Astrocytic mitochondria modulate poststroke splenic immune responses, promote interleukin 10 production, and mediate neuroprotection after intracerebral hemorrhage.

Background: We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)-affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses.

Methods: We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed.

Results: We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro , exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition.

Conclusions: Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.