Digital Theses Archive


Tesi etd-09282018-134309

Type of thesis
Chemogenetic and neurotechnology approaches for the recovery of motor function after paralysis following stroke and spinal cord injury
Scientific disciplinary sector
INGEGNERIA - Biorobotics
relatore Prof. MICERA, SILVESTRO
  • chemogenetic
  • epidural electrical stimulation
  • neuromodulation
  • neuroplasticity
  • rehabilitation
  • serotonin
  • spinal cord injury
  • stroke
Exam session start date
Stroke and spinal cord injury are two of the main causes of paralysis worldwide. Both conditions induce abrupt impairments with devastating consequences for the quality of life of patients. Despite significant progress in the development of rehabilitation strategies, existing treatments provide variable outcomes and can restore only limited limb mobility.<br>After an injury of the central nervous system, limited restoration of motor functions occurs spontaneously during a narrow post-injury time window through neuroplasticity. Exploiting neuroplasticity is a key aspect for developing more effective rehabilitative treatments. In this thesis, I present two novel approaches for neuromodulation of neural plasticity after a lesion of the central nervous system.<br>In the first part of the thesis, we define a combined post-stroke rehabilitation protocol involving robotic training and stimulation of serotonergic signaling, specifically via the 1A receptor in a chemogenetic mouse model. Our results highlighted a synergistic effect of this combination of robot-aided rehabilitation and pharmacological intervention. Mice treated with the combined treatment showed improved motor function and these motor improvements generalized to untrained motor tasks. Remarkably, this combined treatment also restored pre-lesion movement patterns, avoiding the development of maladaptive and compensatory behaviours. To investigate the clinical viability of this method, we used robotic training with a clinically approved drug to activate the serotonin 1A receptor in wild type mice. Again, we observed improved motor functions after stroke, indicating a path for clinical translation.<br>In the second part of this thesis, my colleagues and I evaluated an electrical approach to augment plasticity after a cervical spinal cord injury in non-human primates. Epidural electrical stimulation (EES) of the spinal cord has been shown to reactivate spinal circuits below a lesion and enable the generation of motor activity. Recent studies show its efficacy in restoration of cyclical locomotion after thoracic spinal cord injury. We thus investigated whether EES could also be used for restoration of the more complex upper-limb movements, namely three-dimensional reaching and grasping after a cervical spinal cord injury. Preliminary results of this work are promising: we were able to modulate arm movements in healthy animals and even elicit some reaching in a spinally lesioned animal. <br>Both the approaches proposed in this thesis could be applied to clinical trials. Indeed, they could even be applied together to develop future strategies able to improve the results of neurorehabilitation. <br>