SCM-198 protects ischemic brain injury via accelerating the recovery of brain glucose metabolism, ameliorating the damage of neurons and inhibiting the activation of microglia

SCM-198 was chemically synthesized based on the structure of Leonurine and have been found to be effective in prevention of ischemic stroke; However, its therapeutic effect on ischemic stroke was poorly understood. In this study, we used rats to build up permanent middle cerebral artery occlusion (MCAO) model to determine the therapeutic effects and potential mechanism of SCM-198 on ischemic injury. 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit evaluation, F-18-FDG PET/CT scanning, transmission electron microscopy (TEM) and immunohistochemical staining were employed in the present study. TTC staining and neurological deficit evaluation results revealed that, in a 2 h window of opportunity, infarct volume and neurologic deficit scores were both decreased after SCM-198 treatment. In the PET/CT scanning study, we found the Ipsilateral-to-Contralateral ratio of all SCM-198 treatment groups were bigger than that of the MCAO group. In the TEM and immunohistochemical staining parts, we found the morphology of neurons was improved and the activation level of microglia was inhibited after SCM-198 treatment. Those results indicated that SCM-198 was a potential therapeutic option for ischemic injury in a 2 h window of opportunity, which may be related with its effects in recovering the brain glucose metabolism, ameliorating the damage of neurons and inhibiting the activation of microglia after ischemic injury happened.