Injection Time-Dependent Effect of Adult Human Bone Marrow Stromal Cell Transplantation in a Rat Model of Severe Traumatic Brain Injury
Eun Young Han, Min Ho Chun, Sang Tae Kim and Dong-pyo Lim
Affiliation: Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa Gu, Seoul, South Korea.
The object of this study is to evaluate the effects of injecting adult human bone marrow stromal cells
(hBMSCs) into rats with severe traumatic brain injury in acute phase and to determine more optimal injection timing between
day 1 and day 2 postinjury. The lateral fluid percussion injury model was used. Adult hBMSCs were transplanted
into hemisphere to injury sites in the corpus callosum ipsilateral on day 1 (n = 12) or day 7 (n = 8) after injury. A control
group (n = 7) underwent only a sham operation without stem cell transplantation. Rats in all groups were analyzed by
magnetic resonance spectroscopy (MRS), and by using behavioral, rotarod, and Barnes maze tests on day 1, 7, 14, and 42.
Another nine randomly designated rats were sacrificed for immunohistochemical staining. Behavioral test scores increased
significantly at all time-points after TBI in the day 7-injected group, compared to the others (p=0.008). GFAP
staining was lower on day 42 in day 7-injected rats than in those injected on day 1. But no significant inter- or intra-group
differences were observed for other tests. The injection of hBMSCs was found to have limited therapeutic potential with
respect to neuroprotection after traumatic brain injury. However, because injection on day 7 after TBI produced greater
functional improvements in neurobehavioral tests and more effectively suppressed astroglial activation than an injection
on post-injury day 1, we cautiously recommend the injection time of day 7 post injury in hBMSCs transplantation in severe
TBI, rather than day 1 post injury but further studies on developing hBMSC-based new therapeutic approaches
should be warranted for improving neuroprotection in severe TBI.
Keywords: Human bone marrow stromal cells, injection timing, traumatic brain injuryinjection timing, fluid percussion injury, Magnetic Resonance Spectroscopy, Immunohistochemical Analyses, Immunohistochemical Staining of Brain Tissue, Neurobehavioral Examination
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