Rat brain phospholipid remodeling correlates with plasma lipid clearance and late functional vulnerability after ischemic stroke.

Post-stroke neurological decline is associated with persistent vascular and metabolic dysfunction, including long-term alterations in lipid homeostasis. We performed targeted lipidomic analyses in the hippocampus and plasma from rats subjected to transient middle cerebral artery occlusion at 6 h, 24 h, 7 days, 15 days, 1 month, and 4 months after stroke. Lipid profiles were integrated with behavioral, histological, immunofluorescence, western blot, flow cytometric, and bioinformatic analyses. At 4 months, an increased plasma lysophosphatidylcholine/phosphatidylcholine ratio was associated with late neurological deterioration and cognitive impairment. This change coincided with hippocampal lipid remodeling, region-specific astrogliosis, changes in PLA2, LPCAT1, MBOAT1, and SREBF2, and altered circulating BODIPY+ lipophilic particles associated with apolipoproteins. These findings support coordinated central and peripheral lipid remodeling during chronic post-ischemic progression with potential relevance for peripheral biomarker development.