Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption.

BACKGROUND: Proteoglycan 4 (PRG4) possesses biological characteristics of anti-inflammation, lubrication, anti-apoptosis, and immunomodulation, and regulates the homeostasis of articular cartilage, myocardium, brain, and skin tissues. Nevertheless, the function of PRG4 in post-stroke hemorrhagic transformation (HT) and blood-brain barrier (BBB) disruption is unknown. METHODS: A post-stroke HT mouse model (MACO-HT) was constructed and subsequently treated with recombinant PRG4 by tail vein injection. Neurologic impairment in mice was evaluated using mNSS and Zea longa score. The effect of recombinant PRG4 on HT was assessed using HE and TTC staining and hemoglobin assays. The effect of recombinant PRG4 on BBB repair was evaluated using Evan's blue leakage, western blotting, and IF staining assays. RESULTS: Recombinant PRG4 reduced mNSS and Zea longa scores in MACO-HT mice. Infarct and hemorrhage areas and hemoglobin level in brain tissues of MACO-HT mice were significantly diminished after treatment with recombinant PRG4. MACO-HT mice exhibited significant Evan's blue leakage, which was ameliorated by reconstituted PRG4. Moreover, recombinant PRG4 notably diminished the levels of TLR2, MMP-2, and MMP-9 proteins, and augmented the levels of Claudin-5, Occludin, and ZO-1 in the brain tissues of MACO-HT mice. CONCLUSION: Recombinant PRG4 ameliorated post-stroke neurological impairment, HT, and BBB disruption. This finding identifies a biological function for PRG4 in stroke and provides support for therapeutic strategies targeting HT and BBB injury.