Serotonergic Response to Spinal Distraction Trauma in Experimental Scoliosis

Abstract

The effects of distraction injury to the spinal cord on serotonin (5HT) content and metabolism in a rat model of scoliosis were studied. Previous studies in this laboratory (Salzman et al., 1987a) have identified the 5HT response as a major component of the posttraumatic progression of spinal injury after impact trauma in the rabbit. The present study was designed to determine the universality of this response by examining a different model of injury in a different species. The results demonstrate that distraction trauma in the rat, like impact injury in the rabbit, is associated with a rapid and robust increase in the local spinal cord content and metabolism of 5HT and a long-term depletion of 5HT below the site of injury. The roles of the blood platelet and the raphe-spinal tract in the acute response and the disruption of axoplasmic transport during the chronic phase of injury are discussed.

The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma

“…The results of these experiments demonstrate the therapeutic efficacy of mianserin treatment after experimental spinal cord injury (SCI) in the rat, and support the hypothesis that the acute elevation in spinal 5-HT concentration observed after trauma due to various causes in several species [16][17][18][19] AU intravenous doses of mianserin tested were associated with at least one sign of improvement, but only the l-mg/kg dosage was consistently accompanied by significant improvement for all measures. Thus, a single intravenous injection of 1 mgkg of mianserin at 15 minutes after a 50 gm cm spinal impact resulted in significantly improved final and cumulative Tarlov scores and Rivlin-Tator angleboard scores as well as preserved long-tract survival below the lesion.…”

A Model of Experimental Spinal Cord Trauma Based on Computer-Controlled Intervertebral Distraction: Characterization of Graded Injury

“…These results are consistent with previous biomechanical analyses of experimental [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and clinical spinal distraction 28,29 regarding the influence of distraction length on the viscoelastic properties of the vertebrae and surrounding musculoskeletal tissue. In previous studies of spinal distraction of the rat from the authors' laboratory, 9,11 the amount of force required to produce distraction lengths above 4 mm increased exponentially, whereas the ability of the spinous ligaments to undergo viscoelastic relaxation decreased proportionately. In the previous model, neurologic injury required mechanical failure of the vertebrae or ligaments at distraction lengths greater than 8 mm.…”

“…The skull was then exposed and implanted with stainless steel screw electrodes (Small Parts, Miami, FL) for the recording of somatosensory-evoked potentials (SEPs), as described previously. [7][8][9][10] The amplitude of the major negative wave (latency ϭ 16 -22 milliseconds) was recorded five times before the initial incision and one to three times after laminectomy, after the insertion of each sublaminar hook, and at 2, 5, 10, and 15 minutes after the application of distraction force. Only those animals that displayed a SEP with a stable latency and amplitude (coefficient of variation Ͻ5 and Ͻ10%, respectively, calculated as the standard deviation divided by the mean of five prior recordings) were subjected to further study.…”

“…The concentrations of serotonin (5-HT) and its major metabolite, 5-hydroxy-indole-3-acetic acid (5-HIAA), were determined by liquid chromatography with dual electrochemical detection as described previously. [7][8][9][10]13,[15][16][17][18] In addition to the determination of 5-HT and 5-HIAA concentrations in each segment, 5-HTDP and 5-HIAADP (the ratio of 5-HT or 5-HIAA content in T11/T9 distal/proximal to the injury site) were calculated to measure descending raphespinal axoplasmic transport and axon survival. The ratio of 5-HIAA/5-HT in each segment was used as a measure of serotonergic metabolism.…”

Pharmacological Approaches to Functional Recovery After Spinal Injury

“…The extent of the reduction correlated with the extent of locomotor dysfunction [78} (Hashimoto and Fukuda 1991). Reducing 5-HT levels further using the neurotoxin 5,7 dihydroxytryptamine significantly reduced recovery [78]. However, p-chlorophenylalanine, a competitive inhibitor of the 5-HT synthesis enzyme tryptophan hydroxylase, had no influence on the time course of recovery, despite further reducing 5-HT levels.…”