Lysophosphatidic Acid Reduces Ischemic Brain Injury by Attenuating Vascular Permeability Through LPA4 Receptor
Shintaro Yamada1,2, Kazuhiro Takara1,3, Naoi Hosoe1
1Department of Integrative Vascular Biology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan.
Translational Stroke Research
|June 2, 2026
Summary
Lysophosphatidic acid (LPA) treatment significantly reduced stroke-related brain damage and brain swelling by preserving blood-brain barrier integrity. This neuroprotection was mediated by the LPA4 receptor on vascular endothelial cells.
Area of Science:
- Neuroscience
- Vascular Biology
- Pharmacology
Background:
- Blood-brain barrier (BBB) disruption worsens outcomes after ischemic stroke.
- Lysophosphatidic acid (LPA) influences vascular stability, but its role in BBB protection during stroke is unknown.
Purpose of the Study:
- To investigate the neuroprotective potential of LPA in a mouse model of ischemic stroke.
- To determine the specific mechanism by which LPA affects the BBB and brain injury.
Main Methods:
- A mouse model of distal middle cerebral artery occlusion (dMCAO) was used.
- Mice received LPA treatment, and outcomes were assessed for infarct volume, edema, BBB permeability, and gene expression.
- Single-cell RNA sequencing and receptor knockout models were employed.
Main Results:
- LPA treatment reduced infarct volume by ~60% and attenuated brain edema.
- BBB integrity was preserved, with maintained claudin-5 expression in the ischemic area.
- LPA's protective effects were dependent on the LPA4 receptor, which is expressed on ischemic vascular endothelial cells.
Conclusions:
- LPA mitigates ischemic brain injury by preserving BBB integrity through an endothelial LPA4 receptor-dependent pathway.
- The LPA-LPA4 signaling axis represents a potential therapeutic target for stroke treatment.
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