Microglia transplantation attenuates white matter injury in rat chronic ischemia model via matrix metalloproteinase-2 inhibition
| Autor: | Kiryo Wakabayashi, Yuri Shiota, Tatsuzo Watanabe, Dashdemberel Narantuya, Abdullah Md. Sheikh, Shuhei Yamaguchi, Atsushi Nagai, Shotai Kobayashi, Seung U. Kim, Junichi Masuda |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Carotid Artery Diseases
Male Pathology medicine.medical_specialty Ischemia Matrix Metalloproteinase Inhibitors Mesenchymal Stem Cell Transplantation Nerve Fibers Myelinated Severity of Illness Index Brain Ischemia Cell Line White matter Brain ischemia Random Allocation Cell Movement medicine Animals Humans RNA Messenger Rats Wistar Molecular Biology Microglia business.industry General Neuroscience Mesenchymal stem cell Brain Mesenchymal Stem Cells medicine.disease Rats Transplantation Disease Models Animal medicine.anatomical_structure Astrocytes Chronic Disease Neuroglia Matrix Metalloproteinase 2 Neurology (clinical) Stem cell business Developmental Biology |
| Zdroj: | Brain research. 1316 |
| ISSN: | 1872-6240 |
| Popis: | Chronic cerebral ischemia is thought to induce white matter lesions (WMLs), which contribute to subcortical vascular dementia. Although glial activation and protease upregulation are believed to modify WML pathology, effective therapy remains elusive. Here, we compare the efficacy of microglial cell transplantation and mesenchymal stem cell (MSC) transplantation in protecting against WML development in a chronic cerebral hypoperfusion rat model. A microglial cell line (HMO6), MSC cell line (B10) or vehicle (phosphate-buffered saline; PBS) was intravenously injected, and the appearance and severity of WMLs were evaluated. Transplanted HMO6 and B10 cells migrated to sites of WMLs, including the corpus callosum (CC) and caudoputamen (CP), reduced the severity of WMLs, and inhibited the accumulation and activation of microglia and astrocytes. Transplantation of both cell types reduced the level of matrix metalloproteinase (MMP)-2 mRNA in microglia of the CC. MMP-2 protein level and activity were also both greatly reduced in the same region. Our results indicate that transplantation of either microglial cells or mesenchymal stem cells could inhibit chronic cerebral ischemia-induced WML formation by decreasing MMP-2 expression in microglia and decreasing MMP-2 activity in the CC region. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect