Cerebral vasoconstriction after subarachnoid hemorrhage--role of changes in vascular receptor phenotype.
The pathological constriction of cerebral arteries known as cerebral vasospasm (CVS) is with a delay of 4 to 10 days linked to subarachnoid hemorrhage. Several agents have been suggested as being responsible; amongst these perhaps 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) are the most prominent given their ability to elicit powerful constriction of cerebral arteries. Investigating both 5-HT and ET receptors we have observed that there are distinct changes in receptor phenotype after experimental SAH, namely upregulation of the ETB and 5-HT1B receptors, and that this upregulation is linked to a higher sensitivity to the endogenous agonists. It has also been shown that reduction in regional cerebral blood flow (CBF) is associated with receptor upregulation and interventional animal experiments have shown a benefit from inhibiting the PKC and MAP kinase pathways on receptor upregulation, CBF and neurological outcome.
Hansen-Schwartz
Jacob
J
Dept. of Neurosurgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. jacob.schwartz@dadlnet.dk
Ansar
Saema
S
Edvinsson
Lars
L
D000818:Animals; D002536:Cerebral Arteries / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods; D010641:Phenotype; D014176:Protein Biosynthesis; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014158:Transcription, Genetic; D020301:Vasospasm, Intracranial / Q000150:complications*
D011985:Receptors, Serotonin