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.
journal_name
Strokejournal_title
Strokeauthors
van Velthoven CT,Sheldon RA,Kavelaars A,Derugin N,Vexler ZS,Willemen HL,Maas M,Heijnen CJ,Ferriero DMdoi
10.1161/STROKEAHA.111.000326subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1426-32issue
5eissn
0039-2499issn
1524-4628pii
STROKEAHA.111.000326journal_volume
44pub_type
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