Effects of Mitochondrial Transplantation on Bioenergetics, Cellular Incorporation, and Functional Recovery after Spinal Cord Injury

Jenna L. Gollihue, Samir P. Patel, Khalid C. Eldahan, David H. Cox, Renee R. Donahue, Bradley K. Taylor, Patrick G. Sullivan, Alexander G. Rabchevsky

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Our previous studies reported that pharmacological maintenance of mitochondrial bioenergetics after experimental spinal cord injury (SCI) provided functional neuroprotection. Recent evidence indicates that endogenous mitochondrial transfer is neuroprotective as well, and, therefore, we extended these studies with a novel approach to transplanting exogenous mitochondria into the injured rat spinal cord. Using a rat model of L1/L2 contusion SCI, we herein report that transplantation of exogenous mitochondria derived from either cell culture or syngeneic leg muscle maintained acute bioenergetics of the injured spinal cord in a concentration-dependent manner. Moreover, transplanting transgenically labeled turbo green fluorescent (tGFP) PC12-derived mitochondria allowed for visualization of their incorporation in both a time-dependent and cell-specific manner at 24 h, 48 h, and 7 days post-injection. tGFP mitochondria co-localized with multiple resident cell types, although they were absent in neurons. Despite their contribution to the maintenance of normal bioenergetics, mitochondrial transplantation did not yield long-term functional neuroprotection as assessed by overall tissue sparing or recovery of motor and sensory functions. These experiments are the first to investigate mitochondrial transplantation as a therapeutic approach to treating spinal cord injury. Our initial bioenergetic results are encouraging, and although they did not translate into improved long-term outcome measures, caveats and technical hurdles are discussed that can be addressed in future studies to potentially increase long-term efficacy of transplantation strategies.

Original languageEnglish
Pages (from-to)1800-1818
Number of pages19
JournalJournal of Neurotrauma
Volume35
Issue number15
DOIs
StatePublished - Aug 1 2018

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health (NIH) F31 NS093904-01A1 (J.L.G.), Conquer Paralysis Now (A.G.R.), NIH R21 NS096670 (A.G.R.), Spinal Cord and Brain Injury Research Center (SCoBIRC) Chair Endowment (A.G.R.), and NIH/National Institute of Neurological Disorders and Stroke (NINDS) 2P30NS051220.

Funding Information:
This study was supported by National Institutes of Health (NIH) F31 NS093904-01A1 ( J.L.G.), Conquer Paralysis Now (A.G.R.), NIH R21 NS096670 (A.G.R.), Spinal Cord and Brain Injury Research Center (SCoBIRC) Chair Endowment (A.G.R.), and NIH/ National Institute of Neurological Disorders and Stroke (NINDS) 2P30NS051220.

Publisher Copyright:
© 2018, Mary Ann Liebert, Inc.

Keywords

  • Basso
  • Beattie
  • Bresnahan locomotor rating scale
  • Von Frey hair test
  • mitochondrial respiration
  • transgenic labeling

ASJC Scopus subject areas

  • Clinical Neurology

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