| RRC ID |
55778
|
| 著者 |
Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Oka S, Suzuki J, Sasaki Y, Nagahama H, Hashi K, Kocsis JD, Honmou O.
|
| タイトル |
Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model.
|
| ジャーナル |
Neuroscience
|
| Abstract |
Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Moreover, deterioration of amyloid-β (Aβ) clearance due to the failure of the transvascular BBB transport system results in accumulation of Aβ in the brain. Intravenous infusion of mesenchymal stem cells (MSCs) elicits functional recovery in experimental models including stroke and spinal cord injury. One effect of MSCs is to restore disrupted BBB through remodeling of microvasculature. Using spontaneously hypertensive rats (stroke-prone) with impaired cognitive function as a CSVD model, we have shown that infused MSCs has a therapeutic effect for cognitive function. Restoration of BBB function via remodeling of microvasculature and inhibition of Aβ accumulation could inhibit progressive brain atrophy and lead to restore cognitive dysfunction. Gene expression analysis indicated that infused MSCs activates both transforming growth factor-β and angiopoietin 1 signaling pathways and promotes the remodeling of microvasculature. Thus, infused MSCs may represent a novel therapy for both VD and AD.
|
| 巻・号 |
408
|
| ページ |
361-377
|
| 公開日 |
2019-6-1
|
| DOI |
10.1016/j.neuroscience.2019.04.018
|
| PII |
S0306-4522(19)30258-1
|
| PMID |
30999031
|
| MeSH |
Animals
Behavior, Animal / physiology
Blood-Brain Barrier / pathology
Cerebral Small Vessel Diseases / complications*
Cerebral Small Vessel Diseases / pathology
Cognition / physiology*
Cognitive Dysfunction / etiology
Cognitive Dysfunction / pathology
Cognitive Dysfunction / therapy*
Disease Models, Animal
Infusions, Intravenous
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells
Rats
Rats, Inbred SHR
Recognition, Psychology / physiology*
|
| IF |
3.244
|
| 引用数 |
4
|
| リソース情報 |
| ラット |
W-Tg(CAG-GFP)184Ys (strainID=525) |
