Acetyl-l-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery

S. P. Patel, P. G. Sullivan, T. S. Lyttle, D. S.K. Magnuson, A. G. Rabchevsky

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

We have recently documented that treatment with the alternative biofuel, acetyl- l-carnitine (ALC, 300 mg/kg), as late as 1 h after T10 contusion spinal cord injury (SCI), significantly maintained mitochondrial function 24 h after injury. Here we report that after more severe contusion SCI centered on the L1/L2 segments that are postulated to contain lamina X neurons critical for locomotion (the "central pattern generator"), ALC treatment resulted in significant improvements in acute mitochondrial bioenergetics and long-term hind limb function. Although control-injured rats were only able to achieve slight movements of hind limb joints, ALC-treated animals produced consistent weight-supported plantar steps 1 month after injury. Such landmark behavioral improvements were significantly correlated with increased tissue sparing of both gray and white matter proximal to the injury, as well as preservation of choline acetyltransferase (ChAT)-positive neurons in lamina X rostral to the injury site. These findings signify that functional improvements with ALC treatment are mediated, in part, by preserved locomotor circuitry rostral to upper lumbar contusion SCI. Based on beneficial effects of ALC on mitochondrial bioenergetics after injury, our collective evidence demonstrate that preventing mitochondrial dysfunction acutely "promotes" neuroprotection that may be associated with the milestone recovery of plantar, weight-supported stepping.

Original languageEnglish
Pages (from-to)296-307
Number of pages12
JournalNeuroscience
Volume210
DOIs
StatePublished - May 17 2012

Bibliographical note

Funding Information:
The authors are thankful for the expert technical assistance of Chris R. O'Dell and Khalid C. Eldhan. This study was supported by KSCHIRT #8–13 (A. G. R.), NIH/NINDS R01NS069633 (A. G. R. and P. G. S.), NIH/NINDS P30 NS051220 , and a generous donation from the Michael and Helen Schaffer Foundation, Boston, MA, USA.

Keywords

  • Central pattern generator
  • L1/L2 SCI
  • Locomotor function
  • Locomotor neuronal circuitry
  • Mitochondrial bioenergetics
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience (all)

Fingerprint

Dive into the research topics of 'Acetyl-l-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery'. Together they form a unique fingerprint.

Cite this