Transplanted bone marrow stromal cells improves cognitive dysfunction due to diffuse axonal injury in rats.

Diffuse axonal injury (DAI) often leads to persistent cognitive dysfunction in spite of the lack of gross lesions on MRI. Therefore, this study was aimed to evaluate whether transplanted bone marrow stromal cells (BMSC) can improve DAI-induced cognitive dysfunction or not. The rats were subjected to impact acceleration head injury, using a pneumatic high-velocity impactor. The BMSC were harvested from the mice and were cultured. The BMSC (4.0 x 10(5) cells) or vehicle were stereotactically transplanted into the right striatum at 10 days post-injury. Cognitive function analysis was repeated at 1, 2, and 4 weeks post-injury, using the Morris water maze test. Histological analysis was performed at 2, 8 and 20 weeks post-injury, using double fluorescence immunohistochemistry. Transplanted BMSC were widely distributed in the injured brain and gradually acquired the phenotypes of neurons and astrocytes over 20 weeks. In addition, they significantly improved DAI-induced cognitive dysfunction as early as 2 weeks post-injury, although their processes of neuronal differentiation were not completed at this time point. The findings suggest that the engrafted BMSC may exhibit this early beneficial effect on cognitive function by producing neuroprotective or neurotrophic factors. In conclusion, direct transplantation of BMSC may serve as a novel therapeutic strategy to enhance the recovery from DAI-induced cognitive impairment.