Article

Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats

International Center, for Spinal Cord Injury, Hugo Moser Research Institute, Department of Neurology, Johns Hopkins School of Medicine and Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Experimental Neurology (Impact Factor: 4.7). 04/2010; 222(2):211-8. DOI: 10.1016/j.expneurol.2009.12.029
Source: PubMed

ABSTRACT

Functional electrical stimulation (FES) can restore control and offset atrophy to muscles after neurological injury. However, FES has not been considered as a method for enhancing CNS regeneration. This paper demonstrates that FES dramatically enhanced progenitor cell birth in the spinal cord of rats with a chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb movement was implanted into these rats. Twelve identically-injured rats received inactive FES implants. An additional control group of uninjured rats were also examined. Ten days after FES implantation, dividing cells were marked with bromodeoxyuridine (BrdU). The "cell birth" subgroup (half the animals in each group) was sacrificed immediately after completion of BrdU administration, and the "cell survival" subgroup was sacrificed 7 days later. In the injured "cell birth" subgroup, FES induced an 82-86% increase in cell birth in the lumbar spinal cord. In the injured "cell survival" subgroup, the increased lumbar newborn cell counts persisted. FES doubled the proportion of the newly-born cells which expressed nestin and other markers suggestive of tripotential progenitors. In uninjured rats, FES had no effect on cell birth/survival. This report suggests that controlled electrical activation of the CNS may enhance spontaneous regeneration after neurological injuries.

Download full-text

Full-text

Available from: Warren M Grill
  • Source
    • "These limitations have impelled research workers to explore optimized and feasible protocols for NSC-based therapies. Numerous studies have revealed that the ES plays a potential regenerative role in memory (Liu et al., 2015a), depression (Zhang et al., 2014), stroke (Guo et al., 2014), and spinal cord injury (SCI) (Becker et al., 2010) in rat models. These findings may deepen our understanding of cell replacement therapies following CNS insults and then drive the translation of NSC therapies combined with ES from animal experiments into the clinic settings. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Researchers are enthusiastically concerned about neural stem cell (NSC) therapy in a wide array of diseases, including stroke, neurodegenerative disease, spinal cord injury, and depression. Although enormous evidences have demonstrated that neurobehavioral improvement may benefit from NSC-supporting regeneration in animal models, approaches to endogenous and transplanted NSCs are blocked by hurdles of migration, proliferation, maturation, and integration of NSCs. Electrical stimulation (ES) may be a selective non-drug approach for mobilizing NSCs in the central nervous system. This technique is suitable for clinical application, because it is well established and its potential complications are manageable. Here, we provide a comprehensive review of the emerging positive role of different electrical cues in regulating NSC biology in vitro and in vivo, as well as biomaterial-based and chemical stimulation of NSCs. In the future, ES combined with stem cell therapy or other cues probably becomes an approach for promoting brain repair.
    Full-text · Article · Nov 2015 · Frontiers in Human Neuroscience
  • Source
    • "This is in contrast to other ESTIM-based work that, for example, delivered constant stimulation over the course of the experiment (Ishibashi et al. 2006). This distinction may be clinically relevant as functional electrical stimulation in discrete times frames (e.g., 1 h/day) promotes aspects of regeneration following experimental spinal cord injury and is administered clinically to patients with spinal cord injury (Becker et al. 2010; Sadowsky and McDonald 2009). This system will be useful in future studies that require platforms to selectively treat neurons with simultaneous assessment of axon/glia interaction, particularly when long duration culture is required. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Axon demyelination contributes to the loss of sensory and motor function following injury or disease in the central nervous system. Numerous reports have demonstrated that myelination can be achieved in neuron/oligodendrocyte co-cultures. However, the ability to selectively treat neuron or oligodendrocyte (OL) cell bodies in co-cultures improves the value of these systems when designing mechanism-based therapeutics. We have developed a microfluidic-based compartmentalized culture system to achieve segregation of neuron and OL cell bodies while simultaneously allowing the formation of myelin sheaths. Our microfluidic platform allows for a high replicate number, minimal leakage, and high flexibility. Using a custom built lid, fit with platinum electrodes for electrical stimulation (10-Hz pulses at a constant 3 V with ~190 kΩ impedance), we employed the microfluidic platform to achieve activity-dependent myelin segment formation. Electrical stimulation of dorsal root ganglia resulted in a fivefold increase in the number of myelinated segments/mm² when compared to unstimulated controls (19.6 ± 3.0 vs. 3.6 ± 2.3 MBP+ segments/mm²). This work describes the modification of a microfluidic, multi-chamber system so that electrical stimulation can be used to achieve increased levels of myelination while maintaining control of the cell culture microenvironment.
    Full-text · Article · Apr 2012 · Neuromolecular medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Here, a robust tuner is presented that has been developed for support of early visual understanding by a robotic humanoid, sg1, under development. One of the achieved goals is to speed up the process of real-time segmentation by eliminating any tuning sessions from the online process and carrying them out offline. Effectiveness values (credits) assigned to stereo-based range findings and colour components (red, green, blue) are some of the tuned parameters. However, more than nine parameters (such as: stereo range finder search area, minimum and maximum size of regions, thresholds...) are tuned using a genetic algorithm. A novel idea for automatic evaluation of the region-edge segmentation has been applied as well.
    No preview · Conference Paper · Jan 2004
Show more