PMID- 33899499
OWN - NLM
STAT- MEDLINE
DCOM- 20220304
LR  - 20240229
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 38
IP  - 19
DP  - 2021 Oct 1
TI  - 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.
PG  - 2747-2762
LID - 10.1089/neu.2021.0158 [doi]
AB  - 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-beta) 
      (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 beta-amyloid precursor protein (beta-APP) accumulation. In summary, HUCPVCs 
      promoted pericyte-endothelial barrier function that was associated with improved 
      long-term outcome.
FAU - Barretto, Tanya A
AU  - Barretto TA
AD  - Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada.
AD  - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
FAU - Park, Eugene
AU  - Park E
AD  - Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada.
FAU - Telliyan, Tamar
AU  - Telliyan T
AD  - Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada.
FAU - Liu, Elaine
AU  - Liu E
AD  - Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada.
FAU - Gallagher, Denis
AU  - Gallagher D
AD  - CReATe Fertility Centre, Toronto, Ontario, Canada.
FAU - Librach, Clifford
AU  - Librach C
AD  - CReATe Fertility Centre, Toronto, Ontario, Canada.
AD  - Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, 
      Canada.
AD  - Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
FAU - Baker, Andrew
AU  - Baker A
AD  - Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada.
AD  - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
AD  - Department of Critical Care, St. Michael's Hospital, University of Toronto, 
      Toronto, Ontario, Canada.
AD  - Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210609
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier
MH  - Brain Injuries, Traumatic/*complications/*therapy
MH  - Cerebrovascular Disorders/etiology/*therapy
MH  - Disease Models, Animal
MH  - Humans
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells
MH  - Neovascularization, Physiologic/*physiology
MH  - Pericytes
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Umbilical Cord
OTO - NOTNLM
OT  - angiogenic response
OT  - blood-brain barrier dysfunction
OT  - mesenchymal stromal cells
OT  - pericytes
OT  - traumatic brain injury
EDAT- 2021/04/27 06:00
MHDA- 2022/03/05 06:00
CRDT- 2021/04/26 08:45
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2022/03/05 06:00 [medline]
PHST- 2021/04/26 08:45 [entrez]
AID - 10.1089/neu.2021.0158 [doi]
PST - ppublish
SO  - J Neurotrauma. 2021 Oct 1;38(19):2747-2762. doi: 10.1089/neu.2021.0158. Epub 2021 
      Jun 9.