Mild hypothermia facilitates mitochondrial transfer from astrocytes to injured neurons during oxygen-glucose deprivation/reoxygenation

摘要

Mitochondrial dysfunction is now considered an important sign of neuronal death during cerebral ischemia/ reperfusion (I/R) injury. Studies have shown that the transfer of mitochondria from astrocytes to injured neurons contributes to endogenous neuroprotection after stroke. Basic and clinical studies have shown that mild hypothermia exerts a clear protective effect on neurons after cerebral ischemic injury, but the role of mild hypothermia in this endogenous neuroprotective mechanism remains unclear. Here, we established a neuronal cell oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R)-induced injury model and explored the effect of mild hypothermia on the transfer of mitochondria from astrocytes to injured neurons. Astrocytes in the hypothermia group (33 degrees C) released more functional mitochondria into the extracellular medium than those in the normal temperature group (37 degrees C). Compared with cells in the normal temperature group, OGD-injured neuronal cells in the mild hypothermia group exhibited an increased intracellular ATP content, mitochondrial membrane potential (MMP) and cellular viability and a decreased death rate after the addition of astrocyte-derived conditioned medium. Based on the results of this study, mild hypothermia promotes endogenous neuroprotective effects through a mechanism related to functional mitochondria released from astrocytes into the extracellular space and transferred into injured neurons.