Limonin attenuates neuroinflammation and enhances neurogenesis in a tMCAO mouse model of ischemic stroke

Neurogenesis in the subventricular zone (SVZ) is an effective way for brain repair after ischemic stroke. But neuroinflammation caused by cerebral ischemia would inhibit the effect of brain self-repair. As a Broadly active anti-inflammatory drugs, Limonin (LM) has a beneficial effect on ischemia-reperfusion(I/R) injury.However, the effect of LM on neurogenesis in the later stages of cerebral infarction is unknown. We speculate LM could generate anti-inflammation effect at the early stage of ischemic stroke and promote the subsequent neurogenesis. In our study, we used a transient middle cerebral artery occlusion (tMCAO) mouse model. We found LM treatment reduced the expression of iNOS and IL-1β proteins on day 3 after tMCAO. On day 7 after tMCAO, the number of BrdU/Nestin-positive cells around SVZ and BrdU/doublecortin (DCX)-positive cells in SVZ and the expression of Nestin, DCX proteins were increased through LM treatment. Moreover, on day 14 after tMCAO, the number of BrdU/DCX-positive cells in SVZ and peri-infarct area and the expression of DCX protein were increased in LM treated tMCAO mice. And LM treated tMCAO mice had fewer Cleaved-Caspase 3/DCX-positive cells in the peri-infarction zone compared to saline treated tMCAO mice 14 days after tMCAO. Finally, LM treatment increased the number of BrdU/NeuN-positive cells in the peri-infarct region and the expression of BDNF, GDNF, NGF proteins on day 14 after tMCAO. Our findings demonstrate that LM inhibits neuroinflammation and promotes neurogenesis after ischemic stroke.