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

Daniel Becker; Devin S. Gary; Ephron S. Rosenzweig; Warren M. Grill; John W. McDonald

doi:10.1016/j.expneurol.2009.12.029

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

Daniel Becker, Devin S. Gary, Ephron S. Rosenzweig, Warren M. Grill, John W. McDonald

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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.

Original language	English (US)
Pages (from-to)	211-218
Number of pages	8
Journal	Experimental Neurology
Volume	222
Issue number	2
DOIs	https://doi.org/10.1016/j.expneurol.2009.12.029
State	Published - Apr 2010
Externally published	Yes

Keywords

Cell birth
Exercise
Neural activity
Regeneration
Rehabilitation
Spinal cord injury
Stem cell

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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10.1016/j.expneurol.2009.12.029

Cite this

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title = "Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats",

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.",

keywords = "Cell birth, Exercise, Neural activity, Regeneration, Rehabilitation, Spinal cord injury, Stem cell",

author = "Daniel Becker and Gary, {Devin S.} and Rosenzweig, {Ephron S.} and Grill, {Warren M.} and McDonald, {John W.}",

note = "Funding Information: We thank L. Sage and D. Lenihan for editorial assistance, B. Jones for animal care, and A. Hansen for animal care and tissue processing. Supported by grants from the Barnes-Jewish Hospital and Barnes-Jewish Hospital Auxiliary Foundations (St. Louis MO), Washington University School of Medicine (St. Louis, MO), Sam Schmidt Foundation (Las Vegas, NV), the Jack Orchard and ALS Hope Foundations (St. Louis, MO), and NIH NINDS NS 45023 , 40520 , 39577 (JWM), State of Maryland Department of Health and Mental Hygiene Spinal Cord Injury Grant FHA077 - 002 (JWM), as well as the Johnson & Johnson Focused Giving Program (WMG). Appendix A Supplement Figure 1: FES had no effect on overall cell density as measured by Hoechst labeling. Hoechst 33342 labeled cells were counted at six levels in coronal spinal cord sections using stereological methods (optical fractionator). There was no difference demonstrated between groups or spinal levels. Supplement Figure 2: FES had no effect in the uninjured spinal cord. (A) Schematic diagram of the 15-day experimental design in animals that did not receive SCI. FES activation, timing, and BrdU labeling was identical to the animals that received SCI. (B) BrdU-labeled cells were counted at six levels in coronal spinal cord sections using stereological methods (optical fractionator). There was no difference demonstrated between groups or spinal levels. Appendix A ",

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doi = "10.1016/j.expneurol.2009.12.029",

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AU - Becker, Daniel

AU - Gary, Devin S.

AU - Rosenzweig, Ephron S.

AU - Grill, Warren M.

AU - McDonald, John W.

N1 - Funding Information: We thank L. Sage and D. Lenihan for editorial assistance, B. Jones for animal care, and A. Hansen for animal care and tissue processing. Supported by grants from the Barnes-Jewish Hospital and Barnes-Jewish Hospital Auxiliary Foundations (St. Louis MO), Washington University School of Medicine (St. Louis, MO), Sam Schmidt Foundation (Las Vegas, NV), the Jack Orchard and ALS Hope Foundations (St. Louis, MO), and NIH NINDS NS 45023 , 40520 , 39577 (JWM), State of Maryland Department of Health and Mental Hygiene Spinal Cord Injury Grant FHA077 - 002 (JWM), as well as the Johnson & Johnson Focused Giving Program (WMG). Appendix A Supplement Figure 1: FES had no effect on overall cell density as measured by Hoechst labeling. Hoechst 33342 labeled cells were counted at six levels in coronal spinal cord sections using stereological methods (optical fractionator). There was no difference demonstrated between groups or spinal levels. Supplement Figure 2: FES had no effect in the uninjured spinal cord. (A) Schematic diagram of the 15-day experimental design in animals that did not receive SCI. FES activation, timing, and BrdU labeling was identical to the animals that received SCI. (B) BrdU-labeled cells were counted at six levels in coronal spinal cord sections using stereological methods (optical fractionator). There was no difference demonstrated between groups or spinal levels. Appendix A

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N2 - 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.

AB - 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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KW - Exercise

KW - Neural activity

KW - Regeneration

KW - Rehabilitation

KW - Spinal cord injury

KW - Stem cell

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

Abstract

Keywords

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