SC79 exerts neuroprotective effects in the model of experimental intracerebral hemorrhage.
TL;DR
Findings indicate that SC79 attenuates inflammatory injury, oxidative damage, and neuronal apoptosis after ICH, at least in part through AKT activation, and may represent a promising therapeutic strategy for ICH.
Abstract
Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, yet specific treatments with conclusive clinical benefit remain lacking. The protein kinase B (AKT) signaling pathway is essential to various cellular functions in stroke. The present study used SC79, a specific AKT activator previously validated in ischemic stroke models, to explore therapeutic approaches for ICH in both in vivo and in vitro models. Briefly, a rat model of ICH was induced with autologous blood, and in vitro ICH models were established by Hemin stimulation of the microglial cell line RM and the neuronal cell line HT22. Neurobehavioral tests, the gravimetric (wet/dry) method, and a range of molecular techniques were used to assess neurological deficits, brain lesion, brain edema, inflammation, oxidative stress, neuronal apoptosis, and the underlying mechanisms of SC79 treatment. The results showed that SC79 promoted functional recovery after ICH, mainly reflected by suppression of neuroinflammation and oxidative stress, attenuation of neuronal apoptosis, and improvement of neurological deficits. Transcriptome sequencing and bioinformatic analyses suggested that SC79 may act through multiple pathways in addition to AKT activation. Taken together, these findings indicate that SC79 attenuates inflammatory injury, oxidative damage, and neuronal apoptosis after ICH, at least in part through AKT activation, and may represent a promising therapeutic strategy for ICH.