| Popis: |
Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with neuronal death in the hippocampus. Microglia can activate A1 astrocytes by secreting toxins. However, whether NeuroD1 application ameliorates M1microglial polarization through the reduction of A1 astrocyte remains unknown. Methods: 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100µl blood. AAV-NeuroD1-GFP virus was injected to the hippocampus 3 days post-SAH. Neurocognitive function, brain water content, In vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post virus injection. Results: NeuroD1 application dramatically attenuated SAH-induced neuroinflammation by reducing the number of reactive astrocytes and microglia, reversing the transformation of neurotoxic A1 astrocytes and decreasing the secretion of neuroinflammatory cytokines. Interestingly, NeuroD1 significantly boosted the endogenous neurogenesis at the late phase of SAH, likely benefited from the improvement of microenvironment by NeuroD1 treatment after SAH. Notably, hippocampus subgranular zone was one of the brain regions most severely affected by SAH and also the region benefited significantly from NeuroD1 treatment. Above all, NeuroD1 treatment significantly alleviated neurocognitive dysfunction by directly reduction A1astrocytes, followed by the amelioration of M1micorglia, and then restoring endogenous neurogenesis impaired by SAH. Conclusions: NeuroD1 efficiently improved neurocognitive function after SAH by modulating astrocytic and microglial polarization. Moreover, NeuroD1 boosted endogenous neurogenesis at the late phase of SAH, likely thanks to the alleviation of neuroinflammatory microenvironment. |
