No abstract

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt–β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood–brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt–β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.

Gamboge is the dry resin secreted by Garcinia hanburyi Hook.f, with the function of promoting blood circulation, detoxification, hemostasis and killing insects, used for the treatment of cancer, brain edema and other diseases. Gambogic acid is the main effective constituent of Gamboge. The present study investigated the protective effects of gambogic acid on spinal cord injury (SCI) and its anti‑inflammatory mechanism in an SCI model in vivo. Basso, Beattie and Bresnahan (BBB) testing was used to detect the protective effects of gambogic acid on nerve function of SCI rats. The water content of the spinal cord was used to analyze the protective effects of gambogic acid on the damage of SCI. Treatment with gambogic acid effectively improved BBB scores and inhibited water content of the spinal cord in SCI rats. Also, gambogic acid significantly reduced inflammatory cytokines levels of [tumor necrosis factor‑α, interleukin (IL)‑6, IL‑12 and IL‑1β] and oxidative stress (malondialdehyde, superoxide dismutase, glutathione and glutathione‑peroxidase) factors, and suppressed receptor activator of nuclear factor κB ligand, phosphorylated p38 protein expression and toll‑like receptor 4/nuclear factor‑κB pathway activation, and increased phosphatidylinositol 3‑kinase/protein kinase B (Akt) pathway activation in SCI rats. These results provide evidence that gambogic acid inhibits SCI and inflammation through suppressing the p38 and Akt signaling pathways.