Effect of preconditioning with tPA on the permeability of the blood-brain
barrier. a. Diagram depicting the experimental paradigm to study the
effect of tPA and plasmin (Plm) on the permeability of an in vitro model
of the blood brain barrier (BBB), assembled by brain microvascular
endothelial cells and astrocytes co-cultured on both sides of a 1 μm
pore size insert. b. The in vitro model of the BBB described in A was
exposed to 60 minutes of oxygen and glucose deprivation (OGD) conditions
either 1 (n = 15 inserts assembled with cells from 4 different
cultures), or 3 (n = 12 inserts assembled with cells from 5 different
cultures), or 24 hours (n = 10 inserts assembled with cells from 4
different cultures) after treatment with 5 nM of tPA. A subgroup of
inserts was kept under physiological conditions (n = 16, assembled with
cells from 9 different cultures). Values depict the transendothelial
electrical resistance (TEER) in inserts exposed to OGD conditions
compared to the TEER in inserts maintained under normoxic conditions.
Statistical analysis: one-way ANOVA with Holm-Sidak’s multiple
comparisons test. c. The in vitro model of the BBB described in A was
treated with 5 nM of tPA (n = 13 inserts assembled with cells from 5
different cultures), or vehicle (control; n = 12 inserts assembled with
cell from 5 different cultures) 3 hours before exposure to 60 minutes of
OGD. The permeability to albumin in inserts exposed to OGD conditions
was compared to the permeability of inserts maintained under normoxic
conditions (n = 11, assembled with cells from 5 different cultures).
Statistical analysis: one-way ANOVA with multiple comparisons test. d.
TEER of the in vitro model of the BBB described in A and treated with
either 5 nM of proteolytically inactive tPA (itPA; n = 19 inserts
assembled with cells from 9 different cultures), or vehicle (control;
n = 18 inserts assembled with cells from 9 different cultures) 3 hours
before 60 minutes of OGD. Data were compared to the TEER in inserts
maintained under normoxic conditions (n = 19, assembled with cells from
9 different cultures). Statistical analysis: one-way ANOVA with
Holms-Sidak’s multiple comparisons test. e. Permeability to albumin in
the in vitro model of the BBB described in A and treated with either
5 nM of proteolytically inactive tPA (itPA; n = 18 inserts assembled
with cells from 5 different cultures), or vehicle (control; n = 17
inserts assembled with cells from 6 different cultures) 3 hours before
exposure to 60 minutes of OGD. In each case data were compared to
permeability to albumin in inserts maintained under normoxic conditions
(n = 17, assembled with cells from 6 different cultures). Statistical
analysis: one-way ANOVA with Holms-Sidak’s multiple comparisons test. f.
TEER of the in vitro model of the BBB described in A and treated with
either 100 nM of plasmin (Plm; n = 10 inserts assembled with cells from
5 different cultures), or vehicle (control; n = 10 inserts assembled
with cells from 5 different cultures) three hours before exposure to
60 minutes of OGD. In each case data were compared to the TEER of
inserts maintained under normoxic conditions (n = 9 inserts assembled
with cells from 5 different cultures). Statistical analysis: one-way
ANOVA with Holms-Sidak’s multiple comparisons test.