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- Title
Intranasal Delivery of Mesenchymal Stromal Cells Protects against Neonatal Hypoxic–Ischemic Brain Injury.
- Authors
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.
- Abstract
Cerebral 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.
- Subjects
CEREBRAL palsy; STROMAL cells; UMBILICAL cord; CAROTID artery; ENCEPHALITIS
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 10, p2449
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20102449