Pegevongitide

Wistar rats (male, middle-aged, 10-12 months, multiple microinfarction-induced vascular dementia model)^[2]

1 μg/kg

i.p.; once daily; 14 days

Significantly improved white matter integrity in the corpus callosum (reduced rarefaction and vacuolation) compared to untreated multiple microinfarction rats.
Significantly attenuated demyelination in the corpus callosum and striatum compared to untreated multiple microinfarction rats.
Significantly reduced perivascular space dilation in the cortex and striatum compared to untreated multiple microinfarction rats.
Significantly increased perivascular Aquaporin-4 expression in the cortex compared to untreated multiple microinfarction rats.
Significantly improved glymphatic function: increased expression of 500 kD FITC dextran at 30 minutes and 3 hours post-infusion, increased expression of 3 kD Tetramethylrhodamine dextran at 30 minutes post-infusion, and significantly increased clearance of both tracers by 6 hours post-infusion compared to untreated multiple microinfarction rats.
Significantly decreased cerebrospinal fluid expression of inflammatory factors (tumor necrosis factor-α, chemokine ligand 9) and anti-angiogenic factors (endostatin, plasminogen activator inhibitor-1, P-selectin) compared to untreated multiple microinfarction rats.
Significantly reduced brain tissue mRNA expression of endostatin, thrombin, tumor necrosis factor-α, interleukin-6, plasminogen activator inhibitor-1, and chemokine ligand 9 compared to untreated multiple microinfarction rats.