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Updated: Jan 6, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Bone marrow-mesenchymal stem cells modulate microglial activation in the peri-infarct area in rats during the acute
Zhangrong Li1, Huiling Ye2, Xueli Cai3
1Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Aim:
Bone marrow-mesenchymal stem cells (BM-MSCs) possess immunomodulatory properties in the brain. However, it remains unclear whether intravenously transplanted BM-MSCs have a neuromodulator effect on the activation of microglias after ischemic stroke. This study aimed to investigate the immunomodulatory effect of BM-MSCs on the regulation of brain microglial inactivation during the acute phase of stroke.
Methods:
A rat model of middle cerebral artery occlusion (MCAO) was established. Rat BM-MSCs were transplanted through the tail vein at 12 h after MCAO. CD200 Receptor 1 (CD200R1) antibody was injected into the peri-infarct area of the rat brain at 3 h prior to BM- MSCs transplantation. Protein expression was determined by immunofluorescence staining and Western blot. The volume of the infarct area was determined by TTC (2,3,5-triphenyltetrazolium hydrochloride) staining. Neuron apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.
Results:
In vitro study showed that co-culture with BM-MSCs significantly decreased LPS-induced iNOS expression in the microglial cells. Immunofluorescence and Western blot consistently revealed that BM-MSC transplantation significantly reduced the IBA-expressing microglial cells and IBA protein levels in the peri-infarct area. The inhibitory effect of BM-MSC on IBA expression was significantly attenuated by pretreatment of CD200R1 neutralizing antibody in the peri-infarct zone. BM-MSC transplantation significantly reduced the infarct volume, protected neuron apoptosis, and increased neuronal CD200 expression in the peri-infarct area.
Conclusion:
The transplanted BM-MSCs exerted immunomodulatory effect by inactivating the microglias in the peri-infarct area, at least partially, via the CD200-CD200R1 signaling.
Insights
Intravenously transplanted bone marrow-mesenchymal stem cells (BM-MSCs) reduce microglial activation after ischemic stroke. This effect is mediated by the CD200-CD200R1 signaling pathway, decreasing infarct volume and neuron apoptosis.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Bone marrow-mesenchymal stem cells (BM-MSCs) have known immunomodulatory effects.
- The impact of intravenously administered BM-MSCs on microglial activation post-ischemic stroke is not well understood.
Purpose of the Study:
- To investigate the immunomodulatory effect of BM-MSCs on microglial inactivation in the acute phase of ischemic stroke.
- To explore the role of the CD200-CD200R1 signaling pathway in this process.
Main Methods:
- Established a rat model of middle cerebral artery occlusion (MCAO).
- Administered BM-MSCs intravenously 12 hours post-MCAO.
- Utilized CD200 Receptor 1 (CD200R1) antibody to block signaling.
- Assessed protein expression via immunofluorescence and Western blot.
- Quantified infarct volume and neuron apoptosis using TTC and TUNEL staining, respectively.
Main Results:
- BM-MSC co-culture reduced LPS-induced iNOS expression in microglial cells in vitro.
- BM-MSC transplantation decreased microglial activation (IBA-expressing cells and protein levels) in the peri-infarct area.
- Blocking CD200R1 attenuated the inhibitory effect of BM-MSCs on microglial activation.
- BM-MSC treatment reduced infarct volume, protected against neuron apoptosis, and increased neuronal CD200 expression.
Conclusions:
- Transplanted BM-MSCs exert an immunomodulatory effect by inactivating microglias in the peri-infarct area after ischemic stroke.
- This microglial inactivation is, at least partially, mediated through the CD200-CD200R1 signaling pathway.
