Zhangrong Li1, Huiling Ye2, Xueli Cai3, Weiwen Sun4, Bin He4, Zhihua Yang5, Pingyi Xu6. 1. Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 2. Geriatric Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 3. Department of Neurology, The Fifth Affiliated Hospital of Wenzhou Medical College, Guangzhou 323000, China. 4. Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. 5. Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. Electronic address: xiaoyangzhihua@126.com. 6. Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. Electronic address: pingyixu@sina.com.
Abstract
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.
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.