Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress.

Disruption of downstream MyD88 or TRIF Toll-like receptor signaling does not protect against cerebral ischemia.

Toll-like receptor (TLR) signaling plays an important role in cerebral ischemia, but downstream signaling events, which can be organ-specific, are incompletely understood. We thereby investigated involvement of the MyD88-dependent (MyD88) and MyD88-independent (TRIF) TLR signaling pathways in 2 in vitro and 2 in vivo models of cerebral ischemia. For in vitro studies, we used a model of oxygen-glucose deprivation (OGD) followed by flow cytometric analysis to determine:1) viability of PC12 cells following knock-down with MyD88 siRNA compared to negative control siRNA and 2) viability, apoptosis and necrosis of cortical neurons from MyD88 null (-/-) , TRIF mutant, and wild type (WT) mice.

Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke.

In this study, we examined the relationship between tissue and blood levels of matrix metalloproteinase (MMP)-2 and MMP-9 through gelatin zymography at multiple time points after experimental stroke. We additionally investigated the association between these levels and the evidence of blood-cerebrospinal fluid (CSF) barrier (BCSFB) and blood-brain barrier (BBB) disruption on post-contrast fluid-attenuated inversion-recovery (FLAIR) imaging. Increased plasma MMP-9 was associated with BCSFB disruption at 1h post-reperfusion.

Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion.

At this time, the pathophysiology of macrophage involvement and their role in stroke progression are poorly understood. Recently, T2- and T2*-weighted magnetic resonance imaging (MRI), after intravenous administration of iron-oxide particles, have been used to understand the inflammatory cascade. Earlier studies report that image enhancement after stroke is from iron-laden macrophages; however, they do not account for potential blood-brain barrier disruption and nonspecific contrast enhancement.

Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats.

Neuroblasts in the subventricular zone (SVZ) proliferate markedly after brain ischemia, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, in part, because of local inflammation. In spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery occlusion, we primed E-selectin-specific regulatory T cells (Tregs) by repetitive intranasal administration of recombinant E-selectin to target local secretion of immunomodulating, antiinflammatory cytokines to activating blood vessel segments.