This study investigates the transfer of mitochondria from astrocytes to neurons after stroke, a process that may contribute to neuroprotection and neurorecovery. The authors found that astrocytes release functional mitochondria into the extracellular space, which can enter and benefit adjacent neurons. This transfer is mediated by a calcium-dependent mechanism involving CD38/cyclic ADP ribose signaling. Transient focal cerebral ischemia in mice induced the entry of astrocytic mitochondria into adjacent neurons, enhancing cell survival signals. Suppression of CD38 signaling with siRNA reduced extracellular mitochondria transfer and worsened neurological outcomes. These findings suggest a new mechanism of neuroglial crosstalk that may play a role in endogenous neuroprotective and neurorecovery mechanisms after stroke. The study also highlights the importance of CD38 in brain plasticity and the potential of targeting this pathway for therapeutic interventions.This study investigates the transfer of mitochondria from astrocytes to neurons after stroke, a process that may contribute to neuroprotection and neurorecovery. The authors found that astrocytes release functional mitochondria into the extracellular space, which can enter and benefit adjacent neurons. This transfer is mediated by a calcium-dependent mechanism involving CD38/cyclic ADP ribose signaling. Transient focal cerebral ischemia in mice induced the entry of astrocytic mitochondria into adjacent neurons, enhancing cell survival signals. Suppression of CD38 signaling with siRNA reduced extracellular mitochondria transfer and worsened neurological outcomes. These findings suggest a new mechanism of neuroglial crosstalk that may play a role in endogenous neuroprotective and neurorecovery mechanisms after stroke. The study also highlights the importance of CD38 in brain plasticity and the potential of targeting this pathway for therapeutic interventions.