The Roy–Sherrington hypothesis: facts and surmises

Abstract

The 110-year-old metabolic hypothesis of Roy and Sherrington cannot fully explain the increases of cerebral blood flow (CBF) during increased functional activity of the central neurons. CBF may increase (a) much faster than the accumulation of the metabolic end products, (b) out of proportion to metabolic demands, (c) without significant change in local metabolism. The tight coupling of neuronal activity and blood flow in the brain is demonstrated by a large amount of data. Perivascular nerve endings were identified in the outer smooth muscle layer of the pial and intraparenchymal vessels. Their axon terminals contain a large variety of neurotransmitters, often co-localized in synaptic vesicles. Stimulation of the nerves results in a release of transmitters into the 80–100-nm neuromuscular synaptic clefts, and their specific receptors were identified in the vessel wall. There is ample evidence to suggest that neurogenic stimuli via perivascular nerve endings may act as rapid initiators, inducing a moment-to-moment dynamic adjustment of CBF to the metabolic demands, and further maintenance of these adjusted parameters is ensured by the metabolic and chemical factors. The significance of the perivascular nerves in the regulation of the cerebral blood flow, however, is either underestimated or completely neglected in the majority of textbooks for both medical students and clinicians. Since the regulatory role of the nervous system in the cerebrovascular bed has been fully appreciated among investigators in the last decades, revision of this antiquated view of the common medical knowledge is urgent.