Effects of serotonergic agents on respiratory recovery after cervical spinal injury

2015 ◽  
Vol 119 (10) ◽  
pp. 1075-1087 ◽  
Author(s):  
Shih-Hui Hsu ◽  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Serotonergic System ◽  
Chronic Injury ◽  
Adult Rats ◽  
Respiratory Impairment ◽  
Cord Injury ◽  
Cervical Spinal Injury

Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2laminectomy. A bolus intravenous injection of a serotonin precursor [5-hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury.

scholarly journals Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

2019 ◽  
Vol 126 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Breathing Patterns ◽  
Cord Injury ◽  
Spinal Contusion ◽  
Cervical Spinal Injury

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.

Impact of cervical spinal cord injury on the relationship between the metabolism and ventilation in rats

2021 ◽  
Author(s):  
Tzu-Ting Chiu ◽  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tidal Volume ◽  
Cervical Spinal Cord ◽  
Cervical Spinal Cord Injury ◽  
Male Rats ◽  
Whole Body ◽  
Post Injury ◽  
Chronic Injury ◽  
Cord Injury

Cervical spinal cord injury typically results in respiratory impairments. Clinical and animal studies have demonstrated that respiratory function can spontaneously and partially recover over time after injury. However, it remains unclear whether respiratory recovery is associated with alterations in metabolism. The present study was designed to comprehensively examine ventilation and metabolism in a rat model of spinal cord injury. Adult male rats received sham (i.e., laminectomy) or unilateral mid-cervical contusion injury (height of impact rod: 6.25 or 12.5 mm). Breathing patterns and whole-body metabolism (O2 consumption and CO2 production) were measured using a whole-body plethysmography system conjugated with flow controllers and gas analyzer at the acute (1 day post-injury), subchronic (2 weeks post-injury), and chronic (8 weeks post-injury) injury stages. The results demonstrated that mid-cervical contusion caused a significant reduction in the tidal volume. Although the tidal volume of contused animals can gradually recover, it remains lower than that of uninjured animals at the chronic injury stage. While O2 consumption and CO2 production were similar between uninjured and contused animals at the acute injury stage, these two metabolic parameters were significantly reduced in contused animals at the subchronic to chronic injury stages. Additionally, the relationships between ventilation, metabolism, and body temperature were altered by cervical spinal cord injury. These results suggest that cervical spinal cord injury causes a complicated reconfiguration of ventilation and metabolism that may enable injured animals to maintain a suitable homeostasis for adapting to the pathophysiological consequences of injury.

Respiratory motor outputs following unilateral midcervical spinal cord injury in the adult rat

2014 ◽  
Vol 116 (4) ◽  
pp. 395-405 ◽  
Author(s):  
Kun-Ze Lee ◽  
Yi-Jia Huang ◽  
I-Lun Tsai
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Whole Body ◽  
Adult Rats ◽  
Cord Injury ◽  
Burst Amplitude ◽  
Respiratory Recovery ◽  
The Impact

The present study was designed to investigate the impact of midcervical spinal cord injury on respiratory outputs and compare respiratory recovery following high- vs. midcervical spinal injury. A unilateral hemisection (Hx) in the spinal cord at C2 or C4 was performed in adult rats. Respiratory behaviors of unanesthetized animals were measured at normoxic baseline and hypercapnia by whole body plethysmography at 1 day and 1, 2, 4, and 8 wk after spinal injury. C2Hx and C4Hx induced a similar rapid shallow breathing pattern at 1 day postinjury. The respiratory frequency of C4Hx animals gradually returned to normal, but the tidal volume from 1 to 8 wk postinjury remained lower than that of the control animals. Linear regression analyses indicated that the tidal volume recovery was greater in the C4Hx animals than in the C2Hx animals at the baseline, but not at hypercapnia. The bilateral phrenic nerve activity was recorded in anesthetized animals under different respiratory drives at 8–9 wk postinjury. The phrenic burst amplitude ipsilateral to the lesion reduced following both high- and midcervical Hx; however, the ability to increase activity was lower in the C4Hx animals than in the C2Hx animals. When the data were normalized by the maximal inspiratory effort during asphyxia, the phrenic burst amplitude enhanced in the C4Hx animals, but reduced in the C2Hx animals compared with the control animals. These results suggest that respiratory deficits are evident following midcervical Hx, and that respiratory recovery and neuroplasticity of phrenic outputs are different following high- vs. midcervical spinal injury.

scholarly journals Tidal volume and diaphragm muscle activity in rats with cervical spinal cord injury

2015 ◽  
Vol 27 (3) ◽  
pp. 791-794 ◽  
Author(s):  
Hidetaka Imagita ◽  
Akira Nishikawa ◽  
Susumu Sakata ◽  
Yasue Nishii ◽  
Akira Minematsu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tidal Volume ◽  
Muscle Activity ◽  
Cervical Spinal Cord ◽  
Cervical Spinal Cord Injury ◽  
Diaphragm Muscle ◽  
Cord Injury

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

2001 ◽  
Vol 91 (6) ◽  
pp. 2665-2673 ◽  
Author(s):  
Shi-Yi Zhou ◽  
Gregory J. Basura ◽  
Harry G. Goshgarian
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Phrenic Nerve ◽  
Cervical Spinal Cord ◽  
Sprague Dawley ◽  
Related Activity ◽  
Adult Rats ◽  
Cord Injury ◽  
Respiratory Recovery ◽  
Spinal Cord Hemisection

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.

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