Implications of p53 protein expression in experimental spinal cord injury.

In order to clarify the role of p53, known as a tumor suppressor protein and also as a key molecule of apoptotic cell death, we have studied p53 expression in relation to localization, time course, cell type, and TUNEL reaction in a rat model of transectional spinal cord injury. Other apoptosis related molecules, p21, Bcl-2 and Bax, that are in the cascade of p53 pathway, were also examined. p53 was expressed in cells residing in the vicinity of transection as early as 30 min. For the next 2 days, the positive cells spread in distribution, increased in number, and thereafter decreased. p53 immunoreactivity was localized primarily to the nucleus but not to cytoplasm. Double-staining with glial cell markers revealed that p53 immunoreactivity was often co-localized in microglia, oligodendrocytes and astrocytes, but not in neurons. In view of the results of the double-staining of p53 and Bcl-2, Bax or TUNEL, a variety of apoptosis-related molecules are expressed with p53, all within the first three days of injury. Further, the process of apoptosis via the p53, pathway appears complex even in this simple model of CNS injury. Our study suggests that the manipulation of these apoptosis-related molecules may prove useful in modifying the cell and tissue damage in traumatic CNS injury.