Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic–Ischemic Brain Injury
AbstractCerebral palsy (CP) is a permanent motor disorder that results from brain injury and neuroinflammation during the perinatal period. Mesenchymal stromal cells (MSCs) have been explored as a therapy in multiple adult neuroinflammatory conditions. Our study examined the therapeutic benefits of intranasal delivery of human umbilical cord tissue (UC) derived-MSCs in a rat model of neonatal hypoxic–ischemic (HI) brain injury. To do this, HI was performed on postnatal day 10 Sprague-Dawley rat pups via permanent ligation of the left carotid artery, followed by a hypoxic challenge of 8% oxygen for 90 min. A total of 200,000 UC-MSCs (10 million/kg) were administered intranasally 24 h post-HI. Motor control was assessed after seven days, followed by post-mortem. Analysis included brain immunohistochemistry, gene analysis and serum cytokine measurement. Neonatal HI resulted in brain injury with significant loss of neurons, particularly in the hippocampus. Intranasal administration of UC-MSCs significantly reduced the loss of brain tissue and increased the number of hippocampal neurons. HI significantly upregulated brain inflammation and expression of pro-inflammatory cytokines, while intranasal UC-MSCs significantly reduced markers of neuroinflammation. This study demonstrated that a clinically relevant dose (10 million/kg) of UC-MSCs was neuroprotective following HI by restoring neuronal cell numbers and reducing brain inflammation. Therefore, intranasal delivery of UC-MSCs may be an effective therapy for neonatal brain injury. View Full-Text
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McDonald, C.A.; Djuliannisaa, Z.; Petraki, M.; Paton, M.C.B.; Penny, T.R.; Sutherland, A.E.; Castillo-Melendez, M.; Novak, I.; Jenkin, G.; Fahey, M.C.; Miller, S.L. Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic–Ischemic Brain Injury. Int. J. Mol. Sci. 2019, 20, 2449.
McDonald CA, Djuliannisaa Z, Petraki M, Paton MCB, Penny TR, Sutherland AE, Castillo-Melendez M, Novak I, Jenkin G, Fahey MC, Miller SL. Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic–Ischemic Brain Injury. International Journal of Molecular Sciences. 2019; 20(10):2449.Chicago/Turabian Style
McDonald, Courtney A.; Djuliannisaa, Zlatikha; Petraki, Maria; Paton, Madison C.B.; Penny, Tayla R.; Sutherland, Amy E.; Castillo-Melendez, Margie; Novak, Iona; Jenkin, Graham; Fahey, Michael C.; Miller, Suzanne L. 2019. "Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic–Ischemic Brain Injury." Int. J. Mol. Sci. 20, no. 10: 2449.
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