PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury

Research output: Contribution to journalComment/debate

25 Citations (Scopus)

Abstract

Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p<0.01) and relative Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56±0.01 vs. bpV: 0.64±0.02; p<0.05) and at the epicenter (Veh: 0.42±0.03 vs. bpV: 0.54±0.03; p<0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109±5.3 vs. Veh: 77±2.7mm-2; p<0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0±0.02 vs. Veh: 0.77±0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.

Original languageEnglish (US)
Pages (from-to)64-68
Number of pages5
JournalNeuroscience Letters
Volume573
DOIs
StatePublished - Jun 24 2014

Fingerprint

Oligodendroglia
Myelin Sheath
Spinal Cord Injuries
Atrophy
Motor Neurons
Axons
Cervical Cord
bisperoxovanadium
PTEN Phosphohydrolase
Therapeutics
Neurons
Forelimb
Contusions
Carisoprodol
Demyelinating Diseases
Phosphoric Monoester Hydrolases
Fluorescent Antibody Technique
Regeneration
Cell Survival
Staining and Labeling

Keywords

  • BpV
  • Neuron atrophy
  • Oligodendrocyte survival
  • PTEN
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

@article{da8deb64555f4a65bd66e2a859597d5f,
title = "PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury",
abstract = "Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30{\%}; p<0.01) and relative Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56±0.01 vs. bpV: 0.64±0.02; p<0.05) and at the epicenter (Veh: 0.42±0.03 vs. bpV: 0.54±0.03; p<0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109±5.3 vs. Veh: 77±2.7mm-2; p<0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0±0.02 vs. Veh: 0.77±0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.",
keywords = "BpV, Neuron atrophy, Oligodendrocyte survival, PTEN, Spinal cord injury",
author = "Walker, {Chandler L.} and Xu, {Xiao Ming}",
year = "2014",
month = "6",
day = "24",
doi = "10.1016/j.neulet.2014.02.039",
language = "English (US)",
volume = "573",
pages = "64--68",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury

AU - Walker, Chandler L.

AU - Xu, Xiao Ming

PY - 2014/6/24

Y1 - 2014/6/24

N2 - Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p<0.01) and relative Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56±0.01 vs. bpV: 0.64±0.02; p<0.05) and at the epicenter (Veh: 0.42±0.03 vs. bpV: 0.54±0.03; p<0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109±5.3 vs. Veh: 77±2.7mm-2; p<0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0±0.02 vs. Veh: 0.77±0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.

AB - Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p<0.01) and relative Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56±0.01 vs. bpV: 0.64±0.02; p<0.05) and at the epicenter (Veh: 0.42±0.03 vs. bpV: 0.54±0.03; p<0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109±5.3 vs. Veh: 77±2.7mm-2; p<0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0±0.02 vs. Veh: 0.77±0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.

KW - BpV

KW - Neuron atrophy

KW - Oligodendrocyte survival

KW - PTEN

KW - Spinal cord injury

UR - http://www.scopus.com/inward/record.url?scp=84902084784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902084784&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2014.02.039

DO - 10.1016/j.neulet.2014.02.039

M3 - Comment/debate

C2 - 24582904

AN - SCOPUS:84902084784

VL - 573

SP - 64

EP - 68

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

ER -