Alterations of CaMKII after hypoxia‐ischemia during brain development

Transient brain hypoxia‐ischemia (HI) in neonates leads to delayed neuronal death and long‐term neurological deficits. However, the underlying mechanisms are incompletely understood. Calcium‐calmodulin‐dependent protein kinase II (CaMKII) is one of the most abundant protein kinases in neurons and plays crucial roles in synaptic development and plasticity. This study used a neonatal brain HI model to investigate whether and how CaMKII was altered after HI and how the changes were affected by brain development. Expression of CaMKII was markedly up‐regulated during brain development. After HI, CaMKII was totally and permanently depleted from the cytosol and concomitantly deposited into a Triton‐insoluble fraction in neurons that were undergoing delayed neuronal death. Autophosphorylation of CaMKII‐Thr286 transiently increased at 30 min of reperfusion and declined thereafter. All these changes were mild in P7 pups but more dramatic in P26 rats, consistent with the development‐dependent CaMKII expression in neurons. The results suggest that long‐term CaMKII depletion from the cytosolic fraction and deposition into the Triton‐insoluble fraction may disable synaptic development, damage synaptic plasticity, and contribute to delayed neuronal death and long‐term synaptic deficits after transient HI.