In:
Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 78, No. 6 ( 1993-06), p. 929-937
Kurzfassung:
✓ The effects of differing strategies of serotonergic manipulation on vascular permeability, prostaglandin E 2 (PGE 2 ) synthesis, and the clinical course are evaluated in an experimental model of neoplastic spinal cord compression in rats. Serotonergic manipulations include in vivo inhibition of serotonin (5-HT) synthesis by p-chlorophenylalanine (p-CPA) and in vivo blockage of serotonin type 2 (5-HT 2 ) receptors either by the selective antagonist ketanserin or by cyproheptadine. In paralyzed rats, the ratio of 5-hydroxyindole-3-acetic acid (5-HIAA) to 5-HT is significantly elevated in the compressed segments, suggesting that 5-HT utilization is increased. Treatment with p-CPA attenuates spinal 5-HT levels by 62.8% ± 5.1% (mean ± standard deviation) and reduces the elevated 5-HIAA:5-HT ratio to the normal value. The increased synthesis of PGE 2 observed in the compressed cord is unaffected by p-CPA or ketanserin treatment but is markedly attenuated by cyproheptadine. Ketanserin reduces the 10-fold increase in spinal cord permeability observed in paralyzed rats in a clearly dose-related manner. If given at the first sign of neurological dysfunction, ketanserin delays the onset of paraplegia with the 1-mg/kg dose being clearly superior. Cyproheptadine and p-CPA also reduce the increased permeability and protract the course to paraplegia. A comparison of the effect of dexamethasone, indomethacin, cyproheptadine, p-CPA, and ketanserin reveals that they protract the disease course by 48%, 57%, 60%, 64%, and 78%, respectively. These data suggest that 5-HT 2 receptors mediate some of the deleterious vascular consequences observed in the compressed spinal cord by a mechanism not coupled with PGE 2 synthesis. A potential benefit of serotonergic manipulations for the acute treatment of neoplastic spinal cord compression is suggested.
Materialart:
Online-Ressource
ISSN:
0022-3085
DOI:
10.3171/jns.1993.78.6.0929
Sprache:
Unbekannt
Verlag:
Journal of Neurosurgery Publishing Group (JNSPG)
Publikationsdatum:
1993
ZDB Id:
2026156-1
