Abstract | OBJECTIVE: METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. RESULTS: Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05). CONCLUSIONS:
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Authors | Atsuhiko Toyoshima, Takao Yasuhara, Masahiro Kameda, Jun Morimoto, Hayato Takeuchi, Feifei Wang, Tatsuya Sasaki, Susumu Sasada, Aiko Shinko, Takaaki Wakamori, Mihoko Okazaki, Akihiko Kondo, Takashi Agari, Cesario V Borlongan, Isao Date |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 6
Pg. e0127302
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26075717
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chemokines
- Nerve Growth Factors
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Topics |
- Animals
- Behavior, Animal
- Brain Infarction
(etiology, pathology, physiopathology)
- Cell Movement
- Cell Tracking
- Chemokines
(metabolism)
- Disease Models, Animal
- Ischemic Attack, Transient
(pathology, physiopathology, therapy)
- Male
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells
(metabolism)
- Nerve Growth Factors
(metabolism)
- Rats
- Time Factors
- Treatment Outcome
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