Year-end Sale % OFF 
Abstract
Following the discovery of the vasorelaxant properties of nitric oxide (NO) by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS) led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow (CBF). Anatomically, axons, dendrites, or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting CBF as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e., neuronal, glial, and vascular cells) also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.
Highlights
Nitric oxide (NO) is a small inorganic, labile gaseous molecule originally identified as endothelium-derived relaxing factor (EDRF) mediating relaxation of blood vessels (Furchgott and Zawadzki, 1980)
At a distance within 50 μm of the blood vessels, the percentage of GABAergic neuron subsets appears to be the following: 39% express vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY), 28% express NO synthase (NOS), 28% express SOM, some cells co-express more than one marker. This distribution differed considerably with their respective density in the same layers and fields of the somatosensory cortex, which was VIP (46.1%) > SOM (30.4%) > NPY (16.1%) > NOS (7.4%). These results indicate a privileged redistribution of NPY and NOS interneurons in the vicinity of cortical microvessels
This premise is supported by the following observations: (1) NO concentrations increase at the beginning of the stimulation and remain elevated during at least a 2 min duration of neuronal stimulation; (2) cerebral blood flow (CBF) responses to 1 s stimulation of the mouse hindpaw is reduced by about 50% in NO synthase in neurons (nNOS) knockout mice or after topical application of L-NA (Kitaura et al, 2007); (3) Topical application of L-NNA dampers the entire neurovascular coupling (NVC); (4) Systemic administration of 7-NI attenuates NVC during long stimulus of more than 60 s (Dirnagl et al, 1993, 1994; Ngai et al, 1995; Lindauer et al, 1999; Peng et al, 2004)
Summary
The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation. Axons, dendrites, or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Various experimental approaches support a role of neuronal NO in the maintenance of resting CBF as well as in the vascular response to neuronal activity. NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways involved in vascular control. Cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e., neuronal, glial, and vascular cells) known to produce NO. The role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
