title: Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.
abstract: We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day of MWM trials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation.
authors.affiliation: Departments of Pediatric Surgery and.
authors.forename: Supinder S
authors.initials: SS
authors.lastname: Bedi
authors.forename: Robert
authors.initials: R
authors.lastname: Hetz
authors.forename: Chelsea
authors.initials: C
authors.lastname: Thomas
authors.forename: Philippa
authors.initials: P
authors.lastname: Smith
authors.forename: Alex B
authors.initials: AB
authors.lastname: Olsen
authors.forename: Stephen
authors.initials: S
authors.lastname: Williams
authors.forename: Hasen
authors.initials: H
authors.lastname: Xue
authors.forename: Kevin
authors.initials: K
authors.lastname: Aroom
authors.forename: Karen
authors.initials: K
authors.lastname: Uray
authors.forename: Jason
authors.initials: J
authors.lastname: Hamilton
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mays
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
mesh_terms: D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D007275:Injections, Intravenous; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009043:Motor Activity; D039902:Multipotent Stem Cells / Q000637:transplantation*; D051381:Rats; D011930:Reaction Time; D020127:Recovery of Function; D013037:Spatial Behavior; D013997:Time Factors
keywords: Adult stem cells; Neuroimmune; Rat model; Stem/progenitor cell