Post-stroke recrudescence-a possible connection to autoimmunity?

Early recanalization of the occluded vessel is the only efficient intervention that improves outcome after ischemic stroke. In contrast, interventions for chronic issues facing stroke patients are limited. Recent clinical and preclinical studies have shown a correlation between upregulated immune responses to brain antigens and post-stroke recrudescence (PSR), post-stroke fatigue (PSF), and dementia (PSD); all of which are associated with poor long-term stroke outcome. Recent retrospective studies have demonstrated a strong correlation between the onset of PSR and acute infection during acute stroke, suggesting some adaptive immune system mediated pathology. This review will discuss the mechanisms and epidemiology of PSR based on the current clinical and pre-clinical evidence. Accordingly, PSR does appear correlated with populations that are prone to autoimmunity, infection, and subsequent triggers, which corroborate autoimmune responses to self-brain antigens as an underlying mechanism. Moreover, PSR as well as PSF and PSD seem to be partly explained by the development of a neuro-inflammatory response to brain antigens. Therefore, the future of improving long-term stroke outcome could be bright with more accurate pre-clinical models focusing on the role of adaptive immune-mediated post stroke neuroinflammation and more clinical studies of PSR.

Gliomagenesis is orchestrated by the Oct3/4 regulatory network.

Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by developmental hierarchical phenotypic heterogeneity, therapy resistance and recurrent growth. Neural stem cells (NSCs) from human central nervous system (CNS), and glioblastoma stem cells from patient-derived GBM (pdGSC) samples and cultured in both 2D well-plate and 3D monoclonal neurosphere culture system (pdMNCS). The pdMNCS model shows promise to establish a relevant 3D-tumor environment that maintains GBM cells in the stem cell phase within suspended neurospheres. Utilizing the pdMNCS, we examined GBM cell-lines for a wide spectrum of developmental cancer stem cell markers, including the early blastocyst inner-cell mass (ICM)-specific Nanog, Oct3/4,B, and CD133. We observed that MNCS epigenotype is recapitulated using gliomasphere-derived cells. CD133, the marker of GSC is robustly expressed in 3D-gliomaspheres and localized within the plasma membrane compartment. Conversely, gliomasphere cultures grown in conventional 2D culture quickly lost CD133 expression, indicating its variable expression is dependent on cell-culture conditions. Critically, this experiment demonstrates incomplete differentiation of cytoskeleton microtubules and intermediate filaments (IFs) of patient derived cells, similar to commercially available GBM cell lines. Subsequently, in order to determine whether Oct3/4 it was necessary for CD133 expression and cancer stemness, we transfected 2D and 3D culture with siRNA against Oct3/4 and found a significant reduction in gliomasphere formation. These results suggest that expression of Oct3/4,Aand CD133 suppress differentiation of GSCs.