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

• Published in: Neuroscience letters 2014-06, Vol.573, p.64-68
• Main Authors: Walker, Chandler L., Xu, Xiao-Ming
• Format: Article
• Language: English
• Subjects: Animals; bpV; Cell Survival; Cervical Cord - drug effects; Cervical Cord - pathology; Female; Motor Neurons - drug effects; Motor Neurons - pathology; Myelin Sheath - metabolism; Neuron atrophy; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oligodendrocyte survival; Oligodendroglia - drug effects; Oligodendroglia - pathology; PTEN; PTEN Phosphohydrolase - antagonists & inhibitors; Rats, Sprague-Dawley; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal cord injury; Vanadium Compounds - pharmacology; Vanadium Compounds - therapeutic use; White Matter - drug effects; White Matter - pathology
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.02.039

•Rats treated with PTEN inhibitor bisperoxovanadium for cervical spinal cord injury.•White matter, myelin, and ventrolateral funiculus oligodendrocytes were spared.•Injury-induced neuronal soma atrophy was reversed by bisperoxovanadium. 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