STUDY DESIGN.: An in vivo study to examine the differentiation of endogenous neural progenitor cells in an adult rat model of post-traumatic syringomyelia. OBJECTIVE.: To quantitatively evaluate the phenotypic fate of endogenous neural progenitor cells in post-traumatic syringomyelia. SUMMARY OF BACKGROUND DATA.: Although neural progenitors have been identified in the central nervous system, their differentiation in experimental post-traumatic syringomyelia and possible role in the pathophysiology of this condition have not been investigated. METHODS.: Bromodeoxyuridine was used to label proliferating cells in a time-dependent rat model of post-traumatic syringomyelia. Eight neural markers were quantitatively analyzed to phenotype the cellular fate of these cells by double labeling immunohistochemistry. RESULTS.: Following syrinx induction, cell proliferation rate increased to 25-115 times that of cells in the intact and sham-operated controls with a peak at day 14 post-injury. In the earliest time points post-syrinx induction, ED1-expressing inflammatory cells formed a significant proportion of the proliferating population. Proliferating neural progenitor cells predominantly differentiated into NG2-expressing immature oligodendrocytes at all stages post-syrinx induction, except the final time point of 56 days. At this time, there was a peak in the number of newly generated astrocytes identified to have developed from labeled proliferating precursor cells. CONCLUSIONS.: Endogenous neural progenitors proliferate markedly following induction of post-traumatic syringomyelia which consists of two stages, initial cyst formation and progressive cyst enlargement. During the former stage, macrophages proliferate in situ and contribute to the inflammatory process. The predominant cell type formed from progeny of the induced neural progenitors was characterized to be immature oliggodendrocytes. However, during the latter stage of cyst development, there was an increase in astrocytic progeny which may represent an environment more conductive to glial scar formation acting to limit further cyst enlargement.