Neurogenic Regulation of Cerebral Blood Flow

The brain has a well-developed vascular network that allows it to consume up to 15% of cardiac output at its low weight relative to the whole-body weight. Normally, metabolic demands of the brain depend considerably on the intensity of functioning of its different regions, which requires a continuous local blood flow regulation. On the other hand, the state of systemic hemodynamics exert a significant impact on the organ blood flow. Complex and multilevel regulatory mechanisms of cerebral blood flow are aimed at minimizing possible adverse effects of systemic hemodynamic disorders. The importance of a precise and prompt cerebral blood flow regulation is reinforced by the lack of energy reserves or substrates for autonomous energy production in nervous tissue. The major mechanisms of cerebral blood flow regulation include myogenic regulation, local exposures to systemic blood flow humoral factors and vasoactive substances (hormones, metabolites), changes in blood gas composition (rises and falls in blood oxygen or carbon dioxide tension). Moreover, there are endothelium-dependent regulatory mechanisms. Yet another level of cerebrovascular tone regulation is represented by the impact of neurotransmitters released from vasomotor nerve terminals of sympathetic and parasympathetic divisions of the autonomic nervous system, as well as from synaptic endings of subcortical neurons and cortical interneurons. The present review addresses the principles of neurogenic regulation of cerebral blood flow. Neurogenic vascular tone regulation is the most complex regulatory circuit. The autonomic cerebrovascular innervation has significant features that distinguish it from that in most other organs of the great circle of blood circulation. Apart from autonomic innervation as such, brain vessels receive sensory inputs, while small intracerebral arterioles are additionally innervated directly by the neurons of subcortical nuclei and by cortical interneurons. Therefore, a deeper insight into the molecular mechanisms of cerebral blood flow neurogenic regulation may serve as a basis for the development of new neuromodulation-based therapeutic approaches to severe brain diseases.