Neuroangiogenesis

Neuroangiogenesis is a term used to describe the coordinated growth of nerves and blood vessels.[1] The nervous and blood vessel systems share guidance cues and cell-surface receptors allowing for this synchronised growth. This term only came into use in 2002[2] and the process was previously known as neurovascular patterning. The combination of neurogenesis and angiogenesis is an essential part of embryonic development and early life.[3] It is thought to have a role in pathologies such as endometriosis[4] and Alzheimer's disease.[5]

Physiology

Neurovascular patterning

Neurovascular development is the parallel emergence and patterning of the nervous system and the vascular system during embryogenesis and early life.[6] Neurovascular congruency appears to be determined by shared molecular patterning mechanism involving axon guidance that involves axonal guidance molecules such as sema3A (semaphorin 3A) and (neuropilin).[7]

Mechanisms

Neuroangiogenic and axonal guidance molecules act on both neuronal growth cones and endothelial tip cells in order to guide growth.

Neuronal growth cones are situated on the tips of nerve cells and are responsive to different factors, both positive and negative. Growth of the neuron occurs by an extension of the actin (red in image) and microtubule (green in image) cytoskeleton.[8]

Neuronal growth cone

Tip cells found at the extremity of the developing blood vessel control adjacent endothelial cells to direct growth. Tip cells have receptors and ligands via which they respond to local neuroangiogenic factors.[9]

Neurogenic factors

There are many neuroangiogenic factors, some of which act to promote neuronal growth and vice versa. The table shows examples

Neuroangiogenic factor Effect on neuron Effect on vascular endothelial cells Receptor/Ligand Origin
IGF-1 Promotion of neurogenesis and synaptogenesis EC proliferation, migration, and differentiation Ligand Liver cells
bFGF Proliferation of cortical progenitors and neurogenesis EC proliferation, migration, and differentiation Ligand Adipocytes
NGF Neuron survival, differentiation Promotion of angiogenesis and arteriogenesis in ischemic hindlimbs Ligand Multiple
Neuropilin Axon guidance Synergistic action of VEGF165 in EC migration and proliferation
Vascular development 		Receptor Target cell
VEGF Neuronal development and patterning, and has neurotrophic and neuroprotective effects Induces angiogenesis, promotes endothelial cell survival, proliferation and migration Ligand Multiple

Pathology

Neuroangiogenesis is implicated in a number of pathologies, including endometriosis[10] and senile dementias such as Alzheimer's disease.[11] Each of these incurs a significant cost for the healthcare industry, meaning that complete understanding of processes involved - including neuroangiogenesis - is necessary to enable development of functional treatments.[12]

Endometriosis

Endometriosis is a common gynaecological disease caused by endometrial tissue implanting outside the uterus, a common symptom of which is chronic pelvic pain. The formation, growth and persistence of these implants are dependent upon angiogenesis to increase the supply of blood vessels in these areas. The resulting increase in blood flow may correlate directly with pain symptoms. One possible explanation for this is the simultaneous growth of neurons into these areas alongside blood vessels through neuroangiogenesis.[13]

Alzheimer’s disease

A condition possibly related to a reduction in neuroangiogenic factors is Alzheimer’s disease. Without continued neuroangiogenesis, areas of the brain may no longer have the full complement of functional capillaries and hence, by inference, cognitive ability declines.[14]

References

  1. ↑ Greaves; et al. (October 2014). "Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3". Endocrinology 155: 4015–26. doi:10.1210/en.2014-1086. PMID 25051436. Retrieved 30 September 2015.
  2. ↑ Park; et al. (2002). "Delayed Up-regulation of Vascular Endothelial Growth Factor and flk-1 after Global Cerebral Ischemia in Mongolian Gerbil -Possible roles in neuroangiogenesis?" (PDF). Korean Neurological Association. Retrieved 30 September 2015.
  3. ↑ Bautch; et al. (2009). "Neurovascular Development: The beginning of a beautiful friendship". Cell Adhesion and Migration. Retrieved 30 September 2015.
  4. ↑ Asante; et al. (2011). "Endometriosis :The role of Neuroangiogenesis". Annual Review of Physiology 73: 163–182. doi:10.1146/annurev-physiol-012110-142158. Retrieved 30 September 2015.
  5. ↑ Ambrose, CT (2012). "Neuroangiogenesis: a vascular basis for Alzheimer's disease and cognitive decline during aging". Journal of Alzheimer's Disease 32: 773–88. doi:10.3233/JAD-2012-120067. PMID 22850316. Retrieved 30 September 2015.
  6. ↑ Bautch, Victoria L.; James, Jennifer M. "Special Focus: Angiogenesis in the Central Nervous System Neurovascular development The beginning of a beautiful friendship". Taylor and Francis Online. Retrieved 30 September 2015.
  7. ↑ Bates, Damien; Taylor, G. Ian; Minichiello, Joe; Farlie, Peter; Cichowitz, Adam; Watson, Nadine; Klagsbrun, Micheal; Mamluk, Roni; Newgreen, Donald F. "Neurovascular congruence results from a shared patterning mechanism that utilizes Semaphorin3A and Neuropilin-1". Retrieved 30 September 2015.
  8. ↑ Park, JA; Choi, KS; Kim, SY; Kim, KW. "Coordinated interaction of the vascular and nervous systems: from molecule to cell-based approaches". Research Gate. Retrieved 30 September 2015.
  9. ↑ Park, JA; Choi, KS; Kim, SY; Kim, KW. "Coordinated interaction of the vascular and nervous systems: from molecule to cell-based approaches". Research Gate. Retrieved 30 September 2015.
  10. ↑ Asante, A; Taylor, R N. "Endometriosis: the Role of Neuroangiogenesis". Annual Review of Physiology 73: 163–182. doi:10.1146/annurev-physiol-012110-142158.
  11. ↑ Ambrose, C T (2015). "A Therapeutic Approach for Senile Dementias: Neuroangiogenesis". Journal of Alzheimer's Disease 43 (1): 1–17.
  12. ↑ Morotti, M; Vincent, K; Brawn, J; Zondervan, K T; Becker, C M (2014). "Peripheral Changes in Endometriosis-Associated Pain". Human Reproduction Update 20 (5): 717–736. doi:10.1093/humupd/dmu021.
  13. ↑ Asante, A; Taylor, R N. "Endometriosis: the Role of Neuroangiogenesis". Annual Review of Physiology 73: 163–182. doi:10.1146/annurev-physiol-012110-142158.
  14. ↑ Ambrose, C T. "Alzheimer's Disease: the Great Morbidity of the 21st Century". American Scientist 101 (3): 194–201.
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