Synaptic remodeling after cortical injury: effects of neuroinflammatory modulation

Abstract

The brain is capable of plasticity, so that the structural and functional loss that are caused by cortical injury may recover. Neuroinflammatory response can greatly influence post-injury recovery by modulating synaptic plasticity. In our previous work, mesenchymal derived exosomes were found to promote functional recovery by converting microglia from a pro-inflammatory state to an anti-inflammatory state in aged rhesus monkeys after cortical injury in the primary motor cortex. In the present project, we demonstrated the effects of exosomes on synaptic changes and synapse-microglia interactions after lesion in the same monkeys. To further investigate the effects of modulating neuroinflammation on synaptic changes after injury, we also investigated dietary curcumin, an anti-inflammatory substance, in a separate group of monkeys. Both treatments showed an effect as neuroinflammatory modulators that reduced the density of microglial markers, Iba- 1/P2RY12. However, the cortical injury induced synaptic loss was reversed by the exosome treatment, whereas the other anti-inflammatory treatment, curcumin, did not show the same effect. Our results are consistent with previous study that cortical injury induced synaptic loss and microglia activation. Exosomes can both reduce inflammation and synapse loss after injury, but curcumin only showed anti-inflammatory effects. Overall, these data suggested that exosomes and curcumin had different mechanisms of how to modulate inflammation and synaptic properties to promote recovery after cortical injury.