Toll-Like Receptor 4 Signaling in Focal Cerebral Ischemia: a Focus on the Neurovascular Unit.

A robust innate immune activation leads to downstream expression of inflammatory mediators that amplify tissue damage and consequently increase the morbidity after stroke. The Toll-like receptor 4 (TLR4) pathway is a major innate immune pathway activated acutely and chronically after stroke. Hence, understanding the intricacies of the temporal profile, specific control points, and cellular specificity of TLR4 activation is crucial for the development of any novel therapeutics targeting the endogenous innate immune response after focal cerebral ischemia. The goal of this review is to summarize the current findings related to TLR4 signaling after stroke with a specific focus on the components of the neurovascular unit such as astrocytes, neurons, endothelial cells, and pericytes. In addition, this review will examine the effects of focal cerebral ischemia on interaction of these neurovascular unit components.

Carotid atherosclerotic plaques from symptomatic stroke patients share the molecular fingerprints to develop in a neoplastic fashion: a microarray analysis study.

Identification of genetic mechanisms that promote the onset of stroke and transient cerebral ischemic attack symptoms in carotid atherosclerotic patients would further our understanding of the pathophysiology of this disease and could lead to new pharmacological and molecular therapies. Using Affymetrix Human Genome 230 GeneChip set, the present study evaluated the gene expression differences in geometrically similar carotid artery plaque samples extricated from six symptomatic stroke patients and four asymptomatic patients. There was no significant difference in the degree of stenosis between the two groups. Of the 44,860 transcripts analyzed, 289 (approximately 0.6% of the total transcripts) were differentially expressed between the plaques from the symptomatic and asymptomatic groups (236 were expressed more abundantly and 53 were expressed less abundantly in the symptomatic group). Of the 236 transcripts expressed more abundantly in the symptomatic plaques, 71% (167 transcripts) indicate an active cell proliferation and neoplastic process. These include oncogenes, growth factors, tumor promoters, tumor markers, angiogenesis promoters, transcription factors, RNA splicing factors, RNA processing proteins, signal transduction mediators and those that control the metabolism. Real-time polymerase chain reaction confirmed the increased expression of 63 transcripts in the symptomatic plaques. The other groups of transcripts expressed more abundantly in the symptomatic plaques are those that control ionic homeostasis, those that participate in the progression of degenerative neurological diseases (Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's disease) and epilepsy. This indicates that symptomatic plaques are molecularly and biochemically more active than the asymptomatic plaques, or active plaque growth precipitates stroke symptoms.