a feline-specific blood brain barrier. feline immunodeficiency virus lentivirus natural infection in...
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A Feline-specific Blood Brain Barrier
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Feline Immunodeficiency Virus
• Lentivirus• Natural infection in
cats worldwide• Induces disease• Animal model of HIV
infection in man
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Feline immunodeficiency virus infection- a model of HIV-1 induced encephalitis
• HIV and FIV neurotropic• Early infection of CNS• Neuroinflammation and degeneration• Limited opportunities to study early infection• Requires well-evaluated animal
models» SIV
» FIV
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Ryan et al, J Neurovirol 2005
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Aims
– To investigate the ability of cell-free & cell-associated FIV to cross the in vitro BBB, and the effect of inflammatory cytokines on this process.
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The Blood-Brain Barrier
Blood Vessel
(Made from Endothelial Cells)
Astrocyte
TJs
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Assembly of the Blood Brain Barrier Model
Plate
Transwell
Bottom Chamber
Top Chamber
Fletcher et al (2005) Vet Immuno Immunopathol
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Assembly of the Blood Brain Barrier Model
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
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Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
FIV-infected T
cells
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Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
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Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
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Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
The effect of cell-free FIV on the feline BBB model
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A: Mya-1 apicalB: FIV Mya-1 apicalC: Mya-1 apical; TNF basolateralD: FIV Mya-1 apical; TNF basolateralE: Mya-1 apical; TNF apicalF: FIV Mya-1 apical; TNF apicalG: FIV Mya-1 apical and basolateralH: FIV Mya-1 apical and basolateral; TNF
basolateral
Top Chamber (Blood)
Bottom Chamber (Brain)
EndothelialCells
Astrocytes
FIV-infected T cells
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**p<0.05
***p<0.0001
2-tailed Unpaired t testA: Mya-1 apicalB: FIV Mya-1 apicalC: Mya-1 apical; TNF basolateralD: FIV Mya-1 apical; TNF basolateralE: Mya-1 apical; TNF apicalF: FIV Mya-1 apical; TNF apicalG: FIV Mya-1 apical and basolateralH: FIV Mya-1 apical and basolateral; TNF basolateral
Transmigration of Mya-1 cellsacross the in vitro BBB
A B C D E F G H0
25
50
75
100
Tra
nsm
igra
ted
Mya
-1
cell
s (x
104 )
***
*****
******
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Permeability of BBB Models toFD-4 following Mya-1
Transmigration
1 2 3 4 5 6 7 80.0×10 -00
5.0×10 -05
1.0×10 -04
1.5×10 -04
Pap
p(c
m/s
)**
**p<0.05
2-tailed unpaired t-test1. BBB2. Mya-1 apical3. Mya-1 apical; TNF basolateral4. FIV Mya-1 apical; TNF basolateral5. Mya-1 apical; TNF apical6. FIV Mya-1 apical; TNF apical7. FIV Mya-1 apical and basolateral8. FIV Mya-1 apical and basolateral; TNF basolateral
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Primary Cell Lines
Brain endothelial cells
Astrocytes
Microglia
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Histopathological evaluations of tissues from exposure studies
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