sinomenine and Cerebral-Hemorrhage

Microglia polarization plays a vital role in brain inflammatory injury following intracerebral hemorrhage (ICH). Previous studies have shown that sinomenine possesses potential immunoregulatory capabilities. However, microglia polarization's exact mechanisms in ICH remain uncertain. Therefore, we examined the role of sinomenine on microglia polarization and brain inflammation following ICH. For the experiment, autologous blood models were constructed in C57/BL6 mice. Markers of classically activated (M1) and alternatively activated (M2) microglia were detected by real-time polymerase chain reaction, immunofluorescence, and flow cytometry. Microglial toxicity was assessed using MTT and FACS assays. In addition, the neurological deficit and cerebral water content of ICH mice were also observed. Sinomenine attenuated M1 markers while promoting M2 markers of microglia. Sinomenine also protected hippocampal neurons from indirect toxicity mediated by ICH-treated microglia. Additionally, administration of sinomenine inhibited matrix metalloproteinase (MMP) 3/9 expression, cerebral water content, and neurological deficit. Therefore, sinomenine protected brain function following ICH, perhaps via M2 microglia phenotype induction and MMP 3/9 inhibition. This result suggests that sinomenine is a promising therapeutical strategy in ICH.

Topics: Animals; Brain Injuries; Cell Polarity; Cell Survival; Cells, Cultured; Cerebral Hemorrhage; Encephalitis; Male; Mice; Mice, Inbred C57BL; Microglia; Morphinans

Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Microglial activation mediated cytokine and protease secretion contributes to brain injury in ICH. Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact role in ICH. In the present study, to investigate the effect of sinomenine on microglial cells inflammation, we treated ICH-challenged BV2 microglial cells with sinomenine in vitro, and explored its neuroprotection role in intracerebral hemorrhage in vivo. Changes in inflammatory cytokines, such as TNF-α, IL-1β and IL-6, reactive oxygen species (ROS) and NF-κB activation NF-κB were observed. In addition, the neurological deficit and cerebral water content of ICH mice were studied. The results demonstrated that sinomenine could inhibit the release of these cytokines and attenuate ROS production in a dose-dependent manner, and reduce NF-κB activation. Furthermore, sinomenine markedly inhibited cerebral water content and neurological deficit. In conclusion, our findings suggest that sinomenine played the protective effects through inhibition of microglial inflammation, and the findings also provided a novel therapy to treat ICH induced brain injury.

Topics: Animals; Brain Injuries; Cell Line; Cell Movement; Cerebral Hemorrhage; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Microglia; Morphinans; Neuroprotective Agents; NF-kappa B; Reactive Oxygen Species; Tumor Necrosis Factor-alpha