Characterization of cells with proliferative activity after a brain injury.

ABSTRACT

The cellular responses to a brain injury are important steps in restoring the integrity and function of the brain. Proliferating cells, such as reactive astrocytes, oligodendrocyte precursor cells and microglia remodel the injured tissue. To spatially and temporally characterize the initial cellular responses in vivo, proliferating cells were pulse-labeled with BrdU soon after (the 2nd day) a cortical cryo-injury, and their fate was investigated by double labeling with an anti-BrdU antibody and antibodies to various cellular markers. Three days after the cryo-injury, a significant proportion of BrdU-positive cells were positive for NG2-proteoglycan, suggesting that oligodendrocyte progenitors (OPCs) were induced in response to injury. One-two weeks after the cryo-injury, the number of OPC was reduced and GFAP/BrdU double-positive cells, in turn, became dominant, while cells with mature oligodendrocyte markers did not increase significantly. Neuronal markers were rarely co-localized with BrdU immunoreactivity throughout the period studied. These findings imply that OPCs are prone to differentiate to astrocytes in the lesioned site. In this cryo-injury model, treatment with thyroid hormone (T4) altered cell fate; the increase in the number of GFAP/BrdU-positive cells was significantly diminished, and there was an increased number of mature oligodendrocytes (CNPase, PLP-positive) exhibiting BrdU immunoreactivity. These findings suggest that modification of proliferating progenitors in injured brain by hormonal or chemical treatment might benefit functional regeneration.