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


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.

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    • "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. "
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    • "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. "
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