2. Academic Validation
  3. NLRP3-dependent lipid droplet formation contributes to posthemorrhagic hydrocephalus by increasing the permeability of the blood-cerebrospinal fluid barrier in the choroid plexus

NLRP3-dependent lipid droplet formation contributes to posthemorrhagic hydrocephalus by increasing the permeability of the blood-cerebrospinal fluid barrier in the choroid plexus

  • Exp Mol Med. 2023 Mar 3. doi: 10.1038/s12276-023-00955-9.
Zhaoqi Zhang 1 2 3,  Peiwen Guo 1 2 3,  Liang Liang 1 2 3,  Shiju Jila 1 2 3,  Xufang Ru 1 2 3 4,  Qiang Zhang 1 2 3,  Jingyu Chen 1 2 3,  Zhi Chen 1 2 3,  Hua Feng 5 6 7,  Yujie Chen 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
  • 2 Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
  • 3 Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
  • 4 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, China.
  • 5 Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. fenghua@tmmu.edu.cn.
  • 6 Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. fenghua@tmmu.edu.cn.
  • 7 Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. fenghua@tmmu.edu.cn.
  • 8 Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. chenyj@tmmu.edu.cn.
  • 9 Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. chenyj@tmmu.edu.cn.
  • 10 Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. chenyj@tmmu.edu.cn.
  • 11 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, China. chenyj@tmmu.edu.cn.
PMID: 36869068 DOI: 10.1038/s12276-023-00955-9
Abstract

Hydrocephalus is a severe complication that can result from intracerebral hemorrhage, especially if this hemorrhage extends into the ventricles. Our previous study indicated that the NLRP3 inflammasome mediates cerebrospinal fluid hypersecretion in the choroid plexus epithelium. However, the pathogenesis of posthemorrhagic hydrocephalus remains unclear, and therapeutic strategies for prevention and treatment are lacking. In this study, an NLRP3-/- rat model of intracerebral hemorrhage with ventricular extension and primary choroid plexus epithelial Cell Culture were used to investigate the potential effects of NLRP3-dependent lipid droplet formation and its role in the pathogenesis of posthemorrhagic hydrocephalus. The data indicated that NLRP3-mediated dysfunction of the blood-cerebrospinal fluid barrier (B-CSFB) accelerated neurological deficits and hydrocephalus, at least in part, through the formation of lipid droplets in the choroid plexus; these lipid droplets interacted with mitochondria and increased the release of mitochondrial Reactive Oxygen Species that destroyed tight junctions in the choroid plexus after intracerebral hemorrhage with ventricular extension. This study broadens the current understanding of the relationship among NLRP3, lipid droplets and the B-CSFB and provides a new therapeutic target for the treatment of posthemorrhagic hydrocephalus. Strategies to protect the B-CSFB may be effective therapeutic approaches for posthemorrhagic hydrocephalus.

Figures
Products