Nana Efua Andoh
School of Life Sciences
Investigation of the disruption of the blood brain barrier in cerebral
malaria: using an in vitro HBEC-astrocyte tandem model
In CM sequestration of Plasmodium falciparum (Pf) infected red blood cells (PRBC)
in the brain microvasculature, results in disruption of the blood brain barrier (BBB).
Astrocyte activation, observed in patient post-mortem tissue and in the experimental
CM model has been linked to neurological sequelae. We have shown activation of
astrocytes when treated with the PRBC-HBEC (human brain endothelial cells) coculture supernatant (BSP 2015).
We have developed an advanced BBB model composed of human HBEC and
astrocytes grown in tandem on a transwell insert. To investigate the effect of HBECderived soluble factors and cell-associated factors on the BBB, the supernatant and
HBEC lysate were harvested after treatment with PRBC for 20 hours, in separate
experiments (BSP 2015). These supernatants and lysates were added to the
advanced BBB model.
Transendothelial electrical resistance (TEER) of HBEC alone and HBEC-astrocyte
tandem, increased over time with significantly greater TEER in the HBEC-astrocyte
tandem.
PRBC-HBEC supernatant markedly increased permeability of the HBEC monolayer,
but had no effect on the HBEC-astrocyte tandem. A similar, but markedly amplified
effect was observed when cultures of HBEC alone and HBEC-astrocyte tandem
were treated with the HBEC lysates.
These studies suggest that the HBEC-astrocyte tandem culture is considerably more
resistant to HBEC derived factors expressed when PRBC sequester to the BBB.
Together with our previous data (BSP 2015), this suggests that alterations in HBEC
can potentially have a detrimental effect on the astrocytes (located in close proximity
to the HBEC); even in the absence of any significant permeability changes.
Postgraduate Conference 2016
Page 17