Short-term cortical stimulation combined with targeted rehabilitation and Chondroitinase ABC improves upper limb function following a cervical contusion injury

Abstract

Spinal cord injuries (SCI) at the cervical level can lead to permanent upper limb and hand motor impairments, thus restoring upper limb function is amongst the highest priorities for SCI patients and can have extensive effects on improving quality of life and patient independence. We previously showed that long-term cortical stimulation of the motor cortex (10 weeks) when applied in conjunction with a daily upper limb targeted rehabilitation regiment and a neuroplasticity enhancing therapy such as lentiviral Chondroitinase ABC (ChABC) can lead to an increase of muscle activity which was translated to restored skilled function after a clinically relevant contusion injury. Here, we investigate the effects of a short term cortical stimulation protocol as part of the same neurorehabilitation paradigm to asses its efficecy. Adult rats were implanted unilaterally with stimulating electrodes (contralaterally to the dominant forepaw as determined by skilled reaching) on the surface of the motor cortex and received a bilateral cervical (C5/C6) contusion injury to produce severe and long lasting forelimb motor deficits. Contused animals received acute intraspinal injections of the neuroplasticity promoting agent ChABC and 12 consecutives days of epidural electrical stimulation of the motor cortex along with daily targeted upper limb behavioural rehabilitation (Whishaw Window and Montoya staircase, 15 minutes for 5 days/week for 7 weeks) starting at 7 days post injury. Our results revealed marked improvements in the tasks specific for assessing upper limb dexterity. These were also corroborated by electrophysiological and anatomical evidence. Thus, we provide robust evidence that short term cortical epidural stimulation as part of a combinational neurorehabilitation paradigm can restore upper limb function after a cervical contusion.