Changes in blood-brain barrier and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats.
Plasma serotonin (5-HT) was elevated by an intravenous infusion of this amine into urethane-anaesthetized rats and the concentration approximated that present in various neurological diseases and mental abnormalities. An infusion of 10 micrograms per kg body weight for 10 min significantly increased blood-brain barrier (BBB) permeability to Evans blue and 131I-sodium measured in whole brain. Regional BBB determinations with labelled 131I-sodium showed that the permeability to this compound was increased in the cerebral cortex, hippocampus, caudate nucleus, hypothalamus, colliculus and the cerebellum but not in the pons and the medulla oblongata. Regional blood flow was reduced in the same parts which showed BBB abnormality tested with 125I-labeled microspheres. Pretreatment with cyproheptadine, a 5-HT2 receptor antagonist, prevented the BBB increase and the regional blood flow was near normal values. Similar effects were obtained with indomethacin, a prostaglandin synthesis inhibitor. Vinblastine, known to influence vesicular transport, eliminated extravasation of the tracers but the regional blood flow remained depressed. A hypothesis is put forward that serotonin after binding to its receptor in the cerebral vessels stimulates prostaglandin which either directly or by means of cyclic adenosine monophosphate causes an increased vesicular transport across the endothelial cells and thus an extravasation of tracer substances in the brain. Obviously, this form of exudation can be influenced by pharmacological means.
Sharma
H S
HS
Laboratory of Neuropathology, Institute of Pathology, University Hospital, Uppsala, Sweden.
Olsson
Y
Y
Dey
P K
PK
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003533:Cyproheptadine / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D011453:Prostaglandins; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D012701:Serotonin; D007213:Indomethacin