Scholarlink

<p>Postoperative sleep deprivation (PSD) exacerbates perioperative neurocognitive disorders (PND) through unresolved neuroinflammation, yet the underlying mechanisms remain elusive. Here, we aim to evaluate contribution of disregulation of the meningeal lymphatic vessels (MLVs) to PSD-induced cognitive decline. In a mosue model combining tibial fracture surgery with sleep deprivation, PSD induced spatial and contextual memory deficits, concurrent with hippocampal neuroinflammation and microglial activation. Crucially, PSD induced significant MLVs structural regression and functional impairment, which further limited drainage of inflammatory mediators (IL-1β, IL-6, and TNF-α) to deep cervical lymph nodes. Lymphatic ligation that suppressed cytokine trafficking to peripheral lymphatics amplifies hippocampal inflammation. Overexpression of vascular endothelial growth factor C (VEGF-C) by intracisternal delivery of AAV-VEGF-C to enhance MLVs function restored lymphatic drainage capacity, attenuated hippocampal neuroinflammation, and rescued PSD-induced cognitive decline. Our findings exhibit a MLVs-related pathological mechanism in PSD-related cognition impairment, showing that sleep loss disrupts meningeal lymphatic integrity, which further impairs inflammatory clearance and exaggrates neuroinflammation and neuronal dysfunction. Therapeutic targeting of restore MLVs’ function may thus offer a novel strategy to mitigate PND.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Meningeal lymphatic dysfunction mediates postoperative sleep deprivation-induced cognitive decline via impaired neuroinflammatory clearance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Binkang Huang,
  • Wei Tu,
  • Han Zhou,
  • Lan Mo,
  • Qiubo Yang,
  • Yilong Sheng,
  • Daofan Sun,
  • Bo Meng,
  • Zhexi Chi,
  • Yingying Lv,
  • Rongjun Liu,
  • Xiuzhong Xing,
  • Hui Yuan,
  • Jing Yang,
  • Fengdeng Hu,
  • Guo Chen,
  • Junping Chen,
  • Xiaowei Chen,
  • Bo Lu

摘要

Postoperative sleep deprivation (PSD) exacerbates perioperative neurocognitive disorders (PND) through unresolved neuroinflammation, yet the underlying mechanisms remain elusive. Here, we aim to evaluate contribution of disregulation of the meningeal lymphatic vessels (MLVs) to PSD-induced cognitive decline. In a mosue model combining tibial fracture surgery with sleep deprivation, PSD induced spatial and contextual memory deficits, concurrent with hippocampal neuroinflammation and microglial activation. Crucially, PSD induced significant MLVs structural regression and functional impairment, which further limited drainage of inflammatory mediators (IL-1β, IL-6, and TNF-α) to deep cervical lymph nodes. Lymphatic ligation that suppressed cytokine trafficking to peripheral lymphatics amplifies hippocampal inflammation. Overexpression of vascular endothelial growth factor C (VEGF-C) by intracisternal delivery of AAV-VEGF-C to enhance MLVs function restored lymphatic drainage capacity, attenuated hippocampal neuroinflammation, and rescued PSD-induced cognitive decline. Our findings exhibit a MLVs-related pathological mechanism in PSD-related cognition impairment, showing that sleep loss disrupts meningeal lymphatic integrity, which further impairs inflammatory clearance and exaggrates neuroinflammation and neuronal dysfunction. Therapeutic targeting of restore MLVs’ function may thus offer a novel strategy to mitigate PND.