A Felinespecific Blood Brain Barrier

1
A Feline-specific Blood Brain Barrier
2
Feline Immunodeficiency Virus

• Lentivirus
• Natural infection in cats worldwide
• Induces disease
• Animal model of HIV infection in man

3
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

4
(No Transcript)
5
(No Transcript)
6
Ryan et al, J Neurovirol 2005
7
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.

8
(No Transcript)
9
The Blood-Brain Barrier
10
Assembly of the Blood Brain Barrier Model
Fletcher et al (2005) Vet Immuno Immunopathol
11
Assembly of the Blood Brain Barrier Model
Top Chamber (Blood)
Bottom Chamber (Brain)
12
Top Chamber (Blood)
Endothelial Cells
Astrocytes
Bottom Chamber (Brain)
13
Top Chamber (Blood)
Endothelial Cells
Astrocytes
Bottom Chamber (Brain)
14
Top Chamber (Blood)
Endothelial Cells
Astrocytes
Bottom Chamber (Brain)
15
The effect of cell-free FIV on the feline BBB
model
Top Chamber (Blood)
Endothelial Cells
Astrocytes
Bottom Chamber (Brain)
16

• A Mya-1 apical
• B FIV Mya-1 apical
• C Mya-1 apical TNF basolateral
• D FIV Mya-1 apical TNF basolateral
• E Mya-1 apical TNF apical
• F FIV Mya-1 apical TNF apical
• G FIV Mya-1 apical and basolateral
• H FIV Mya-1 apical and basolateral TNF
  basolateral

17
plt0.05 plt0.0001 2-tailed Unpaired t test
A Mya-1 apical B FIV Mya-1 apical C Mya-1
apical TNF basolateral D FIV Mya-1 apical TNF
basolateral E Mya-1 apical TNF apical F FIV
Mya-1 apical TNF apical G FIV Mya-1 apical and
basolateral H FIV Mya-1 apical and basolateral
TNF basolateral
18
plt0.05 2-tailed unpaired t-test

• BBB
• Mya-1 apical
• Mya-1 apical TNF basolateral
• FIV Mya-1 apical TNF basolateral
• Mya-1 apical TNF apical
• FIV Mya-1 apical TNF apical
• FIV Mya-1 apical and basolateral
• FIV Mya-1 apical and basolateral TNF
  basolateral

19
Primary Cell Lines
Brain endothelial cells
Astrocytes
Microglia
20
Histopathological evaluations of tissues from
exposure studies
21
(No Transcript)