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