Mesenchymal stem cell transplantation attenuates brain injury after neonatal stroke.

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.

• 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)

Chemical References

• Brain-Derived Neurotrophic Factor

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)