Chrysophanol accelerates astrocytic mitochondria transfer to neurons and attenuates the cerebral ischemia-reperfusion injury in rats

Astrocytes release extracellular functional mitochondria and transfer them into neurons to rescue injured neurons after a stroke. However, there are no reports on drugs that might interfere with intercellular mitochondrial transfer. In this study, chrysophanol (CHR) which had proven to be an effective drug for cerebral ischemia-reperfusion injury (CIRI) was selected as the test drug to investigate whether CHR exerted a neuroprotective role by affecting the astrocytic mitochondrial transfer. We used the astrocyte-neuron co-culture system for establishing an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model in vitro and middle cerebral artery occlusion (MCAO) animal model in vivo, to investigate the effect of CHR on astrocytic mitochondrial transfer efficiency and neurons. The results showed that in the in vitro experiment, CHR improved the neuronal activity and mitochondrial function in the co-culture system by attenuating neuron injury after OGD/R. In the subsequent in vivo experiment, CHR decreased the neurological deficit score and infarction volume, recovered cell morphology, decreased the neuronal apoptosis rate in ischemic penumbra, and improved the CIRI in rats. In addition, the mitochondrial fluorescence probe labeling technique showed that CHR accelerated the transfer of mitochondria from astrocytes to neurons, suggesting that the mitochondrial transfer between astrocytes and neurons might be an important target for CHR to improve ischemic brain injury and that they might also be a potential target for ischemic brain injury drugs.