Vascular Dysfunction after Modeled Traumatic Brain Injury Is Preserved with Administration of Umbilical Cord Derived Mesenchymal Stromal Cells and Is Associated with Modulation of the Angiogenic Response
Autor: | Tamar Telliyan, Elaine Liu, Eugene Park, Denis Gallagher, Clifford Librach, Tanya Barretto, Andrew J. Baker |
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Rok vydání: | 2021 |
Předmět: |
Male
030506 rehabilitation Pathology medicine.medical_specialty Traumatic brain injury Neovascularization Physiologic Mesenchymal Stem Cell Transplantation Umbilical cord Umbilical Cord Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Brain Injuries Traumatic medicine Animals Humans business.industry Mesenchymal stem cell food and beverages Mesenchymal Stem Cells medicine.disease Rats Cerebrovascular Disorders Disease Models Animal medicine.anatomical_structure nervous system Blood-Brain Barrier Neurology (clinical) Stem cell 0305 other medical science business Pericytes 030217 neurology & neurosurgery |
Zdroj: | Journal of neurotrauma. 38(19) |
ISSN: | 1557-9042 |
Popis: | Vascular dysfunction arising from blood-brain barrier (BBB) breakdown after traumatic brain injury (TBI) can adversely affect neuronal health and behavioral outcome. Pericytes and endothelial cells of the neurovascular unit (NVU) function collectively to maintain strict regulation of the BBB through tight junctions. Secondary injury mechanisms, such as pro-angiogenic signals that contribute to pericyte loss, can prolong and exacerbate primary vascular injury. Human umbilical cord perivascular cells (HUCPVCs) are a source of mesenchymal stromal cells (MSCs) that have been shown to reduce vascular dysfunction after neurotrauma. We hypothesized that the perivascular properties of HUCPVCs can reduce vascular dysfunction after modeled TBI by preserving the pericyte-endothelial interactions. Rats were subjected to a moderate fluid percussion injury (FPI) and intravenously infused with 1,500,000 HUCPVCs post-injury. At acute time points (24 h and 48 h) quantitative polymerase chain reaction (qPCR) analysis demonstrated that the gene expression of angiopoietin-2 was increased with FPI and reduced with HUCPVCs. Immunofluorescent assessment of RECA-1 (endothelial cells) and platelet-derived growth factor receptors (PDGFR-β) (pericytes) revealed that capillary and pericyte densities as well as the co-localization of the two cells were decreased with FPI and preserved with HUCPVC administration. These acute HUCPVC-mediated protective effects were associated with less permeability to Evan's blue dye and increased expression of the tight junction occludin, suggesting less vascular leakage. Further, at 4 weeks post-injury, HUCPVC administration was associated with reduced anxiety and decreased β-amyloid precursor protein (β-APP) accumulation. In summary, HUCPVCs promoted pericyte-endothelial barrier function that was associated with improved long-term outcome. |
Databáze: | OpenAIRE |
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