Bone-Marrow-Derived Endothelial Progenitor Cell Treatment in a Model of Lateral Fluid Percussion Injury in Rats: Evaluation of Acute and Subacute Outcome Measures.
Traumatic brain injury (TBI) continues to be a serious health care issue while therapies to treat TBI remain elusive. Promising results from the use of endothelial progenitor cells (EPCs) in numerous disease states highlight the pleiotropic capacity of this cell type. We have previously demonstrated that EPC-conditioned media reduces axonal degeneration subsequent to in vitro oxygen-glucose deprivation insult and concurrently improves white matter and microvascular outcome in vivo after mid-line fluid percussion injury. In the current study, we evaluated the effectiveness of allogeneic endothelial cells derived from rat bone marrow on microvascular recovery and neuronal sparing after lateral fluid percussion injury. We observed reduced expression of activated caspase-3 and poly (ADP-ribose) polymerase cleavage at 72 h post-injury. Subacute injury assessments at 30 days post-injury using immunohistochemistry indicated nonsignificant effects on microvascular outcome and neuronal cell density in the hippocampus. Behavioral testing using the Morris Water Maze and rotarod demonstrated significant improvement in locomotor function, as measured by the rotarod task, but no significant differences in spatial memory ability. The data suggest that EPCs contribute to improvements in the early phase of secondary injury through inhibition of apoptosis whereas the effects on longer-term recovery were less clearly defined. There is potential in the use of EPCs to treat secondary injury post-TBI; however, optimization of their effects through increased duration or homing capacities remains to be examined.
1 Keenan Research Center in the Li Ka Shing Knowledge Institute at St. Michael's Hospital , Toronto, Ontario, Canada .
Eugene
E
Park
1 Keenan Research Center in the Li Ka Shing Knowledge Institute at St. Michael's Hospital , Toronto, Ontario, Canada .
Katya
K
Park
1 Keenan Research Center in the Li Ka Shing Knowledge Institute at St. Michael's Hospital , Toronto, Ontario, Canada .
Elaine
E
Liu
2 Department of Neurosurgery, Tianjin Medical University , Tianjin Neurological Institute, Tianjin, China .
Rongcai
R
Jiang
2 Department of Neurosurgery, Tianjin Medical University , Tianjin Neurological Institute, Tianjin, China .
Jianning
J
Zhang
1 Keenan Research Center in the Li Ka Shing Knowledge Institute at St. Michael's Hospital , Toronto, Ontario, Canada .|3 Institute of Medical Sciences, University of Toronto , Toronto, Ontario, Canada .|4 Departments of Anesthesia & Surgery, University of Toronto , Toronto, Ontario, Canada .
Andrew J
AJ
Baker
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D000070642:Brain Injuries, Traumatic; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000637:transplantation*; D008297:Male; D018782:Maze Learning; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000379:methods
apoptosis; cell therapy; endothelial progenitor cells; fluid percussion injury; neuroprotection; traumatic brain injury