Angiogenesis, Neurogenesis and Neuroplasticity in Ischemic Stroke

Abstract

Only very little is know about the neurovascular niche after cardioembolic stroke. Three processes implicated in neurorepair: angiogenesis, neurogenesis and synaptic plasticity, would be naturally produced in adult brains, but also could be stimulated through endogen neurorepair phenomena. Angiogenesis stimulation generates new vessels with the aim to increase collateral circulation. Neurogenesis is controlled by intrinsic genetic mechanisms and growth factors but also ambiental factors are important. The leading process of the migrating neural progenitor cells (NPCs) is closely associated with blood vessels, suggesting that this interaction provides directional guidance to the NPCs. These findings suggest that blood vessels play an important role as a scaffold for NPCs migration toward the damaged brain region. DNA microarray technology and blood genomic profiling in human stroke provided tools to investigate the expression of thousands of genes. Critical comparison of gene expression profiles after stroke in humans with those in animal models should lead to a better understanding of the pathophysiology of brain ischaemia. Probably the most important part of early recovery after stroke is limited capacity of penumbra/infarct neurones to recover. It became more clear in the last years, that penumbra is not just passively dying over time but it is also actively recovering. This initial plasticity in majority contributes towards later neurogenesis, angiogenesis and final recovery. Penumbra is a principal target in acute phase of stroke. Thus, the origin of newly formed vessels and the pathogenic role of neovascularization and neurogenesis are important unresolved issues in our understanding of the mechanisms after stroke. Biomaterials for promoting brain protection, repair and regeneration are new hot target. Recently developed biomaterials can enable and increase the target delivery of drugs or therapeutic proteins to the brain, allow cell or tissue transplants to be effectively delivered to the brain and help to rebuild damaged circuits. These new approaches are gaining clear importance because nanotechnology allows better control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration and outgrowth.

Obesity and cancer phenotype: Is angiogenesis a missed link?

“…Hypoxia and angiogenesis close relationship also plays an important role in the brains of patients who survived from stroke, being microvessel density correlated positively with survival. Increased synthesis of proangiogenic factors like FGF-2, PDGF and VEGF (and their receptors) is also seen in this context, corroborating the importance of angiogenesis in several ischemic conditions [94].…”

Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation

“…VEGF-A, which induces angiogenesis, also appears to support neurogenesis (Fabel, et al, 2003,Font, et al, 2010,Jin, et al, 2002). We previously found that in young mice, both supra-lactate threshold exercise and lactate itself induced brain VEGF-A gene expression (E, et al, 2013b).…”

Three-dimensional visualization of rat brain microvasculature following permanent focal ischaemia by synchrotron radiation

“…22,23 Furthermore, following permanent occlusion of the MCA, endothelial cells surrounding the infarcted area have been observed to initiate proliferation as early as 12-24 h post infarct. 24 Correspondingly, an increase in vessel density was observed in the peri-infarcted region 3 days after the ischaemic insult.…”