Neural And Vascular Interactions Regulate Brain Blood Vessel Growth

Blood flow – and the vasculature which enables this – is of critical importance to most tissues and organs of the body. The health and stability of vasculature in the brain is particularly crucial to general health and cognition, with the brain consuming 20% of cardiac output despite only making up 2% of the body’s overall weight.

The unit which integrates the neural and vascular cellular compartments of the brain is aptly named the neurovascular unit.

The interactions between vasculature and brain cells (neurons and glial) are extremely important, with a mutually beneficial relationship to the neurovascular unit. This is apparent in previous research, where vascular cells have been shown to affect and regulate neural cell growth (neurogenesis) and cell function; whilst the inverse interaction, of neural on vascular cells has also been shown to affect vascular stability and growth (angiogenesis).

However, the interactions between neural cells to promote vascular angiogenesis has been investigated to a lesser extent.

This has recently been addressed in a multi-institute research study, where the groups have established that neural cells have a significant impact on blood vessels within the brain. The research, published in Brain Structure and Function, investigates the cellular and molecular interactions in the neurovascular unit between neural and vascular cells.

Neural Progenitor Cell Proportion

The researchers established that a reduced proportion of growing neural progenitor cells (neural stem cells) has a negative effect on angiogenesis and induced blood vessel withdrawal. These neural cells have been shown previously to produce vascular endothelial growth factor (VEGF – protein), which is crucial to both neurogenesis and angiogenesis within the brain.

The reduction in neural cells correlated with a reduced measurement of VEGF-A (a specific type of VEGF produced by these cells), and is likely to contribute to the vascular instability and reduced angiogenesis observed in this study.

Limitations

The group used a transgenic mouse model to investigate this, where the mutated gene reduced the proportion of neural progenitor cells within the brain. Although the information gained from this study is very important and supports previous findings in the research area, further investigation is required to fully understand the role of VEGF in relation to angiogenesis from interactions with neural cells.

Also, the use of an animal model does not guarantee that the results observed in this study will be translatable to human brains; although the research gives us a very interesting insight into the functions of the brain and the neurovascular unit.

Applications

This study exemplifies the need for cell to cell crosstalk within the neurovascular unit, both during development, and in matured adult tissue. The interactions within this tissue are important for stabilisation, growth and maintenance of neural and vascular cells.

In relation to neurovascular diseases this research paves the way for a novel treatment strategy. A therapeutic approach which aims to upregulate VEGF signalling to promote both neurogenesis and angiogenesis after damage from stroke or from vascular dementia related neurodegeneration could be utilised in future.

In addition, the neurogenic and angiogenic potential of VEGF could be utilised for tissue engineering and neurovascular unit modelling approaches. By integrating VEGF into tissue engineered neurovascular unit it is possible to promote these crucial processes and create the desired tissue more effectively for modelling or transplantation purposes.

Pombero A, Garcia-Lopez R, Estirado A, Martinez S
Vascular pattern of the dentate gyrus is regulated by neural progenitors
Brain Structure and Function. 2018 Jan 6. doi: 10.1007/s00429-017-1603-z

Author: Geoffrey Potjewyd; Regenerative Medicine & Neuroscience PhD student at the University of Manchester.

Image: Directed Differentiation Of Multipotential Human Neural Progenitor Cells. Credit: Carol N. Ibe And Eugene O. Major, National Institute of Neurological Disorders and Stroke (NINDS)