SEROTONIN IN THE REGULATION OF BRAIN MICROCIRCULATION

Manipulation of brainstem serotonin (5-HT) raphe neurons induces signi ficant alterations in local cerebral metabolism and perfusion. The vas cular consequences of intracerebrally released 5-HT point to a major v asoconstrictor role, resulting in cerebral blood flow (CBF) decreases in several brain regions such as the neocortex. However, vasodilatatio ns, as well as changes in blood-brain barrier (BBB) permeability, whic h are blocked by 5-HT receptor antagonists also can be observed. A lac k of relationship between the changes in flow and metabolism indicates uncoupling between the two variables and is suggestive of a direct ne urogenic control by brain intrinsic 5-HT neurons on the microvascular bed. In line with these functional data are the close associations tha t 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 followi ng 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 com partments 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 pivot al role in transmitting information between 5-HT neurons and microvess els. Iris 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-as trocytic-vascular tripartite Functional unit. Dysfunctions in these ne urovascular interactions might result in perfusion deficits and might be involved in specific pathological conditions. Copyright (C) 1996 El sevier Science Ltd.