Reorganization of Respiratory Descending Pathways following Cervical Spinal Partial Section Investigated by Transcranial Magnetic Stimulation in the Rat

Abstract

High cervical spinal cord injuries lead to permanent respiratory deficits. One preclinical model of respiratory insufficiency in adult rats is the C2 partial injury which causes unilateral diaphragm paralysis. This model allows the investigation of a particular population of respiratory bulbospinal axons which cross the midline at C3-C6 spinal segment, namely the crossed phrenic pathway. Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to study supraspinal descending respiratory pathways in the rat. Interestingly, a lateral C2 injury does not affect the amplitude and latency of the largest motor-evoked potential recorded from the diaphragm (MEPdia) ipsilateral to the injury in response to a single TMS pulse, compared to a sham animal. Although the rhythmic respiratory activity on the contralateral diaphragm is preserved at 7 days post-injury, no diaphragm activity can be recorded on the injured side. However, a profound reorganization of the MEPdia evoked by TMS can be observed. The MEPdia is reduced on the non-injured rather than the injured side. This suggests an increase in ipsilateral phrenic motoneurons excitability. Moreover, correlations between MEPdia amplitude and spontaneous contralateral diaphragmatic activity were observed. The larger diaphragm activity correlated with a larger MEPdia on the injured side, and a smaller MEPdia on the non-injured side. This suggests, for the first time, the occurrence of a functional neuroplasticity process involving changes in motoneuron excitability balance between the injured and non-injured sides at a short post-lesional delay.

Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies

“…In the few studies investigating magnetically induced MEPs in animal models, there has been a great variation in anesthetic choice. These range from inhalants such as isoflurane and halothane ( Luft et al, 2002 ; Deffeyes et al, 2015 ; Vinit et al, 2016 ), and injectable anesthetics such as sodium pentobarbital ( Rotenberg et al, 2010 ; Vahabzadeh-Hagh et al, 2011 ), and xylazine/zoletil ( Hsieh et al, 2015 ). All anesthetics are known to impact on neuronal function to varying degrees, with their exact mechanisms of action altering how this impact manifests ( Angel and Gratton, 1982 ; Anis et al, 1983 ; Simons et al, 1992 ; Lahti et al, 1999 ; Antkowiak, 2002 ; Antunes et al, 2003 ).…”

Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

“…TMS can also be used to assess excitability and plasticity of phrenic motoneurons post-SCI via non-invasively accessing supraspinal respiratory centers. For example, we have demonstrated early functional neuroplasticity with TMS in the absence of spontaneous functional diaphragm activity on the injured side in a C2Hx rat (Vinit et al 2016). More specifically, TMS was used to stimulate supraspinal structures, inducing action potential volleys which may travel via spared bulbospinal pathways (contralateral to injury), eliciting diaphragmatic motor evoked potentials on the injured, paralyzed, side of the diaphragm.…”

“…This technique utilizes a brief, highly intense magnetic field applied to cortical and sub-cortical areas to elicit volleys of action potentials which propagate from supraspinal levels to their muscular targets. A number of clinical studies have demonstrated TMS to be an effective way of generating diaphragmatic motor evoked potentials (Davey et al, 1996; Khedr and Trakhan, 2001; Lissens and Vanderstraeten, 1996) and may be a safe, non-invasive, and readily usable strategy for neuromodulation and treatment of respiratory dysfunction post-SCI (Vinit et al, 2016; Vinit et al, 2014). While supraspinal neuromodulation (e.g.…”

Supraspinal respiratory plasticity following acute cervical spinal cord injury

“…Given that some brainstem neurons remain connected to spinal circuitry following partial SCI and appear to be involved with functional neuroplastic changes even acutely post-injury, they represent an unexplored therapeutic target. Recent studies by Vinit et al (Vinit et al, 2016; 2014) using transcranial magnetic stimulation in the adult rat revealed that activity within brainstem pathways can not only be activated, but may be therapeutically targeted (Vinit et al, 2016; Vinit et al, 2014). …”