Repetitive spinal electromagnetic stimulation opens a window of synaptic plasticity in 1 damaged spinal cord : role of NMDA receptors

25 As we previously reported, propagation of action potentials through surviving axons are 26 dramatically impaired, resulting in reduced transmission to lumbar motoneurons after mid27 thoracic lateral hemisection (HX) in rats. The aim of the present study was to evoke action 28 potentials through the spared fibers using non-invasive electromagnetic stimulation (EMS) over 29 intact T2 vertebrae in an attempt to activate synaptic inputs to lumbar motoneurons and thus to 30 enhance plasticity of spinal neural circuits after HX. We found that EMS was able to activate 31 synaptic inputs to lumbar motoneurons and motor-evoked potentials (MEP) in hindlimb muscles 32 in adult anesthetized rats. Amplitude of MEP was attenuated in parallel with decline of responses 33 recorded from motoneurons pool after HX. Repetitive EMS (50 min, 0.2 Hz) facilitated the 34 amplitudes of responses elicited by electric stimulation of lateral white matter or dorsal 35 corticospinal tracts in HX rats. Facilitation sustained for at least 1.5 hours after termination of 36 EMS. The NMDA receptor blocker MK-801, injected intraspinally close to the recording 37 electrode prior to EMS, did not alter these responses, but blocked the EMS-induced facilitation, 38 suggesting that activation of NMDA receptors is required to initiate EMS-evoked increase. 39 When MK-801 was administered after EMS-induced facilitation was established, it induced 40 depression of these elevated responses. Results suggest that repetitive EMS over intact vertebrae 41 could be used as a therapeutic approach to open a window of synaptic plasticity after incomplete 42 mid-thoracic injuries: i.e. to activate NMDA receptors in lumbar motoneurons pool at synaptic 43 inputs and to strengthen transmission in damaged spinal cord. 44 45