Cell and Organ Transplantology. 2025; 13(1):54-61 (e2025131177).
DOI: 10.22494/cot.v13i1.177
Granulocyte colony-stimulating factor modulates glial scar formation after hemorrhagic stroke in rats by mobilizing mesenchymal cells
Grabovoy A.
, Mervinsky T., Savosko S., Kondaurova H., Konovalova L., Yaremenko L.
- Bogomolets National Medical University, Kyiv, Ukraine
Abstract
A glial scar typically develops in the brain following a stroke and represents a common astrocytic response to injury. While astrocytes are the primary cell type involved in this process, non-glial cells also contribute to scar formation. The immunophenotype of these additional cell populations remains poorly characterized. Identifying these cells could deepen our understanding of glial scar development and help uncover potential therapeutic targets.
Aim. To identify cells of potential mesenchymal origin in the glial scar following hemorrhagic stroke (HS) and assess changes in their number under the influence of granulocyte colony-stimulating factor (G-CSF) and its combination with dexamethasone (DEX).
Materials and methods: A unilateral model of hemorrhagic stroke was induced in 120 rats, which were divided into three groups: HS, HS+G-CSF, and HS+G-CSF+DEX. The control group consisted of sham-operated animals without stroke induction. On days 1, 3, 10, 30, and 60 post-injury, glial scar formation was assessed by immunohistochemistry. Brain sections were analyzed for GFAP expression and the presence of CD44⁺, CD68⁺, and CD90⁺ cells. Densitometric analysis of the GFAP-positive area was performed.
Results. G-CSF increased the number of CD44⁺ cells in the glial scar area during the acute phase after stroke. The combination of G-CSF and DEX attenuated the accumulation of CD44⁺ cells but promoted their prolonged presence. G-CSF also enhanced the mobilization of CD68⁺ cells to the site of hemorrhage, while DEX delayed their appearance, possibly due to its anti-inflammatory effects during the acute phase. CD68⁺ cells in the lesion area may represent not only phagocytes but also mesenchymal progenitor cells. The mobilization of CD90⁺ cells to the glial scar formation zone is limited and infrequent but increases under the influence of G-CSF. Nevertheless, their presence indicates the involvement of mesenchymal stem cells in regenerative processes following hemorrhagic stroke, as these cell types are not detected in the intact brain. Additionally, G-CSF reduced the intensity of astroglial activation following injury.
Conclusions. Cells of mesenchymal origin contribute to glial scar formation after hemorrhagic stroke, while such involvement is absent in the sham-operated group, aside from the rare appearance of CD44⁺ cells. G-CSF modulates glial scar development by promoting the accumulation of mesenchymal cells in the injury area, which contributes to greater compactness of the scar without increasing its connective tissue component. G-CSF even reduces astrogliosis, a process that is otherwise exacerbated by dexamethasone during glial scar formation after brain hemorrhage.
Key words: cerebral stroke; glial scar; mesenchymal stem cell; granulocyte colony-stimulating factor; CD44; CD68
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Grabovoy A, Mervinsky T, Savosko S, Kondaurova H, Konovalova L, Yaremenko L. Granulocyte colony-stimulating factor modulates glial scar formation after hemorrhagic stroke in rats by mobilizing mesenchymal cells . Cell Organ Transpl. 2025; 13(1):54-61 (e2025131177). doi: https://doi.org/10.22494/cot.v13i1.177
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