Brain‐derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide‐dependent contributor of brain‐derived neurotrophic factor in the brain

Abstract

These data reveal that BDNF levels measured in brain homogenates correspond for a large part to BDNF present in cerebral endothelial cells and that cerebrovascular BDNF production is dependent on cerebrovascular endothelial eNOS activity. They provide a paradigm shift in the cellular source of brain BDNF and suggest a new approach to improve our understanding of the link between endothelial function and cognition.

The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory

“…Endothelium‐derived nitric oxide contributes to synaptic plasticity and long‐term potentiation in the brain, in part because the blood vessel endothelium, in the presence of active (phosphorylated) eNOS, releases BDNF into the brain . Indeed, the blood vessel endothelium is a major source of cerebral BDNF, with endothelial cells producing BDNF at 50 times the rate of neurons . In turn, BDNF may enhance vasodilation and the release of nitric oxide in a positive feedback loop .…”

“…Indeed, the blood vessel endothelium is a major source of cerebral BDNF, with endothelial cells producing BDNF at 50 times the rate of neurons . In turn, BDNF may enhance vasodilation and the release of nitric oxide in a positive feedback loop . Thus, the paradigm that migraines are an integrated neurovascular phenomenon extends to neural protection and repair.…”

“…For example, PAF stimulates the release of BDNF and serotonin from platelets and increases production of nitric oxide by the endothelium, which in turn raises production of BDNF. BDNF then furthers the production of nitric oxide in a positive feedback loop . CGRP and substance P may stimulate eNOS and increase the production of nitric oxide .…”

Neuromodulation by cerebrovasculature BDNF: is it much greater than we think?

“…The study by Monnier et al . () provides further support of the vasculature as a neuromodulator and the strong link that exists between the endothelium and neurones.…”

“…The findings published by Monnier et al . () in this journal showing substantial cerebrovascular BDNF synthesis are very interesting and could change our way we perceive BDNF production in the brain under normal and disease states. BDNF is one of the classic neurotrophins first discovered in the 1950s and acts on TrkB and pan75 neurotrophin receptor (p75 NTR ) receptors.…”