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A Feline-specific Blood Brain Barrier. Feline Immunodeficiency Virus Lentivirus Natural infection in cats worldwide Induces disease Animal model of HIV.

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Presentation on theme: "A Feline-specific Blood Brain Barrier. Feline Immunodeficiency Virus Lentivirus Natural infection in cats worldwide Induces disease Animal model of HIV."— Presentation transcript:

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

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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.

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9 The Blood-Brain Barrier Blood Vessel (Made from Endothelial Cells) Astrocyte TJs

10 Assembly of the Blood Brain Barrier Model Plate Transwell Bottom Chamber Top Chamber  Fletcher et al (2005) Vet Immuno Immunopathol

11 Assembly of the Blood Brain Barrier Model Top Chamber (Blood) Bottom Chamber (Brain) Endothelial Cells Astrocytes

12 Top Chamber (Blood) Bottom Chamber (Brain) Endothelial Cells Astrocytes FIV-infected T cells

13 Top Chamber (Blood) Bottom Chamber (Brain) Endothelial Cells Astrocytes

14 Top Chamber (Blood) Bottom Chamber (Brain) Endothelial Cells Astrocytes

15 Top Chamber (Blood) Bottom Chamber (Brain) Endothelial Cells Astrocytes The effect of cell-free FIV on the feline BBB model

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 **p<0.05 ***p<0.0001 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 **p<0.05 2-tailed unpaired t-test 1.BBB 2.Mya-1 apical 3.Mya-1 apical; TNF basolateral 4.FIV Mya-1 apical; TNF basolateral 5.Mya-1 apical; TNF apical 6.FIV Mya-1 apical; TNF apical 7.FIV Mya-1 apical and basolateral 8.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

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