Recovery of inspiratory intercostal muscle activity following high cervical hemisection

Abstract

Anatomical and neurophysiological evidence indicates that thoracic interneurons can serve a commissural function and activate contralateral motoneurons. Accordingly, we hypothesized that respiratory-related intercostal (IC) muscle electromyogram (EMG) activity would be only modestly impaired by a unilateral cervical spinal cord injury. Inspiratory tidal volume (VT) was recorded using pneumotachography and EMG activity was recorded bilaterally from the 1st to 2nd intercostal space in anesthetized, spontaneously breathing rats. Studies were conducted at 1–3 days, 2 wks or 8 wks following C2 spinal cord hemisection (C2HS). Data were collected during baseline breathing and a brief respiratory challenge (7% CO₂). A substantial reduction in inspiratory intercostal EMG bursting ipsilateral to the lesion was observed at 1–3 days post-C2HS. However, a time-dependent return of activity occurred such that by 2 wks post-injury inspiratory intercostal EMG bursts ipsilateral to the lesion were similar to age-matched, uninjured controls. The increases in ipsilateral intercostal EMG activity occurred in parallel with increases in VT following the injury (R = 0.55; P < 0.001). We conclude that plasticity occurring within a “crossed-intercostal” circuitry enables a robust, spontaneous recovery of ipsilateral intercostal activity following C2HS in rats.

Introduction

Following unilateral spinal cord hemisection at the second cervical segment (C2HS), plasticity in phrenic motor pathways results in a modest return of inspiratory activity in the ipsilateral hemi-diaphragm (Fuller et al., 2008) often termed the “crossed-phrenic phenomenon” (Goshgarian, 2009, Lane et al., 2009). However, the contribution of the crossed phrenic phenomenon to tidal volume (VT) appears to plateau by 2-wks post-injury in spontaneously breathing rats (Dougherty et al., 2012). The relatively small contribution of ipsilateral phrenic activity suggests that other motor outputs are critical to maintaining VT after chronic C2HS. For example, the contralateral hemi-diaphragm shows an increase in activity following unilateral diaphragm paralysis (Golder et al., 2001, Katagiri et al., 1994, Miyata et al., 1995, Rowley et al., 2005, Teitelbaum et al., 1993). This increase in contralateral phrenic output occurs very rapidly, and has been attributed to removal of inhibitory inputs from both large and small diameter phrenic afferents (Teitelbaum et al., 1993). Immediate and sustained increases in contralateral hemi-diaphragm activity probably sustain VT in the short term, but also may limit the ability of the contralateral phrenic motor pool to facilitate progressive (i.e., weeks–months) increases in VT after chronic spinal cord injury (Doperalski and Fuller, 2006, Fuller et al., 2006). In this scenario, time-dependent increases in the output of the accessory inspiratory muscles, such as the external intercostals (IC) (De Troyer et al., 2005), may be the primary contributor to any spontaneous increases in VT that may occur after the initial days–weeks following C2HS.

The thoracic spinal cord contains an extensive population of propriospinal interneurons that receive respiratory-related synaptic inputs (Kirkwood et al., 1984, Qin et al., 2002, Saywell et al., 2011). An increasing body of evidence suggests that these cells are ideal candidates to serve as a “synaptic relay” of inspiratory drive to intercostal motoneurons following partial interruption of bulbospinal respiratory pathways (Saywell et al., 2011). For example, a recent study found that thoracic interneurons with inspiratory discharge patterns almost always have an axonal projection extending across the spinal midline (Saywell et al., 2011). This anatomical feature is consistent with neurophysiological evidence (Kirkwood et al., 1988) that thoracic interneurons can modulate respiratory motoneuron output in the contralateral spinal cord. Thus, both anatomical and neurophysiological data suggest that thoracic interneurons can relay respiratory synaptic drive across the spinal midline. Accordingly, our primary purpose was to test the hypothesis that unilateral high cervical spinal cord injury (i.e., C2HS) would only modestly impair the inspiratory-related electromyogram (EMG) recorded in the ipsilateral intercostal muscles during spontaneous breathing in rats. Our secondary purpose was to explore the temporal relationship between the amplitude of ipsilateral IC EMG activity and inspiratory VT over the days–weeks following C2HS injury. Since the ipsilateral hemi-diaphragm makes only a modest contribution to VT following chronic C2HS (Dougherty et al., 2012, Fuller et al., 2008), we reasoned that the intercostal muscles are making a substantial contribution to the respiratory recovery process.