Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury

Chandler Walker, Melissa J. Walker, Naikui Liu, Emelie C. Risberg, Xiang Gao, Jinhui Chen, Xiao-Ming Xu

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal cord injury, and sheds light on the signaling involved in its action.

Original languageEnglish
Article numbere30012
JournalPLoS One
Volume7
Issue number1
DOIs
StatePublished - Jan 10 2012

Fingerprint

autophagy
Autophagy
Spinal Cord Injuries
spinal cord
forelimbs
Recovery
Forelimb
Wounds and Injuries
vanadium
neuroprotective effect
cell communication
novel foods
Rats
Potassium Compounds
disease models
rats
histochemistry
fluorescent antibody technique
Cell signaling
central nervous system

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. / Walker, Chandler; Walker, Melissa J.; Liu, Naikui; Risberg, Emelie C.; Gao, Xiang; Chen, Jinhui; Xu, Xiao-Ming.

In: PLoS One, Vol. 7, No. 1, e30012, 10.01.2012.

Research output: Contribution to journalArticle

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