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<p>Prostaglandin E2 (PGE2) plays diverse roles in secondary injury after ischemic stroke. Solute carrier organic anion transporter family member 2A1 (SLCO2A1) is a key transporter of PGE2; however, its role in the pathophysiology of cerebral ischemia remains largely unknown. Here, we report that ischemia induces transient upregulation of SLCO2A1 in reactive astrocytes. Local knockdown of <i>Slco2a1</i> in astrocytes disrupted astrocyte–endothelial cell contact, resulting in extravascular IgG accumulation and exacerbated functional deficits. In contrast, overexpression of SLCO2A1 in astrocytes significantly reduced blood–brain barrier (BBB) disruption and promoted locomotor recovery. Mechanistically, intracellular Ca<sup>2+</sup> signaling, rather than E2 prostanoid receptor signaling, was further amplified in <i>Slco2a1</i>-knockdown astrocytes and suppressed in SLCO2A1-overexpressing astrocytes following oxygen–glucose deprivation. Both pharmacological and chemogenetic manipulation of intracellular or astrocytic Ca<sup>2+</sup> effectively counteracted the effects of SLCO2A1 activity on BBB permeability and functional recovery. These data reveal a protective role of astrocytic SLCO2A1–Ca<sup>2+</sup> signaling in maintaining BBB integrity after ischemic stroke.</p>

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Astrocytic Prostaglandin Transporter SLCO2A1–Ca2+ Maintains Blood–Brain Barrier Integrity Against Ischemia

  • 期刊论文

  • 发表日期：

    2026年7月27日

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  • Taozhi Wang,
  • Manping Yang,
  • Haiyun Guo,
  • Hongyu Ma,
  • Zhenzhen Li,
  • Junjun Kang,
  • Yaomin Guo,
  • Shengxi Wu,
  • Yazhou Wang,
  • Wugang Hou

摘要

Prostaglandin E2 (PGE2) plays diverse roles in secondary injury after ischemic stroke. Solute carrier organic anion transporter family member 2A1 (SLCO2A1) is a key transporter of PGE2; however, its role in the pathophysiology of cerebral ischemia remains largely unknown. Here, we report that ischemia induces transient upregulation of SLCO2A1 in reactive astrocytes. Local knockdown of Slco2a1 in astrocytes disrupted astrocyte–endothelial cell contact, resulting in extravascular IgG accumulation and exacerbated functional deficits. In contrast, overexpression of SLCO2A1 in astrocytes significantly reduced blood–brain barrier (BBB) disruption and promoted locomotor recovery. Mechanistically, intracellular Ca2+ signaling, rather than E2 prostanoid receptor signaling, was further amplified in Slco2a1-knockdown astrocytes and suppressed in SLCO2A1-overexpressing astrocytes following oxygen–glucose deprivation. Both pharmacological and chemogenetic manipulation of intracellular or astrocytic Ca2+ effectively counteracted the effects of SLCO2A1 activity on BBB permeability and functional recovery. These data reveal a protective role of astrocytic SLCO2A1–Ca2+ signaling in maintaining BBB integrity after ischemic stroke.