were explored via PCR, Western blotting, luciferase reporter assays, ChIP, and EMSA.

    • Main Results:

    • A total of 347 circRNAs were differentially expressed post-TBI, with 234 upregulated and 113 downregulated.
    • circRNA_009194 showed significant upregulation (FC=4.45) and was selected for further study.
    • Downregulation of circRNA_009194 improved neurological scores (27.5% reduced mNSS) and modulated miR-145-3p, Sp1, and Nav1.3 levels.
    • These effects were reversed by inhibiting miR-145-3p or overexpressing Sp1/Nav1.3.
    • circRNA_009194 functions as a sponge for miR-145-3p, regulating Sp1-mediated Nav1.3 expression.

    Conclusions:

    • circRNA_009194 plays a critical role in TBI pathogenesis by modulating Nav1.3 expression.
    • Knockdown of circRNA_009194 ameliorates neurological deficits in a TBI rat model.
    • The findings suggest circRNA_009194 as a potential therapeutic target for improving outcomes in TBI.