Respiratory recovery following high cervical hemisection

Abstract

In this paper we review respiratory recovery following C2 spinal cord hemisection (C2HS) and introduce evidence for ipsilateral (IL) and contralateral (CL) phrenic motor neuron (PhrMN) synchrony post-C2HS. Rats have rapid, shallow breathing after C2HS but ventilation ( logical or (E)) is maintained. logical or (E) deficits occur during hypercapnic challenge reflecting reduced tidal volume (VT), but modest recovery occurs by 12 wks post-injury. IL PhrMN activity recovers in a time-dependent manner after C2HS, and neuroanatomical evidence suggests that this may involve both mono- and polysynaptic pathways. Accordingly, we used cross-correlation to examine IL and CL PhrMN synchrony after C2HS. Uninjured rats showed correlogram peaks consistent with synchronous activity and common synaptic input. Correlogram peaks were absent at 2 wks post-C2HS, but by 12 wks 50% of rats showed peaks occurring with a 1.1+/-0.19ms lag from zero on the abscissa. These data are consistent with prolonged conduction time to IL (vs. CL) PhrMNs and the possibility of polysynaptic inputs to IL PhrMNs after chronic C2HS.

Figure 1. Representative histological sections of the cervical spinal cord following hemilesion

Panel A presents both longitudinal and transverse sections of a anatomically complete C2HMx injury. Panel B provides longitudinal and transverse sections of an incomplete C2HMx with ventromedial tissue sparing. The arrow in panel B indicates the area of midline tissue sparing. The longitudinal sections (40μm, vibratome) are labeled with antibodies to pseudo-rabies virus (PRV; as part of a separate study); the transverse sections (40μm, vibratome) are stained with luxol fast blue and cresyl voilet. Scale bars are 1mm.

Figure 2. Examples of phrenic neurograms and correlograms

Panel A presents phrenic neurograms recorded both ipsilateral and contralateral to C2HMx lesion at 2 (middle) and12 (bottom) wks post-injury. Bilateral phrenic bursting in an uninjured rat is shown in the top traces of Panel A. Time and amplitude scaling are identical in each trace; phrenic signals were amplified 1000x. Panel B shows an expanded time scale of the phrenic burst area indicated by the gray line in panel A. In addition, the event markers generated via spike2 software to enable cross-correlation (see methods) are presented immediately above or below the corresponding neurogram signal. Panel C shows correlograms generated via cross-correlation of phrenic event markers (see methods). The number of counts is shown on the Y-axes. In panel C, the top correlograms (i.e. Ci, Ciii and Cv) were generated from the complete record (i.e. ∼ 3 hr of data) associated with the phrenic data depicted in panel A. The bottom correlograms in panel C (i.e. Cii, Civ, Cvi) are provided as additional representative examples. While correlogram peaks were always observed in uninjured rats (Ci, Cii), they were never observed at 2 wks post-C2HMx (Ciii, Civ) and occurred in 50% of rats (6/12) at 12 wks post-C2HMx (Cv, Cvi). The arrow in panel Cvi indicates the presence of a peak occurring with a negative lag (see results).