Abstract | BACKGROUND AND PURPOSE:
Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulating repair processes. We investigated whether MSC treatment improves recovery after neonatal stroke and whether MSC overexpressing brain-derived neurotrophic factor (MSC- BDNF) further enhances recovery. METHODS: We performed 1.5-hour transient middle cerebral artery occlusion in 10-day-old rats. Three days after reperfusion, pups with evidence of injury by diffusion-weighted MRI were treated intranasally with MSC, MSC- BDNF, or vehicle. To determine the effect of MSC treatment, brain damage, sensorimotor function, and cerebral cell proliferation were analyzed. RESULTS: Intranasal delivery of MSC- and MSC- BDNF significantly reduced infarct size and gray matter loss in comparison with vehicle-treated rats without any significant difference between MSC- and MSC- BDNF-treatment. Treatment with MSC- BDNF significantly reduced white matter loss with no significant difference between MSC- and MSC- BDNF-treatment. Motor deficits were also improved by MSC treatment when compared with vehicle-treated rats. MSC- BDNF-treatment resulted in an additional significant improvement of motor deficits 14 days after middle cerebral artery occlusion, but there was no significant difference between MSC or MSC- BDNF 28 days after middle cerebral artery occlusion. Furthermore, treatment with either MSC or MSC- BDNF induced long-lasting cell proliferation in the ischemic hemisphere. CONCLUSIONS:
Intranasal administration of MSC after neonatal stroke is a promising therapy for treatment of neonatal stroke. In this experimental paradigm, MSC- and BNDF-hypersecreting MSC are equally effective in reducing ischemic brain damage.
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Authors | Cindy T J van Velthoven, R Ann Sheldon, Annemieke Kavelaars, Nikita Derugin, Zinaida S Vexler, Hanneke L D M Willemen, Mirjam Maas, Cobi J Heijnen, Donna M Ferriero |
Journal | Stroke
(Stroke)
Vol. 44
Issue 5
Pg. 1426-32
(May 2013)
ISSN: 1524-4628 [Electronic] United States |
PMID | 23539530
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Brain-Derived Neurotrophic Factor
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Topics |
- Animals
- Brain
(pathology)
- Brain-Derived Neurotrophic Factor
(therapeutic use)
- Cell Proliferation
- Disease Models, Animal
- Infarction, Middle Cerebral Artery
(drug therapy, pathology, therapy)
- Mesenchymal Stem Cell Transplantation
(methods)
- Nerve Fibers, Myelinated
(pathology)
- Neurons
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Stroke
(pathology, therapy)
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