TY - JOUR
T1 - Blast-induced temporal alterations in blood–brain barrier properties in a rodent model
AU - Kawoos, Usmah
AU - Abutarboush, Rania
AU - Gu, Ming
AU - Chen, Ye
AU - Statz, Jonathan K.
AU - Goodrich, Samantha Y.
AU - Ahlers, Stephen T.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The consequences of blast-induced traumatic brain injury (bTBI) on the blood–brain barrier (BBB) and components of the neurovascular unit are an area of active research. In this study we assessed the time course of BBB integrity in anesthetized rats exposed to a single blast overpressure of 130 kPa (18.9 PSI). BBB permeability was measured in vivo via intravital microscopy by imaging extravasation of fluorescently labeled tracers (40 kDa and 70 kDa molecular weight) through the pial microvasculature into brain parenchyma at 2–3 h, 1, 3, 14, or 28 days after the blast exposure. BBB structural changes were assessed by immunostaining and molecular assays. At 2–3 h and 1 day after blast exposure, significant increases in the extravasation of the 40 kDa but not the 70 kDa tracers were observed, along with differential reductions in the expression of tight junction proteins (occludin, claudin-5, zona occluden-1) and increase in the levels of the astrocytic water channel protein, AQP-4, and matrix metalloprotease, MMP-9. Nearly all of these measures were normalized by day 3 and maintained up to 28 days post exposure. These data demonstrate that blast-induced changes in BBB permeability are closely coupled to structural and functional components of the BBB.
AB - The consequences of blast-induced traumatic brain injury (bTBI) on the blood–brain barrier (BBB) and components of the neurovascular unit are an area of active research. In this study we assessed the time course of BBB integrity in anesthetized rats exposed to a single blast overpressure of 130 kPa (18.9 PSI). BBB permeability was measured in vivo via intravital microscopy by imaging extravasation of fluorescently labeled tracers (40 kDa and 70 kDa molecular weight) through the pial microvasculature into brain parenchyma at 2–3 h, 1, 3, 14, or 28 days after the blast exposure. BBB structural changes were assessed by immunostaining and molecular assays. At 2–3 h and 1 day after blast exposure, significant increases in the extravasation of the 40 kDa but not the 70 kDa tracers were observed, along with differential reductions in the expression of tight junction proteins (occludin, claudin-5, zona occluden-1) and increase in the levels of the astrocytic water channel protein, AQP-4, and matrix metalloprotease, MMP-9. Nearly all of these measures were normalized by day 3 and maintained up to 28 days post exposure. These data demonstrate that blast-induced changes in BBB permeability are closely coupled to structural and functional components of the BBB.
UR - http://www.scopus.com/inward/record.url?scp=85102580708&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-84730-8
DO - 10.1038/s41598-021-84730-8
M3 - Article
C2 - 33723300
AN - SCOPUS:85102580708
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5906
ER -