Cerebral circulatory and metabolic effects of 5‐hydroxytryptamine in anesthetized baboons.

Abstract

1. The cerebral circulatory effects of the intracarotid administration of 5-hydroxytryptamine were examined in anaesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe technique, cerebral O2 consumption and glucose uptake were measured as indices of brain metabolism and electrocortical activity was continuously monitored. 2. Despite a marked reduction in the calibre of the internal carotid artery (assessed angiographically), the intracarotid infusion of 5-hydroxytryptamine 0-1 microgram/kg. min did not effect any significant changes in cerebral blood flow, O2 consumption or glucose uptake. 3. Following transient osmotic disruption of the blood-brain barrier with the intracarotid infusion of hypertonic urea, the same dose of 5-hydroxytryptamine effected a marked reduction in cerebral blood flow from 51 +/- 2 to 36 +/- 2 ml./100 g. min (mean +/- S.E.; P less than 0-01). Both indices of cerebral metabolism were reduced significantly and the e.e.g. showed a more pronounced suppression-burst pattern. 4. We postulate that the cerebral circulatory responses to 5-hydroxytryptamine are dependent upon the integrity of the blood-brain barrier and the predominant effect of the intravascular administration of 5-hydroxytryptamine is on cortical activity or metabolism, rather than on cerebrovascular smooth muscle.

Study of platelet-mediated neurotoxicity in rat brain.

“…In our previous studies relating to the effect of platelet products on the neurons of spinal explants, we had quantified by morphometric techniques the number and the size distribution of neurons in the ventral horns. We found, as reported by Delfs et al, 10 that >90% of the neurons in the ventral horns, both in the treated and control groups, were <500 fim 2 , and the major portion of this was in 100-200 /im 2 range. Although the number of neurons per ventral horn in the explants varied depending on the age of the animal, spinal level, and duration in culture before the experiment, these were strictly controlled for within each experiment.…”

“…1 Among them, serotonin has been convincingly shown to suppress central nervous system function. 2 Arterial thrombi, a major cause of cerebral infarction, consist largely of platelets, constituting >50% by volume. This platelet concentration in thrombi amounts to 190 times the concentration in whole blood.…”

Enhanced Cerebrovascular Responsiveness to Hypercapnia following Depletion of Central Serotonergic Terminals

“…Numerous studies have shown 5-HT to be a po tent cerebrovascular constrictor, both in vitro (Toda et aI., 1976;Forster and Whalley, 1982;Fu and Toda, 1983) and in situ (Edvinsson et aI., 1977). Although these studies examined large cerebral ar teries and pial arterioles, following circumvention of the blood-brain barrier, 5-HT administered sys temically produces reductions in CBF in the whole animal (Harper and MacKenzie, 1977;Grome and Harper, 1983), which would be consistent with there being a similar serotonergic constrictor influ ence upon the resistance vessels. More recently, pharmacological inhibition of endogenous 5-HT re lease, by systemic application of an agonist specific for the 5-HT1A autoreceptor, was found to induce increases in LCBF that were in excess of any con comitant changes in LCMRglc in the physiologically normal rat (McBean et aI., 1991).…”

Nigral-Induced Decrease in Striatal Blood Flow and the Influence on This Decrease of Several Drugs in Reserpinized and Non-Reserpinized Cats

“…There are several reports in vivo (17)(18)(19)(20) and in vitro (21)(22)(23)(24) that 5-HT caused a direct vasoconstriction and that this vaso constriction was attenuated by methysergide, so the experiments in reserpinized cats were carried out in order to further examine the effects of dopamine and serotonin on nigral induced decrease in striatal blood flow. It is well known that reserpine impairs the mechanism that stores catecholamines and serotonin, and it reduces the content of these active substances (25,26 by the serotonergic pathway from the raphe nucleus (39).…”