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 ± 2.7 mm(-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.

• Authors: Chandler L Walker, Xiao-Ming Xu
• Journal: Neuroscience letters (Neurosci Lett) Vol. 573 Pg. 64-8 (Jun 24 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24582904 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Vanadium Compounds
• bisperoxovanadium
• PTEN Phosphohydrolase

Topics

• Animals
• Cell Survival
• Cervical Cord (drug effects, pathology)
• Female
• Motor Neurons (drug effects, pathology)
• Myelin Sheath (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oligodendroglia (drug effects, pathology)
• PTEN Phosphohydrolase (antagonists & inhibitors)
• Rats, Sprague-Dawley
• Spinal Cord Injuries (drug therapy, metabolism, pathology)
• Vanadium Compounds (pharmacology, therapeutic use)
• White Matter (drug effects, pathology)