Intraventricular infusion of a low fraction of serum enhances neurogenesis and improves recovery in a rodent stroke model.

Enhancing endogenous neurogenesis is a potential therapeutic strategy in stroke treatment. We have previously demonstrated that treatment with a fraction of serum with molecular weight of less than 100 kDa (100K) combined with bFGF promoted neurogenesis of cultured stem and progenitor cells (NSPCs). In this study, we further evaluated the efficacy of intraventricular administration of 100K with bFGF (100K/bFGF) in a rat model of transient middle cerebral artery occlusion (MCAO). Rats administered 100K/bFGF on post-stroke day 1 exhibited a higher number of Ki67 and Nestin immunoreactive cells at the subventricular zone (SVZ) area and in the infarcted brain, indicating promotion of NSPCs proliferation. The 100K/bFGF treatment also predominantly increased the number of MAP-2 immunoreactive cells rather than GFAP immunoreactive cells at the SVZ area and in the infarcted regions, implying that 100K/bFGF dominated NSPCs differentiating into neurons rather than astrocytes. Importantly, treatment with 100K/bFGF significantly improved the animals' motor coordination. These findings demonstrated that treatment with a low serum fraction and bFGF benefited ischemic stroke likely through promotion of the proliferation and neuronal differentiation of endogenous NSPCs.