Probing Interleukin-6 in Stroke Pathology and Neural Stem Cell Transplantation.

Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3-4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction size, improve neurobehavioral performance, and reduce inflammatory agents including interleukins. Typically, interleukin-6 (IL-6) is regarded as proinflammatory, and thus, preclinical studies often discuss it as beneficial for neurological recuperation when stem cells reduce IL-6's expression. However, some studies have also demonstrated neurological benefit with upregulation of IL-6 or preconditioning of stem cells with IL-6. This review specifically focuses on stem cells and IL-6, and their occasionally disparate, occasionally synergistic roles in the setting of ischemic cerebrovascular insults.

Minor Changes for a Major Impact: A Review of Epigenetic Modifications in Cell-Based Therapies for Stroke.

Epigenetic changes in stroke may revolutionize cell-based therapies aimed at reducing ischemic stroke risk and damage. Epigenetic changes are a novel therapeutic target due to their specificity and potential for reversal. Possible targets for epigenetic modification include DNA methylation and demethylation, post-translational histone modification, and the actions of non-coding RNAs such as microRNAs. Many of these epigenetic modifications have been reported to modulate atherosclerosis development and progression, ultimately contributing to stroke pathogenesis. Furthermore, epigenetics may play a major role in inflammatory responses following stroke. Stem cells for stroke have demonstrated safety in clinical trials for stroke and show therapeutic benefit in pre-clinical studies. The efficacy of these cell-based interventions may be amplified with adjunctive epigenetic modifications. This review advances the role of epigenetics in atherosclerosis and inflammation in the context of stroke, followed by a discussion on current stem cell studies modulating epigenetics to ameliorate stroke damage.