2. Academic Validation
  3. TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway

TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway

  • J Inflamm Res. 2024 Apr 9:17:2147-2158. doi: 10.2147/JIR.S454099.
Pengwei Hou # 1,  Yang Yang # 2,  Ziqi Li # 1,  Dan Ye 2,  Li Chen 1,  Tianshun Feng 3,  Jiateng Zeng 4,  Liangfeng Wei 1,  Shousen Wang 1 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), Fuzhou, Fujian Province, People's Republic of China.
  • 2 Fuzhou General Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People's Republic of China.
  • 3 Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China.
  • 4 Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
  • 5 Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases, Fuzhou, Fujian Province, People's Republic of China.
  • # Contributed equally.
PMID: 38617382 DOI: 10.2147/JIR.S454099
Abstract

Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system Infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats.

Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3.

Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS.

Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.

Keywords

CCI; CNS infection; NF-κB activator2; TAK-3; inflammation.

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