Regulation of brain microcirculation

Increase in brain activity is tightly linked to the circulation, and local stimulation of neurones triggers a rapid increase in local blood flow. This phenomenon, known as functional hyperaemia, was discovered by Sherrington in 1890. Functional hyperaemia is a local phenomenon as vasodilatation occurs in small vessels within ~200-250 ^m from the site of increased neuronal activity. Mechanisms of functional hyperaemia remained enigmatic for a long time; several hypotheses highlighted the role of local release of vasoactive factors, local innervation, or activation of nitric-oxide synthase and generation of NO. Recently, however, the crucial role of astroglia in control of microcirculation was identified.

The notion that astroglial cells provide a metabolic connection between neurones and blood vessels was initially made by Camillo Golgi in the 1870s. Recent advances in in situ cellular imaging have clearly demonstrated that astroglial Ca2+ signals triggered by neuronal activity enter endfeet and initiate the release of vasoactive substances, which in turn affect the tone of small arterioles enwrapped by these endfeet. Inhibition of astroglial Ca2+ signalling inhibits the functional link between neuronal activation and changes in vascular tone. In fact, astrocytes are able to provide dual control over the neighbouring blood vessels: they may either induce vasodilatation or vasoconstriction. Interestingly both effects begin with Ca2+ elevation in the endfeet and the release of arachidonic acid (AA). The latter can be transformed into prostaglandin derivatives by cyclo-oxygenase (COX), which can be blocked by aspirin; these derivatives of AA effectively relax the vascular muscle cells and cause vasodilatation and increased blood flow.

Brain Microcirculation

Postsynaptic neurone]

Figure 7.6 Model for astroglial-dependent regulation of local blood flow - astroglial cells couple neuronal activity with local circulation by releasing vasoconstrictors and vasodilators: Glutamate released at synapses during increased neuronal activity activates calcium signals in astrocytic processes enwrapping synaptic contacts. Calcium signals propagate through the astroglial cell (and astroglial syncytium) to reach the perivascular endfoot, where Ca2+ triggers the release of arachidonic acid (AA). Depending on the brain region and local enzymatic systems, AA can be converted to vasodilatatory prostaglandins (PG) by cyclo-oxygenase (COX), or to a vasoconstrictive agent 20 hydroxyeicosatetraenois acid (2-HETE), by a cytochrome P450 epoxygenase of the arteriole smooth muscle

Postsynaptic neurone]

Figure 7.6 Model for astroglial-dependent regulation of local blood flow - astroglial cells couple neuronal activity with local circulation by releasing vasoconstrictors and vasodilators: Glutamate released at synapses during increased neuronal activity activates calcium signals in astrocytic processes enwrapping synaptic contacts. Calcium signals propagate through the astroglial cell (and astroglial syncytium) to reach the perivascular endfoot, where Ca2+ triggers the release of arachidonic acid (AA). Depending on the brain region and local enzymatic systems, AA can be converted to vasodilatatory prostaglandins (PG) by cyclo-oxygenase (COX), or to a vasoconstrictive agent 20 hydroxyeicosatetraenois acid (2-HETE), by a cytochrome P450 epoxygenase of the arteriole smooth muscle

Alternatively, AA can be converted into the vasoconstrictive agent 20 hydroxyeicosatetraenois acid (2-HETE) by a cytochrome 450 enzyme residing in the arteriole smooth muscle (Figure 7.6).

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