{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T21:40:12Z","timestamp":1679262012098},"reference-count":36,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1993,6]]},"abstract":"<jats:p content-type=\"fine-print\">\u2713 The effects of differing strategies of serotonergic manipulation on vascular permeability, prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) synthesis, and the clinical course are evaluated in an experimental model of neoplastic spinal cord compression in rats. Serotonergic manipulations include <jats:italic>in vivo<\/jats:italic> inhibition of serotonin (5-HT) synthesis by p-chlorophenylalanine (p-CPA) and <jats:italic>in vivo<\/jats:italic> blockage of serotonin type 2 (5-HT<jats:sub>2<\/jats:sub>) 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% \u00b1 5.1% (mean \u00b1 standard deviation) and reduces the elevated 5-HIAA:5-HT ratio to the normal value. The increased synthesis of PGE<jats:sub>2<\/jats:sub> 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<jats:sub>2<\/jats:sub> receptors mediate some of the deleterious vascular consequences observed in the compressed spinal cord by a mechanism not coupled with PGE<jats:sub>2<\/jats:sub> synthesis. A potential benefit of serotonergic manipulations for the acute treatment of neoplastic spinal cord compression is suggested.<\/jats:p>","DOI":"10.3171\/jns.1993.78.6.0929","type":"journal-article","created":{"date-parts":[[2009,5,27]],"date-time":"2009-05-27T14:58:28Z","timestamp":1243436308000},"page":"929-937","source":"Crossref","is-referenced-by-count":4,"title":["Serotonergic manipulations in experimental neoplastic spinal cord compression"],"prefix":"10.3171","volume":"78","author":[{"given":"Tali","family":"Siegal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzony","family":"Siegal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Neuropeptides","first-page":"269","article-title":"Potentiation of motoneuron excitability by combined administration of 5-HT agonist and TRH analogue.","volume":"6","author":"Clarke","year":"1985"},{"key":"b2","series-title":"Proc Natl Acad Sci USA","first-page":"7134","article-title":"Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor.","volume":"78","author":"Coughlin","year":"1981"},{"key":"b3","series-title":"Thromb Res","first-page":"321","article-title":"Platelet-mediated vascular permeability in the rat: a predominant role for 5-hydroxytryptamine.","volume":"38","author":"De Clerck","year":"1985"},{"key":"b4","series-title":"Circ Res","first-page":"143","article-title":"Pharmacological analysis of 5-hydroxytryptamine receptors in isolated intracranial and extracranial vessels of cat and man.","volume":"42","author":"Edvinsson","year":"1977"},{"key":"b5","series-title":"Annu Rev Pharmacol Toxicol","first-page":"307","article-title":"Subtypes of receptors for serotonin.","volume":"30","author":"Frazer","year":"1990"},{"key":"b6","series-title":"Brain Res","first-page":"263","article-title":"Contribution of serotonin neurons to the functional recovery after spinal cord injury in rats.","volume":"539","author":"Hashimoto","year":"1991"},{"key":"b7","series-title":"J Cardiovasc Pharmacol","first-page":"44","article-title":"Experience with ketanserin and ritanserin in hypertensive patients.","volume":"11","author":"Hedner","year":"1988"},{"key":"b8","series-title":"Serotonin and the Cardiovascular System.","first-page":"75","article-title":"Platelet activation and serotonin","author":"Holmsen","year":"1985"},{"key":"b9","series-title":"J Neurosurg","first-page":"203","article-title":"Edema and circulatory disturbance in the spinal cord compressed by epidural neoplasms in rabbits.","volume":"52","author":"Ikeda","year":"1980"},{"key":"b10","series-title":"Science","first-page":"889","article-title":"High-affinity uptake of serotonin into immunocytochemically identified astrocytes.","volume":"228","author":"Kimelberg","year":"1985"},{"key":"b11","series-title":"Neuropsychopharmacology","first-page":"361","article-title":"Gaps and peculiarities in 5-HT2 receptor studies.","volume":"3","author":"Leysen","year":"1990"},{"key":"b12","series-title":"Life Sci","first-page":"1015","article-title":"Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors.","volume":"28","author":"Leysen","year":"1981"},{"key":"b13","series-title":"J Neurotrauma","first-page":"219","article-title":"Norepinephrine and serotonin release upon impact injury to rat spinal cord.","volume":"7","author":"Liu","year":"1990"},{"key":"b14","series-title":"Serotonin Receptors.","first-page":"59","article-title":"Pharmacology and biochemistry of the 5-HT2 receptor","author":"Lyon","year":"1988"},{"key":"b15","series-title":"Brain Res","first-page":"15","article-title":"Autoradiographic mapping of 5-HT1, 5-HT1a, 5-HT1b and 5-HT2 receptors in the rat spinal cord.","volume":"550","author":"Marlier","year":"1991"},{"key":"b16","series-title":"J Neurol","first-page":"45","article-title":"5-HT2 receptor antagonists and migraine therapy.","volume":"238","author":"Mylecharane","year":"1991"},{"key":"b17","series-title":"J Neurosurg","first-page":"408","article-title":"Experimental effects of free serotonin on the brain and its relation to brain injury. 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