|
|||||
|
|
The protective effect of bone marrow mesenchymal stem cells in a rat model of ischemic stroke via reducing the C-Jun N-terminal kinase expression |
|
| Authors: | Zeinab Vahidinia Abolfazl Azami Tameh Majid Nejati Cordian Beyer Sayyed Alireza Talaei Sepideh Etehadi Moghadam Mohammad Ali Atlasi |
| Affiliation: | 1. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran;2. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;3. Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany;4. Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran |
| Abstract: | Ischemic stroke is the main cause of disability and mortality worldwide. Apoptosis and inflammation have an important role in ischemic brain injury. Mesenchymal stem cells (MSCs) have protective effects on stroke treatment due to anti-inflammatory properties. The inhibition of the C-Jun N-terminal kinase (JNK) pathway may be one of the molecular mechanisms of the neuroprotective effect of MSCs in ischemic brain injury.Twenty-eight male Wistar rats were divided randomly into 3 groups. Except the sham group, others subjected to transient middle cerebral artery occlusion (tMCAO). Bone marrow MSCs or saline were injected 3 h after tMCAO. Sensorimotor behavioral tests were performed 24 and 72 h after ischemia and reperfusion (I/R). The rats were sacrificed 72 h after I/R and infarct volume was measured by TTC staining. The number of apoptotic neurons and astrocytes in the peri-infarct area was assessed by TUNEL assay. The morphology of cells was checked by Nissl staining, and the expression of p-JNK was detected by immunohistochemistry and Western blot.Behavioral scores were improved and infarct volume was reduced by MSCs 24 h and 72 h after tMCAO. TUNEL assay showed that neuronal apoptosis and astroglial activity in the penumbra region were reduced by MSCs. Also, Nissl staining showed lower neuronal apoptosis in BMSCs-treated rats compared to controls. JNK phosphorylation which was profoundly induced by ischemia was significantly decreased after MSCs treatment.We concluded that anti-apoptotic and anti-inflammatory effects of MSCs therapy after brain ischemia may be associated with the down-regulation of p-JNK. |
| Keywords: | Corresponding authors at: Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran. AP-1 Activator protein 1 Apaf-1 Apoptotic protease activating factor 1 ATF Activating transcription factor BDNF Brain-derived neurotrophic factor BMSCs Bone marrow mesenchymal stem cells BSA Bovine serum albumin CBF Cerebral blood flow CCA Common carotid artery CNS Central nervous system DAB Diaminobenzidine DMEM Dulbecco's modified Eagle's medium ERK Extracellular signal-regulated kinase FBS Fetal bovine serum FITC Fluorescein isothiocyanate GFAP Glial fibrillary acidic protein HRP Horseradish peroxidase ICA Internal carotid artery IHC Immunohistochemistry JNK C-Jun N-terminal kinase MAPK Mitogen-activated protein kinase MCAO Middle cerebral artery occlusion NBF Neutral-buffered Formalin PBS Phosphate-buffered saline PE Phycoerythrin PI3K/Akt Phosphatidylinositol-3-kinase/ protein kinase B, Transducer and activator of transcription 1 TNF-α Tumor necrosis factors alpha TPA Tissue plasminogen activator TTC Triphenyltetrazolium chloride TUNEL Terminal deoxynucleotidyl-transferase -mediated dUTP-biotin nick-end labeling Mesenchymal stem cells Stroke C-Jun N-terminal kinase Therapy |
| 本文献已被 ScienceDirect 等数据库收录！ | |