EPO has multiple positive effects on astrocytes in an experimental model of ischemia

Erythropoietin (EPO) has neuroprotective effects in central nervous system injury models. In clinical trials EPO has shown beneficial effects in traumatic brain injury (TBI) as well as in ischemic stroke. We have previously shown that EPO has short-term effects on astrocyte glutamatergic signaling in vitro and that administration of EPO after experimental TBI decreases early cytotoxic brain edema and preserves structural and functional properties of the blood-brain barrier. These effects have been attributed to preserved or restored astrocyte function. Here we explored the effects of EPO on astrocytes undergoing oxygen-glucose-deprivation, an in vitro model of ischemia. Measurements of glutamate uptake, intracellular pH, intrinsic NADH fluorescence, Na,K-ATPase activity, and lactate release were performed. We found that EPO within minutes caused a Na,K-ATPase-dependent increase in glutamate uptake, restored intracellular acidification caused by glutamate and increased lactate release. The effects on intracellular pH were dependent on the sodium/hydrogen exchanger NHE. In neuron-astrocyte co-cultures, EPO increased NADH production both in astrocytes and neurons, however the increase was greater in astrocytes. We suggest that EPO preserves astrocyte function under ischemic con-ditions and thus may contribute to neuroprotection in ischemic stroke and brain ischemia secondary to TBI.

Automated summary

Erythropoietin (EPO) has neuroprotective effects in models of central nervous system injury such as traumatic brain injury (TBI) and ischemic stroke. Previous studies have shown that EPO can preserve astrocyte function and decrease brain edema in TBI. In this study, the effects of EPO on astrocytes in an in vitro model of ischemia were explored, and it was found that EPO increased glutamate uptake, restored intracellular acidification, and increased lactate release, suggesting its potential contribution to neuroprotection in ischemic stroke and brain ischemia secondary to TBI.