Ceruloplasmin Plays a Neuroprotective Role in Cerebral Ischemia, Front Neurosci. 2019

“...Concluding Remarks
This study further elucidates the role of Cp in ischemic stroke. Ceruloplasmin has two fundamental roles (i) in oxidizing ferrous iron and (ii) in the egress of ferrous iron out of cells via Fpn. Lack of Cp, therefore, leads to excess iron buildup in cells. Using wildtype and Cp null mice, we provide clear evidence that Cp has tissue protective effects in the acute phase (24 h) as the ischemic lesion size is larger in Cp null mice. Further evidence of the importance of this antioxidant in the acute phase after pMCAO is suggested by the ninefold increase in its expression at 72 h. In addition, our functional analysis revealed that the absence of Cp leads to worsening of functional recovery at 7 and 14 days after onset of ischemia. This suggests a late effect which could be due to detrimental effects on synaptic reorganization and circuitry via free-radical mediated effects on neurons, astrocytes and microglia. Future work will need to address if Cp influences microglial and astrocyte responses after ischemic stroke that can impact on functional recovery. Analysis of dendritic arborizations and dendritic spines in the penumbral regions of the cortex in wildtype and Cp null mice will also be worth assessing. Evidence of increased iron in the ischemic tissue was detected by iron histochemistry. Furthermore, immunofluorescence staining for ferritin (a surrogate marker for iron) showed increased ferritin in both astrocytes and macrophages/microglia after pMCAO in wildtype mice but this is significantly higher in astrocytes in Cp null mice. These perturbations in iron levels in the tissue was accompanied by increased oxidative damage to lipids and proteins. There is evidence that systemic treatment with Cp improves outcome after ischemic stroke in rodents. Our current study shows that the increased expression of Cp in the ischemic cortex of wildtype mice has important neuroprotective effects after cerebral ischemia...”
Full paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331473/