image: This is the representative immunostaining for MMP-2 (left), MMP-9 (middle) and the negative control (right; overlay of green, blue and transmitted light channels) in isolated rat brain capillaries. MMPs are shown in green; nuclei were counterstained with DAPI (blue). view more
Credit: Rempe et al., <i>JNeurosci</i> (2018)
Blocking the activity of an enzyme that interferes with the blood-brain barrier, contributing to the generation of recurring seizures, may provide a new way to treat epilepsy that is resistant to anti-seizure drugs, according to a study of rats and mice published in JNeurosci.
One-third of people with epilepsy, one of the most common neurological disorders, do not respond well to current treatments for managing seizures. Part of this challenge is that seizures erode the lining of capillaries in the brain that let nutrients in and keeps toxins out. A "leaky" blood-brain barrier, in turn, leads to more seizures. Understanding how this cycle occurs is necessary in order to develop strategies to plug the leak.
In their study of rodent brain capillaries, Björn Bauer and colleagues identified a seizure-triggered pathway that contributes to blood-brain barrier dysfunction in epilepsy. The neurotransmitter glutamate, released during seizures, increased the activity of two types of enzymes belonging to a group called matrix-metalloproteinase (MMP-2, MMP-9) and degraded the tightly-packed proteins that form a critical component of the blood-brain barrier. Blocking another enzyme called cytosolic phospholipase A2 (cPLA2) in rats with induced seizures and genetically deleting cPLA2 in mice prevented these changes and the associated capillary leakage.
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Article: Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy
DOI: https://doi.org/10.1523/JNEUROSCI.2751-17.2018
Corresponding author: Björn Bauer (University of Kentucky, Lexington, USA), bjoern.bauer@uky.edu
About JNeurosci
JNeurosci, the Society for Neuroscience's first journal, was launched in 1981 as a means to communicate the findings of the highest quality neuroscience research to the growing field. Today, the journal remains committed to publishing cutting-edge neuroscience that will have an immediate and lasting scientific impact, while responding to authors' changing publishing needs, representing breadth of the field and diversity in authorship.
About The Society for Neuroscience
The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.