Abstract TP101: CaMKII Reverts After Stem Cell Treatment in Ischemic Stroke

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Background: Loss of calcium/calmodulin-dependent kinase II (CaMKII) after ischemic stroke exacerbates cell death by sensitizing vulnerable neurons to excitotoxic glutamate signaling and inducing neurotoxicity. Our recent study demonstrated the potential of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) treatment in inhibiting apoptosis after ischemic stroke. In this study, we aimed to investigate the effect of focal cerebral ischemia and/or reperfusion on CaMKII expression and the role of HUCB-MSCs treatment on CaMKII regulation. To our knowledge this is the first study that demonstrates the possible involvement of CaMKII in HUCB-MSCs-mediated neuroprotection after ischemic stroke.

Methods: Male Sprague-Dawley rats were obtained and randomly assigned to various groups. Rats were subjected to a two-hour middle cerebral artery occlusion (MCAO) procedure followed by seven days reperfusion. HUCB-MSCs (0.25x106cells/animal) were intravenously injected via tail vein 24 hours post-MCAO to designated animals. Rats brain tissues obtained seven days after reperfusion from various groups were subjected to real-time PCR, immunoblot and immunofluorescence analysis.

Results: CaMKII protein expression did not change in animals subjected to 1h, 2h, and 4h of ischemia without reperfusion. However, CaMKII expression is significantly reduced when the animals were subjected to ischemia followed by one day reperfusion. The loss of CaMKII was persistent until 14 days after reperfusion. All CaMKII isoforms (CaMKIIα, CaMKIIγ and CaMKIIδ), except CaMKIIβ, were downregulated. CaMKII expression in neurons was also reduced in the ischemic hemisphere. HUCB-MSCs treatment 24h after reperfusion revert CaMKII mRNA and protein expression. Significant co-localization of CaMKII with neurons was also noticed in rats subjected to stem cell treatment.

Conclusions: HUCB-MSCs-mediated neuroprotection after ischemic stroke could be mediated by upregulation of neuronal CaMKII expression.

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