This study was designed to follow the effects of bone marrow stromal cell (BMSC) administration in rats after traumatic brain injury (TBI) for a 3-month period.
Forty adult female Wistar rats were injured by a controlled cortical impact and, 1 week later, were injected intravenously with one of three different doses of BMSCs (2 × 106, 4 × 106, or 8 × 106 cells per animal) obtained in male rats. Control rats received phosphate-buffered saline (PBS). Neurological function in these rats was studied using a neurological severity scale (NSS). The rats were killed 3 months after injury, and immunohistochemical stains were applied to brain samples to study the distribution of the BMSCs. Additional brain samples were analyzed by quantitative enzyme-linked immunosorbent assays to measure the expression of the growth factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).
Three months after injury, BMSCs were present in the injured brain and their number was significantly greater in animals that received 4 × 106 or 8 × 106 BMSCs than in animals that received 2 × 106 BMSCs. The cells were primarily distributed around the lesion boundary zone. Functional outcome was significantly better in rats that received 4 × 106 or 8 × 106 BMSCs, compared with control animals, although no improvement was seen in animals that received 2 × 106 BMSCs. All doses of BMSCs significantly increased the expression of BDNF but not that of NGF; however, this increase was significantly larger in animals that received 4 × 106 or 8 × 106 BMSCs than in controls or animals that received 2 × 106 BMSCs.
In summary, when injected in rats after TBI, BMSCs are present in the brain 3 months later and significantly improve functional outcome.