Breakthroughs and Views
Coordinated interaction of the vascular and nervous systems: from molecule- to cell-based approaches

https://doi.org/10.1016/j.bbrc.2003.09.129Get rights and content

Abstract

Endothelial cells (ECs) build blood vessels and regulate their plasticity in coordination with neurons. Likewise, neurons construct nerves and regulate their circuits in coordination with ECs. Blood vessel/nerve interactions, ultimately, play essential roles for the neurovascular network and brain function. With conventional molecular approaches, such coordinated interaction is likely due to complex interplay of neuroangiogenic factors and receptors. Aside from molecular regulation of neuroangiogenic factors, currently, cell-based approaches to investigate how blood vessels (or nerves) respond to nerves (or blood vessels) appropriately in the pathophysiological situation are gradually emerging. In order to define responsiveness and flexibility of the neurovascular network in response to the local need, the intercellular communication and coordinated interaction between the vascular and nervous systems need to be thought as a working unit. Based on the scale of the working unit which is in the millimeter range with respect to the physical distance of the neurovascular network, we propose to use a rather conceptual term “Millibiology”. The millibiological approach for the coordinated interaction might bring us new paradigm to define neurovascular functions in the pathophysiological state.

Section snippets

Coordinated regulation of neuroangiogenic factors generated from blood vessels and nerves

In the developing embryo and adult, endothelial cells (ECs) and neuronal cells respond to changing environments through the production of growth factors and their receptors. The factors/receptors act as sensors of such environmental changes and transduce information into the inside of cells and finally induce proliferation, migration, and differentiation of ECs and neuronal cells. Thus, a great deal of research in angiogenesis and neurogenesis has been focused on neuroangiogenic factors and

Neurovascular coordination during angiogenesis and neurogenesis

In the adult brain, neurogenic activity usually persists in neuroproliferative regions, including the subgranular zone of hippocampal dentate gyrus (SGZ), ventricle zone (VZ), and olfactory bulb [29]. The neuroproliferative regions include precursors of neurons, glia, and ECs, which secrete neuroangiogenic factors and form neuroangiogenic niches for instructive signals [29]. Following brain injuries such as brain ischemia and degenerative neuronal diseases, the recovery of the damaged neurons

Perspectives: in resonance with the vascular and nervous systems

Much of the current research has been attempted to understand the molecular and intercellular events that coordinate blood vessels and nerves in the pathophysiological system. Blood vessels and nerves construct highly organized networks, respond appropriately to the local demand, and then execute brain functions through coordinated processes (Fig. 1). However, disruption of their resonance might lead to pathological states, such as brain ischemia, vascular dementia, aging brain, amyotrophic

Acknowledgements

This work was supported by the National Research Laboratory Fund (2000-N-NL-01-C-015) from the Ministry of Science and Technology, Korea (to K.-W. K.), and the Vascular System Research Center grant from the Korea Science and Engineering Foundation, Korea.

References (48)

  • D. Bates et al.

    The pattern of neurovascular development in the forelimb of the quail embryo

    Dev. Biol.

    (2002)
  • Y.S. Mukouyama et al.

    Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin

    Cell

    (2002)
  • D. Bates et al.

    Neurovascular congruence results from a shared patterning mechanism that utilizes Semaphorin3A and Neuropilin-1

    Dev. Biol.

    (2003)
  • O.O. Ogunshola et al.

    Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain

    Brain Res. Dev. Brain Res.

    (2000)
  • R.H. Adams et al.

    Eph receptors and ephrin ligands. Essential mediators of vascular development

    Trends Cardiovasc. Med.

    (2000)
  • V. Prevot et al.

    Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro–glio–endothelial interactions in gonadotropin-releasing hormone release

    Neuroscience

    (1999)
  • D.M. Araujo et al.

    Trophic effects of interleukin-4, -7 and -8 on hippocampal neuronal cultures: potential involvement of glial-derived factors

    Brain Res.

    (1993)
  • D. Malonek et al.

    Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation

    Proc. Natl. Acad. Sci. USA

    (1997)
  • M. Zonta et al.

    Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation

    Nat. Neurosci.

    (2003)
  • E.J. Yoder

    Modifications in astrocyte morphology and calcium signaling induced by a brain capillary endothelial cell line

    Glia

    (2002)
  • E.H. Lo et al.

    Mechanisms, challenges and opportunities in stroke

    Nat. Rev. Neurosci.

    (2003)
  • N.W. Gale et al.

    Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development

    Genes Dev.

    (1999)
  • K. Jin et al.

    Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo

    Proc. Natl. Acad. Sci. USA

    (2002)
  • S. Shigematsu et al.

    IGF-1 regulates migration and angiogenesis of human endothelial cells

    Endocrinol. J.

    (1999)
  • Cited by (81)

    • Interplay between angiogenesis and neurogenesis in nerve regeneration

      2022, Biomaterials for Vasculogenesis and Angiogenesis
    • Claudin-5a knockdown attenuates blood-neural barrier in zebrafish

      2021, Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
      Citation Excerpt :

      Moreover, we previously reported that A-kinase anchor protein 12 (AKAP12), a scaffold protein, regulates tight junction proteins in BNB formation during a critical period in brain development (Choi et al., 2007; Lee et al., 2003) and that AKAP12 was colocalized with cldn5a in the brain microvessels of zebrafish (data not shown). Further studies may reveal the regulatory mechanisms underlying the modulation of barrier properties via cell-to-cell connections of the neurovascular unit (Park et al., 2003). The present study also revealed a new role of cldn5a in zebrafish that has not been reported in other organisms, i.e., a role in BCB integrity.

    • Dementia: Paradigm shifting into high gear

      2019, Alzheimer's and Dementia
    • Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke

      2015, Experimental Neurology
      Citation Excerpt :

      Reactive astrocytes are required for functional recovery after stroke (Hayakawa et al., 2010) and indirectly contribute to post-ischemic angiogenesis , a hypoxic induced event (Liu et al., 2014a), through production of vascular endothelial growth factor (VEGF) (Zhang et al., 2002). Astrocytes reside in the cerebral side of the BBB increasing its strength (Park et al., 2003; Petty and Lo, 2002) even though their primary function is to restrict permeability of the BBB, accounting for maintenance of the integrity of the NVU (Igarashi et al., 1999; Janzer and Raff, 1987; Kondo et al., 1996; Willis et al., 2004) in the framework of ischemic stroke (del Zoppo and Mabuchi, 2003; Lo et al., 2003). Astrocytes are activated in response to preconditioning, and have an even greater activation during ischemia in preconditioned brains (Bacigaluppi et al., 2010; Biron et al., 1999).

    View all citing articles on Scopus
    View full text