Modest spontaneous recovery of ventilation following chronic high cervical hemisection in rats

• Published in: Experimental neurology 2008-05, Vol.211 (1), p.97-106
• Main Authors: Fuller, D.D., Doperalski, N.J., Dougherty, B.J., Sandhu, M.S., Bolser, D.C., Reier, P.J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Blood Gas Analysis; Cervical Plexus - pathology; Crossed phrenic phenomenon; Disease Models, Animal; Functional Laterality; Hypercapnia - etiology; Hypercapnia - physiopathology; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Motoneurons; Motor Neurons - physiology; Neurology; Phrenic; Plasticity; Plethysmography; Pulmonary Ventilation; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Time Factors; Traumas. Diseases due to physical agents
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2008.01.013

Following C2 spinal hemisection (C2HS) in adult rats, ipsilateral phrenic motoneuron (PhMN) recovery occurs through a time-dependent activation of latent, crossed-spinal collaterals ( i.e., spontaneous crossed phrenic phenomenon; sCPP) from contralateral bulbospinal axons. Ventilation is maintained during quiet breathing after C2HS, but the ability to increase ventilation during a respiratory stimulation ( e.g. hypercapnia) is impaired. We hypothesized that long-term expression of the sCPP would correspond to a progressive normalization in ventilatory patterns during respiratory challenge. Breathing was assessed via plethsymography in unanesthetized animals and phrenic motor output was measured in urethane-anesthetized, paralyzed and vagotomized rats. At 2-week post-C2HS, minute ventilation (VE) was maintained during baseline (room air) conditions as expected but was substantially blunted during hypercapnic challenge (68 ± 3% of VE in uninjured, weight-matched rats). However, by 12 weeks the spinal-lesioned rats achieved a hypercapnic VE response that was 85 ± 7% of control ( p = 0.017 vs. 2 wks). These rats also exhibited augmented breaths (AB's) or “sighs” more frequently ( p < 0.05) than controls; however, total AB volume was significantly less than control at 2- and 12-week post-injury (69 ± 4% and 80 ± 5%, p < 0.05, respectively). We also noted that phrenic neurograms demonstrated a consistent delay in onset of the ipsilateral vs. contralateral inspiratory phrenic burst at 2–12-week post-injury. Finally, the ipsilateral phrenic response to respiratory challenge (hypoxia) was greater, though not normalized, at 4–12- vs. 2-week post-injury. We conclude that recovery of ventilation deficits occurs over 2–12-week post-C2HS; however, intrinsic neuroplasticity remains insufficient to concurrently restore a normal level of ipsilateral phrenic output.