Author + information
- Yonggang Yao and
- Chunyu Zeng
Ischemic injury to neurons represents the underlying cause of stroke to the brain. Our previous studies identified MG53 as an essential component of the cell membrane repair machinery. Here we show that the recombinant human (rh)MG53 protein facilitates repair of ischemia-reperfusion (IR) injury to the brain.
We will establish cerebral ischemia reperfusion model in SD rats using the method of MCAO, randomly divided into sham operation group,Ischemia reperfusion group and Ischemia reperfusion +rhMG53 group.Then,observing the Zea-Longa score of nervous system and Brain tissue TTC staining and pathological sections. We will reveal the mechanism how rhMG53 protect the brain from ischemia reperfusion injury with Western Blot and the apoptosis of brain tissue with TUNEL staining. We detective the process of rhMG53 crossing blood-brain barrier using Small Animal In Vivo Imaging system.
MG53 rapidly moves to acute injury sites on neuronal cells to form a membrane repair patch. IR-induced brain injury increases permeability of the blood-brain-barrier, providing access of MG53 from blood circulation to target the injured brain tissues. Exogenous rhMG53 protein can protect cultured neurons against hypoxia/reoxygenation-induced damages. Transgenic mice with increased levels of MG53 in the bloodstream are resistant to IR-induced brain injury. Intravenous administration of rhMG53, either prior to or after ischemia, can effectively alleviate brain injuries in rats. The rhMG53-mediated neuroprotection involves suppression of apoptotic neuronal cell death, as well as activation of the pro-survival RISK signaling pathway.
Our data indicate a physiological function for MG53 in the brain and suggest that targeting membrane repair or RISK signaling may be effective means for treatment of ischemic brain injuries.
K signaling pathway.