TY - JOUR
T1 - Effects of Mitochondrial Transplantation on Bioenergetics, Cellular Incorporation, and Functional Recovery after Spinal Cord Injury
AU - Gollihue, Jenna L.
AU - Patel, Samir P.
AU - Eldahan, Khalid C.
AU - Cox, David H.
AU - Donahue, Renee R.
AU - Taylor, Bradley K.
AU - Sullivan, Patrick G.
AU - Rabchevsky, Alexander G.
N1 - Publisher Copyright:
© 2018, Mary Ann Liebert, Inc.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Basso
KW - Beattie
KW - Bresnahan locomotor rating scale
KW - Von Frey hair test
KW - mitochondrial respiration
KW - transgenic labeling
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U2 - 10.1089/neu.2017.5605
DO - 10.1089/neu.2017.5605
M3 - Article
C2 - 29648982
AN - SCOPUS:85049666825
SN - 0897-7151
VL - 35
SP - 1800
EP - 1818
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 15
ER -