HMGB1 and Stroke: Evidence has shown that IL-6 secretion by astrocytes is regulated by PI3K/AKT signaling in the sub-acute phases of central nervous system injury.31 Our and other previous studies have shown that PI3K/AKT signaling is the major signaling pathway implicated in NPC proliferation and differentiation in the delayed phases of stroke recovery.32,33 In the present study, astrocytic HMGB1-induced angiogenesis in enriched mice was dependent on PI3K/AKT signaling-mediated production and secretion of IL-6 from astrocytes during stroke recovery.