Serotonin2 receptors mediate respiratory recovery after  cervical spinal cord hemisection in adult rats

The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO2 levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT2A/2C-receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO2 was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT2-receptor antagonist ketanserin but not with the 5-HT2C-receptor antagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

Download Full-text

5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.4.1528 ◽

2000 ◽

Vol 89 (4) ◽

pp. 1528-1536 ◽

Cited By ~ 38

Author(s):

Shi-Yi Zhou ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Phrenic Nerve ◽

Serotonin Receptor ◽

Cervical Spinal Cord ◽

Respiratory Drive ◽

Respiratory Pathway ◽

Cord Injury ◽

Respiratory Recovery ◽

Spinal Cord Hemisection

The present study investigates the role of serotonin in respiratory recovery after spinal cord injury. Experiments were conducted on C2 spinal cord hemisected, anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which end-tidal CO2 was monitored and maintained. Before drug administration, the phrenic nerve ipsilateral to hemisection showed no respiratory-related activity due to the disruption of the descending bulbospinal respiratory pathways by spinal cord hemisection. 5-Hydroxytryptophan (5-HTP), a serotonin precursor, was administrated intravenously. 5-HTP induced time- and dose-dependent increases in respiratory recovery in the phrenic nerve ipsilateral to hemisection. Although the 5-HTP-induced recovery was initially accompanied by an increase in activity in the contralateral phrenic nerve, suggesting an increase in descending respiratory drive, the recovery persisted well after activity in the contralateral nerve returned to predrug levels. 5-HTP-induced effects were reversed by a serotonin receptor antagonist, methysergide. Because experiments were conducted on animals subjected to C2 spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. In addition, the results also suggest that the maintenance of 5-HTP-induced respiratory recovery may not require a continuous enhancement of central respiratory drive.

Download Full-text

Spontaneous Functional Recovery in a Paralyzed Hemidiaphragm Following Upper Cervical Spinal Cord Injury in Adult Rats

Neurorehabilitation and Neural Repair ◽

10.1177/154596839901300404 ◽

1999 ◽

Vol 13 (4) ◽

pp. 225-234 ◽

Cited By ~ 90

Author(s):

Kwaku D. Nantwi ◽

Ashraf A. El-Bohy ◽

Gregory W. Schrimsher ◽

Paul J. Reier ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Cervical Spinal Cord ◽

Female Rats ◽

Adult Rats ◽

Cord Injury ◽

Upper Cervical ◽

Recording Conditions ◽

Bilateral Vagotomy ◽

Spinal Cord Hemisection

Previous studies have shown that latent respiratory pathways can be activated by as phyxia or systemic theophylline administration to restore function to a hemidiaphragm paralyzed by C2 spinal cord hemisection in adult female rats. Based on this premise, electrophysiologic recording techniques were employed in the present investigation to first determine qualitatively whether latent respiratory pathways are activated spon taneously following prolonged post hemisection periods (4-16 weeks) without any therapeutic intervention. Our second objective in a separate group of hemisected an imals was to quantitate any documented functional recovery under the following stan dardized recording conditions: bilateral vagotomy, paralysis with pancuronium bro mide, artificial ventilation, and constant PCO 2 (maintained at 25 mmHg).

Download Full-text