Microglia transplantation attenuates white matter injury in rat chronic ischemia model via matrix metalloproteinase-2 inhibition.
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.
Narantuya
Dashdemberel
D
Department of Neurology, Shimane University School of Medicine, Izumo, Japan.
Nagai
Atsushi
A
Sheikh
Abdullah Md
AM
Wakabayashi
Kiryo
K
Shiota
Yuri
Y
Watanabe
Tatsuzo
T
Masuda
Junichi
J
Kobayashi
Shotai
S
Kim
Seung U
SU
Yamaguchi
Shuhei
S
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002460:Cell Line; D002465:Cell Movement; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D017628:Microglia / Q000502:physiology / Q000637:transplantation*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat