Astrocytic Prostaglandin Transporter SLCO2A1–Ca2+ Maintains Blood–Brain Barrier Integrity Against Ischemia
Taozhi Wang1,2,3 · Manping Yang2,3 · Haiyun Guo1 · Hongyu Ma2,3,4,5 · Zhenzhen Li2,3 · Junjun Kang2,3 · Yaomin Guo6 · Shengxi Wu2,3 · Yazhou Wang2,3 · Wugang Hou1,7
1 Department of Anesthesiology and Perioperative Medicine, Key Laboratory of Anesthesiology, Ministry of Education of China, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
2 Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
3 Shaanxi Province Key Laboratory of Brain Function Analysis and Modulation, Xi’an 710032, China
4 Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China
5 Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China
6 Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
7 Department of Anesthesiology, First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China
Abstract
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.
Keywords
Reactive astrocytes; Blood-brain barrier; SLCO2A1; Ca2+
