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.
It was investigated whether MSC treatment improves recovery after neonatal stroke and whether MSC overexpressing brain-derived neurotrophic factor (MSC-BDNF) further enhances recovery.
To prove it scientists 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.
It has been shown that 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.
It can be clearly stated, that 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.
Keywords: mesenchymal stem cells, brain-derived neurotrophic factor, cerebral artery occlusion.