Granulocyte colony-stimulating factor induces the migration of non-resident cells to intracerebral hemorrhage

Abstract

The aim of the study is to determine the effect of granulocyte colony-stimulating factor (rHuG-CSF) on the migration of non-resident cells into the region of intracerebral hemorrhage (ICH), which can potentially be considered as mesenchymal stem cells. Materials and methods. In the experiment, unilateral ICH was simulated in rats by injection of autologous blood into the right hemisphere. Immunohistochemical method was used to study perihematomal area on day 1, 3, 10, 30, and 60 after ICH modeling. The appearance of cells expressing CD44, CD68, and CD146 markers was evaluated on a 3-point scale after penetrating trauma (PT) of the brain, ICH, and ICH with the growth factor injection (ICH/rHuG-CSF). Results. In contrast to PT, ICH intensified the infiltration of CD44+ cells in the perihematomal area of the brain and caused the appearance of CD68+ and CD146+ cells in hemorrhage. The specific density of CD44+ cells was decreased on day 60 after ICH, and the effect of rHuG-CSF consisted in reducing the density of CD44+ cells on days 30 and 60. The appearance of CD68+ and CD146+ cells in the perihematomal area was seen after 10 days and further their detection was rare, while after the rHuG-CSF injection, the infiltration by cells with a similar immunophenotype was detected on day 3 ICH with a tendency to accumulate. Conclusions. Infiltration by cells expressing CD44, CD68, and CD146 into the perihematomal area of the rat brain was heterogeneous as to the time after brain injury. The appearance of cells with specified immunophenotype could be associated with hematoma elimination, angiogenesis processes, and other mechanisms of the perihematomal brain region remodeling, in which mesenchymal stem cells were involved. rHuG-CSF modulated the migration of CD68+ and CD146+ cells, which consisted in their earlier and more intense migration to the damaged area of the brain after ICH.