New findings from the University of Kentucky published in
the Journal of Neuroscience demonstrate that there may be ways to
address blood-brain barrier dysfunction in epilepsy.

Until now, it was believed that the cause and effect of
epilepsy was merely based on a dysfunction in the brain’s neurons. However,
recent findings suggest that epilepsy can be caused by many other factors,
including a dysfunctional blood-brain barrier. Essentially, seizures erode
the lining of capillaries in the brain which plays a role in letting nutrients
in and keeping toxins out. This can result in a “leaky” blood-brain
barrier, which leads to more seizures, resulting in epilepsy progression.

Björn Bauer’s lab at the UK College of Pharmacy collaborated
with Sanders-Brown Centre on Aging scientists to conduct research focused on
this barrier leakage. Bauer and colleagues hypothesised that glutamate,
released during seizures, mediates an increase in certain enzymes and activity
levels, thereby contributing to barrier leakage.

Through their research, they found that the neurotransmitter
glutamate, released during seizures, increased the activity of two types of
enzymes, which increased barrier leakage. They also found that blocking the
enzyme cPLA2 and genetically deleting cPLA2 may prevent the changes mentioned
and the associated leakage. This suggests that cPLA2 is responsible for barrier

Since 30% of people with epilepsy do not respond well to
current anti-seizure medications, these findings demonstrate there could be new
ways to treat and manage seizures that currently do not respond well to

The data gathered implies that cPLA2 could be a pharmaceutical
target to repair and normalise barrier dysfunction and improve the treatment of
epilepsy and potentially other neurological disorders that are accompanied by
blood-brain barrier leakage These strategies to repair barrier dysfunction
could be valuable add-on treatments to existing pharmacotherapy.


Reference: Rempe
RG, et al. Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in
Epilepsy. Journal of Neuroscience. Published April 2018.