Perivascular Neurotransmitter Regulation of Cerebral Blood Flow

Introduction

The brain circulation is generally believed to be controlled by (1) chemical factors as perivascular pH; (2) autoregulation, a response to changes in systemic blood pressure; and (3) intrinsic mechanisms within the brain via neurovascular units and the microvasculature. However, for decades it has been known that the major cerebral arteries and arterioles are supplied by perivascular nerves with origin in the sympathetic, parasympathetic, and sensory ganglia . With start during the 1970s, development of new histochemical methods allowed the demonstration of neurotransmitters in nerve fibers, followed by detailed analysis of their possible roles in regulation of cerebral blood flow (CBF).

The early demonstration of autonomic nerves (noradrenaline, NA, and acetylcholine, ACh), receptors, and effects on CBF provided novel input. A fabulous development in peptide chemistry followed, providing isolation of gut peptides like vasoactive intestinal polypeptide (VIP). Technology made it possible to produce quantities of peptides that could be used in functional tests, localized with immunohistochemistry and quantified with radioimmunoassay (RIA). This allowed for a paradigm shift with the first demonstration of perivascular VIP-containing nerve fibers in the wall of cerebral arteries . The initial study led to a decade when a new perivascular neuropeptide was demonstrated almost every year followed by attempts to understand their respective role in regulation of CBF .

Nature of the Perivascular Nerves Innervating Intracranial Blood Vessels

It is well recognized that the cerebral arteries have a dense network of perivascular nerves mainly localized around the major arteries of the circle of Willis and pial vessels on the surface of the brain. These intracranial blood vessels are supplied with nerve fibers that emanate from cell bodies in ganglia belonging to the sympathetic, parasympathetic, and sensory nervous systems ( Fig. 13.1 ) . In addition, intracerebral arterioles and microvessels are mainly surrounded by astrocytes but may also be innervated by nerve fibers that originate within the brain itself and thereby representing an intrinsic nerve supply .