title: Serotonin in the regulation of brain microcirculation.
abstract: Manipulation of brainstem serotonin (5-HT) raphe neurons induces significant alterations in local cerebral metabolism and perfusion. The vascular consequences of intracerebrally released 5-HT point to a major vasoconstrictor role, resulting in cerebral blood flow (CBF) decreases in several brain regions such as the neocortex. However, vasodilatations, as well as changes in blood-brain barrier (BBB) permeability, which are blocked by 5-HT receptor antagonists also can be observed. A lack of relationship between the changes in flow and metabolism indicates uncoupling between the two variables and is suggestive of a direct neurogenic control by brain intrinsic 5-HT neurons on the microvascular bed. In line with these functional data are the close associations that exist between 5-HT neurons and the microarterioles, capillaries and perivascular astrocytes of various regions but more intimately and/or more frequently so in those where CBF is altered significantly following manipulation of 5-HT neurons. The ability of the microvascular bed to respond directly to intracerebrally released 5-HT is underscored by the expression of distinct 5-HT receptors in the various cellular compartments of the microvascular bed. Thus, it appears that while some 5-HT-mediated microvascular functions involve directly the blood vessel wall, others would be relayed through the perivascular astrocyte. The strategic localization of perivascular astrocytes and the different 5-HT receptors that they harbor strongly emphasize their putative pivotal role in transmitting information between 5-HT neurons and microvessels. It is concluded that the cerebral circulation has full capacity to adequately and locally adapt brain perfusion to changes in central 5-HT neurotransmission either directly or indirectly via the neuronal-astrocytic-vascular tripartite functional unit. Dysfunctions in these neurovascular interactions might result in perfusion deficits and might be involved in specific pathological conditions.
authors.affiliation: Laboratory of Cerebrovascular Research, Montréal Neurological Institute, McGill University, Québec, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Cohen
authors.forename: G
authors.initials: G
authors.lastname: Bonvento
authors.forename: P
authors.initials: P
authors.lastname: Lacombe
authors.forename: E
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D006801:Humans; D008833:Microcirculation / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
chemical_list: D012701:Serotonin