Gene activation and protein expression following ischaemic stroke: strategies towards neuroprotection

Abstract

Current understanding of the patho-physiological events that follow acute ischaemic stroke suggests that treatment regimens could be improved by manipulation of gene transcription and protein activation, especially in the penumbra region adjacent to the infarct. An immediate reduction in excitotoxicity in response to hypoxia, as well as the subsequent inflammatory response, and beneficial control of reperfusion via collateral revascularization near the ischaemic border, together with greater control over apoptotic cell death, could improve neuronal survival and ultimately patient recovery. Highly significant differences in gene activation between animal models for stroke by middle cerebral artery occlusion, and stroke in patients, may explain why current treatment strategies based on animal models of stroke often fail. We have highlighted the complexities of cellular regulation and demonstrated a requirement for detailed studies examining cell specific protective mechanisms after stroke in humans.

Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells

“…HA was observed to play a role in the regulation of angiogenesis and vascular endothelial cell function. In particular, low-molecular-weight degradation products (3-10 disaccharide units) stimulated endothelial cell proliferation, migration, and sprouting (22). Generation of ''angiogenic'' HA from the naturally occurring HA is mediated by the endoglycosidase hyaluronidase, by processes that are associated with tissue damage, inflammatory disease, and certain types of tumors (21).…”

“…We hypothesized that hyaluronic acid (HA), a nonsulfated linear polysaccharide of (1-␤-4)D-glucuronic acid and (1-␤-3)N-acetyl-Dglucosamine, would support hESC growth in vitro, because it coregulates gene expression, signaling, proliferation, motility, adhesion, metastasis, and morphogenesis of hESCs in vivo (19). In humans, the HA content is greatest in undifferentiated cells and during early embryogenesis and then decreases at the onset of differentiation (20), where it has a crucial role in regulation of the angiogenic process (21)(22)(23). Despite its known role in embryogenesis (19,20), HA has not been used for the cultivation of hESCs.…”

Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner

“…Such interactions result in the activation of signaling cascades (13,14). Hyaluronan fragments have been shown to induce an up-regulation of early response genes (15) and a CD44-mediated activation of protein kinase C, as well as the Raf-1, MEK-1, and ERK1/2 signaling pathway in endothelial cells (16). In an attempt to investigate how hyaluronan fragments affect the differentiation of endothelial cells at the molecular level, we have studied the gene expression profile of endothelial cells in response to HA12 stimulation by using a microarray approach.…”

Angiogenic activity of latex from Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae)

“…To date, diverse studies have been conducted with the aim of finding substances that can induce angiogenesis, since the possibilities of clinical application of these substances in myocardial vascularity and the central nervous system are extensive, after injury or ischemia, partial replacement of large arteries, and even in wound healing (Krupinski et al, 2003;Slevin et al, 2005).…”