In this study, we detected that pathological stimulation of the SPAK–NKCC1 cascade after ischemic stroke causes the ChP blood–CSF barrier integrity dysfunction and elevated infiltration of T cells, CD11b+CD45+/Ly6G+ neutrophils and CD11b + CD45hi myeloid cells into both the CL and IL ChP, contributing to neuroinflammation. This evidence concerns the gene STK39 and ischemic stroke.