title: Modest spontaneous recovery of ventilation following chronic high cervical hemisection in rats.
abstract: 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.
authors.affiliation: University of Florida, College of Health and Health Professions, Department of Physical Therapy, 100 Newell Drive, Gainesville, FL 32610, USA. dfuller@phhp.ufl.edu
authors.forename: D D
authors.initials: DD
authors.lastname: Fuller
authors.forename: N J
authors.initials: NJ
authors.lastname: Doperalski
authors.forename: B J
authors.initials: BJ
authors.lastname: Dougherty
authors.forename: M S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: D C
authors.initials: DC
authors.lastname: Bolser
authors.forename: P J
authors.initials: PJ
authors.lastname: Reier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D002572:Cervical Plexus / Q000473:pathology; D004195:Disease Models, Animal; D007839:Functional Laterality; D006935:Hypercapnia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D010991:Plethysmography; D012123:Pulmonary Ventilation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors