Development of autonomic dysreflexia after spinal cord injury is associated with a lack of serotonergic axons in the intermediolateral cell column.

Abstract

Autonomic dysreflexia consistently develops in patients and in rats after severe upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal sympathetic excitation. In this study we induced episodic hypertension in rats after varying degrees of SCI severity to investigate the contribution of serotonergic bulbospinal axons to the development of autonomic dysreflexia after SCI. Female Wistar rats (250-300 g) were used in all experiments in the following groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). Immunohistochemistry for choline acetyl transferase and serotonin (5-HT) was performed on T8-T12 spinal segments to identify sympathetic preganglionic neurons, and to assess 5-HT-containing axons in the intermediolateral cell column (IMLC), respectively. Testing for autonomic dysreflexia was conducted by measuring mean arterial pressure (MAP) at rest and after colon distension-induced hypertension. We observed that the magnitude of the pressor response seen after colon distension correlated with SCI severity and density of 5-HT-immunoreactive axons in the IMLC. Intrathecal administration of the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin decreased resting MAP and was permissive to the colon distension-induced pressor response in SCI rats. These results suggest that the SCI-induced loss of serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that sparing of serotonergic axons beyond a critical threshold preserves cardiovascular regulation and prevents the development of autonomic dysreflexia.

• Authors: Christen M Cormier, Karim Mukhida, Greg Walker, Daniel R Marsh
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 27 Issue 10 Pg. 1805-18 (Oct 2010) ISSN: 1557-9042 [Electronic] United States
• PMID: 20698759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serotonin Antagonists
• Serotonin Receptor Agonists
• dimethoxy-4-indophenyl-2-aminopropane
• Serotonin
• Indophenol
• Ketanserin
• Choline O-Acetyltransferase

Topics

• Analysis of Variance
• Animals
• Autonomic Dysreflexia (etiology, metabolism, physiopathology)
• Axons (drug effects, metabolism)
• Blood Pressure (drug effects, physiology)
• Choline O-Acetyltransferase (metabolism)
• Female
• Heart Rate (drug effects, physiology)
• Immunohistochemistry
• Indophenol (analogs & derivatives, pharmacology)
• Injections, Spinal
• Ketanserin (pharmacology)
• Motor Activity (physiology)
• Rats
• Rats, Wistar
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Spinal Cord Injuries (complications, metabolism, physiopathology)