H2S prevents peripheral immune cell invasion, increasing [Ca2+]i and excessive phagocytosis following hypoxia-ischemia injury in neonatal mice

We previously reported that L-Cysteine, H2S donor, remarkably attenuated neuminflammation following hypoxia-ischemia (HI) brain injury in neonatal mice. However, its anti-inflammatory mechanism for HI insult is still unknown. The study focus on the effects of L-Cysteine on immune cell populations, Ca2+ mobilization and phagocytosis after neonatal HI. We found that L-Cysteine treatment skewed CD11b(+)/CD45(high) micmglia and CD11b(+)/CD45(high) brain monocytes/macrophages towards a more anti-inflammatory property 72 h after HI-injured brain. Moreover, L-Cysteine treatment reduced cerebral infiltration of CD4 T cells 7 days following HI insult. Furthermore, CD4 T cell subset analysis revealed that L-Cysteine treatment decreased Th1 and Th2 counts, while increased Th17/Th2 ratio. Moreover, L-Cysteine treatment suppressed LPS-induced cytosolic Ca2+ and LPS-stimulated phagocytosis in primary microglia. The anti-inflammatory effect of L-Cysteine was associated with improving neurobehavioral impairment following HI insult. Our results demonstrate L-Cysteine treatment suppressed the invasion of peripheral immune cells, increasing [Ca2+]i and excessive phagocytosis to improve neurobehavioral deficits following hypoxia-ischemia injury in neonatal mice by H2S release.

Automated summary

The study found that L-Cysteine treatment after neonatal hypoxia-ischemia brain injury can modulate immune cell populations, inhibit peripheral immune cell invasion, reduce Ca2+ mobilization, and improve neurobehavioral deficits.