Functional Electrical Stimulation and the Modulation of the Axon Regeneration Program

Neural injury often leads to persistent functional deficits because spontaneous repair in the peripheral nervous system (PNS) is often incomplete, and endogenous repair mechanisms in the central nervous system (CNS) are negligible. Electrical stimulation supports axon growth in both central and peripheral neurons and represents a therapeutically viable approach to support neural repair and recovery. The development of clinical strategies employing electrical stimulation will depend upon determining the underlying mechanisms of activity-dependent axon regeneration and the heterogeneity of neuronal subtype responses to stimulation.

• 1
  Electrical stimulation of peripheral nerves elicits a retrograde calcium signal, which can be visualized in vivo using genetically encoded calcium indicators.
• 2
  Neuronal activity can activate growth-associated molecular pathways, such as the mTOR pathway, inactivation of PTEN, and increased phosphorylation of ribosomal protein S6.
• 3
  Chronic electrical stimulation drives collateral sprouting from intact descending corticospinal circuits, promoting sprouting of the corticospinal tract across the midline into the ipsilateral, denervated spinal cord.