Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke

• Published in: Stroke (1970) Vol. 44; no. 5; pp. 1426 - 1432
• Main Authors: VELTHOVEN, Cindy T. J. Van, SHELDON, R. Ann, KAVELAARS, Annemieke, DERUGIN, Nikita, VEXLER, Zinaida S, WILLEMEN, Hanneke L. D. M, MAAS, Mirjam, HEIJNEN, Cobi J, FERRIERO, Donna M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.2013
• Subjects: Animals; Biological and medical sciences; Brain - pathology; Brain-Derived Neurotrophic Factor - therapeutic use; Cell Proliferation; Disease Models, Animal; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - therapy; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Nerve Fibers, Myelinated - pathology; Nervous system (semeiology, syndromes); Neurology; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Stroke - pathology; Stroke - therapy; Vascular diseases and vascular malformations of the nervous system; Human; neonatal stroke; postnatal; Stroke; Nervous system diseases; Brain stem; Cardiovascular disease; Cerebral disorder; Vascular disease; cell transplantation; Newborn; cerebral ischemia; mesenchymal stem cells; Central nervous system disease; Brain ischemia; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/strokeaha.111.000326

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. 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. 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. 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.