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<p>Subarachnoid haemorrhage (SAH) is a life-threatening cerebrovascular event frequently accompanied by consciousness disturbances, yet the underlying mechanisms remain poorly defined. Here, we identify oligodendrocytic prosaposin (PSAP) as a critical regulator of thalamocortical connectivity and consciousness following SAH. Using multimodal approaches, including electroencephalogram and electromyogram recordings, optogenetics, single-nucleus RNA sequencing, patch-clamp recording, and magnetic resonance imaging, we demonstrate that SAH disrupts the central lateral thalamus to medial prefrontal cortex pathway via <i>Psap</i> downregulation in oligodendrocytes, leading to impaired PSAP–GPR37 interactions, myelin damage and functional connectivity loss. <i>Psap</i> overexpression or recombinant human PSAP administration restored PSAP–GPR37 interactions, preserved myelin structure and rescued central lateral thalamus to medial prefrontal cortex connectivity after SAH, resulting in improved consciousness and spatial memory. Our findings highlight oligodendrocyte dysfunction as a key mechanism underlying SAH-induced disorders of consciousness and identify PSAP as a potential therapeutic target.</p>

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Oligodendrocyte prosaposin restores subarachnoid haemorrhage-induced consciousness impairment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月2日

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  • Haiying Li,
  • Xiang Li Jr,
  • Zhongmou Xu,
  • Chang Cao,
  • Jinxin Lu,
  • Haojie Ding,
  • Lei Bai,
  • Jin Tao,
  • Lu Peng,
  • Jiping Tang,
  • Gang Chen

摘要

Subarachnoid haemorrhage (SAH) is a life-threatening cerebrovascular event frequently accompanied by consciousness disturbances, yet the underlying mechanisms remain poorly defined. Here, we identify oligodendrocytic prosaposin (PSAP) as a critical regulator of thalamocortical connectivity and consciousness following SAH. Using multimodal approaches, including electroencephalogram and electromyogram recordings, optogenetics, single-nucleus RNA sequencing, patch-clamp recording, and magnetic resonance imaging, we demonstrate that SAH disrupts the central lateral thalamus to medial prefrontal cortex pathway via Psap downregulation in oligodendrocytes, leading to impaired PSAP–GPR37 interactions, myelin damage and functional connectivity loss. Psap overexpression or recombinant human PSAP administration restored PSAP–GPR37 interactions, preserved myelin structure and rescued central lateral thalamus to medial prefrontal cortex connectivity after SAH, resulting in improved consciousness and spatial memory. Our findings highlight oligodendrocyte dysfunction as a key mechanism underlying SAH-induced disorders of consciousness and identify PSAP as a potential therapeutic target.