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1.  Intraspinal microstimulation for the recovery of function following spinal cord injury 
Progress in brain research  2011;194:227-239.
Spinal cord injury is a devastating neurological trauma, often resulting in the impairment of bladder, bowel, and sexual function as well as the loss of voluntary control of muscles innervated by spinal cord segments below the lesion site. Research is ongoing into several classes of therapies to restore lost function. These include the encouragement of neural sparing and regeneration of the affected tissue, and the intervention with pharmacological and rehabilitative means to improve function. This review will focus on the application of electrical current in the spinal cord in order to reactivate extant circuitry which coordinates and controls smooth and skeletal muscle below the injury. We first present a brief historical review of intraspinal microstimulation (ISMS) focusing on its use for restoring bladder function after spinal cord injury as well as its utilization as a research tool for mapping spinal cord circuits that coordinate movements. We then present a review of our own results related to the use of ISMS for restoring standing and walking movements after spinal cord injury. We discuss the mechanisms of action of ISMS and how they relate to observed functional outcomes in animal models. These include the activation of fibers-in-passage which lead to the transsynaptic spread of activation through the spinal cord and the ability of ISMS to produce fatigue-resistant, weight-bearing movements. We present our thoughts on the clinical potential for ISMS with regard to implantation techniques, stability, and damage induced by mechanical and electrical factors. We conclude by suggesting improvements in materials and techniques that are needed in preparation for a clinical proof-of-principle and review our current attempts to achieve these.
PMCID: PMC3245977  PMID: 21867807
Electrical stimulation; lumbosacral enlargement; locomotor networks; standing; walking; muscle fatigue
2.  The Effects of Intraspinal Microstimulation on Spinal Cord Tissue in the Rat 
Biomaterials  2010;31(21):5552-5563.
Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4 hours/day for 30 days. Functional measurements showed no change in force recruitment following transection and chronic ISMS, indicating no changes to underlying neural networks. The implantation of sham intraspinal microwires produced a spatially-limited increase in the density of microglia/macrophages and GFAP+ astrocytes adjacent to the microwire tracks, indicating a persistent immune response. Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48 nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2 ± 35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2 ± 38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue.
PMCID: PMC2875271  PMID: 20430436
3.  Muscle Plasticity in Rat Following Spinal Transection and Chronic Intraspinal Microstimulation 
Intraspinal microstimulation (ISMS) employs electrical stimulation of the ventral grey matter to reactivate paralyzed skeletal muscle. This work evaluated the transformations in the quadriceps muscle that occurred following complete transection and chronic stimulation with ISMS or a standard nerve cuff (NCS). Stimulation was applied for 30 days, 4 hours/day. Both methods induced significant increases in time-to-peak tension (ISMS 35%, NCS 25%) and ½ rise-time (ISMS 39%, NCS 25%) compared to intact controls (IC). Corresponding increases in type-IIA myosin heavy chain (MHC) and decreases in type-IID MHC were noted compared to IC. These results were unexpected because ISMS recruits motor units in a near-normal physiological order while NCS recruits motor units in a reversed order. Spinal cord transection and 30 days of stimulation did not alter either recruitment profile. The slope of the force recruitment curves obtained through ISMS following transection and 30 days of stimulation was similar to that obtained in intact animals, and 3.4-fold shallower than that obtained through NCS. The transformations observed in the current work are best explained by the near maximal level of motor unit recruitment, the total daily time of activity and the tonic nature of the stimulation paradigm.
PMCID: PMC3037113  PMID: 20813653
Functional electrical stimulation; muscle plasticity; spinal motoneurons

Results 1-3 (3)