Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

Abstract

Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS) demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release and the production of several other angiogenic molecules. The increased energy demand of inflammatory cuffs and damaged neural cells explains the strong angiogenic response in plaques and surrounding white matter. An angiogenic response has also been documented in an experimental model of MS, experimental allergic encephalomyelitis (EAE), where blood-brain barrier disruption and vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF naturally enhances neuron resistance to injury and regulates neural progenitor proliferation, migration, differentiation and oligodendrocyte precursor cell (OPC) survival and migration to demyelinated lesions. Angiogenesis, neurogenesis and oligodendroglia maturation are closely intertwined in the neurovascular niches of the subventricular zone, one of the preferential locations of inflammatory lesions in MS, and in all the other temporary vascular niches where the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis, induced either by CNS inflammation or by hypoxic stimuli related to neurovascular uncoupling, appears to be ineffective in chronic MS due to a counterbalancing effect of vasoconstrictive mechanisms determined by the reduced axonal activity, astrocyte dysfunction, microglia secretion of free radical species and mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic factors, should be promoted in therapeutic neuroregeneration efforts to combat the progressive, degenerative phase of MS.

Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

“…Identified up‐regulated gene transcripts determined by microarray (Illumina HumanRef‐8, v3.0; Illumina, Inc., San Diego, CA, USA) analysis after overexpression of microRNA‐155 (using 30 nM pre‐microRNA‐155) in hCMEC/D3 cells (14). Analysis was performed by using DAVID Bioinformatics ( https://david.ncifcrf.org) (98). All genes with a small but significant fold change in mRNA levels (>;1.17‐fold increase) were included in the analysis above; analysis from 3 independent biological replicates.…”

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

“…In some studies, the association of axon guidance with a group of proteins such as MET, plexin C1 (PLXNC1) and neuropilin-1 (NRP1) in NDP and semaphorin 5A (SEMA5A), EPHA4 and NTNG2 in RP has been reported [67,[73][74][75], showing active axons-related events in RP. Notch and HTLV-1 infection signalling pathways were two important pathways observed in both NDP and RP groups.…”

Imag(in)ing multiple sclerosis: Time to take better pictures

“…We might be able to characterize the perivenular topography of MS plaques in far greater detail than we have done previously using an advanced segmented echo-planar imaging readout scheme (21). Such visualization might be diagnostically useful (22), or potentially related to perivascular inflammatory cuff formation (23), but perhaps with improved detection we might even see the neovascularization that can support smoldering inflammation or even nascent repair at the lesion edge (24,25). …”