Brain-repair discovery could lead to new epilepsy treatments

Date:
July 23, 2021
Source:
University of Virginia Health System
Summary:
Researchers have discovered a previously unknown repair process
in the brain that they hope could be harnessed and enhanced to
treat seizure- related brain injuries.



FULL STORY ========================================================================== University of Virginia School of Medicine researchers have discovered a previously unknown repair process in the brain that they hope could be harnessed and enhanced to treat seizure-related brain injuries.


========================================================================== Common seizure-preventing drugs do not work for approximately a third of epilepsy patients, so new and better treatments for such brain injuries
are much needed. UVA's discovery identifies a potential avenue, one
inspired by the brain's natural immune response.

Using high-powered imaging, the researchers were able to see, for the
first time, that immune cells called microglia were not just removing
damaged material after experimental seizures but actually appeared to
be healing damaged neurons.

"There has been mounting generic support for the idea that microglia could
be used to ameliorate seizures, but direct, visualized evidence for how
they could do this has been lacking," said researcher Ukpong B. Eyo, PhD,
of UVA's Department of Neuroscience, the UVA Brain Institute and UVA's
Center for Brain Immunology and Glia (BIG). "Our results indicate that microglia may not be simply clearing debris but providing structural
support for neuronal integrity that may have implications even beyond
the scope of seizures and epilepsy." A Surprising Response to Seizures
The new findings come from a collaboration of scientists at UVA, Mayo
Clinic and Rutgers University. They used an advanced imaging technique
called two- photon microscopy to examine what happened in the brains of
lab mice after severe seizures. What they saw was strange and unexpected.

Rather than simply cleaning up debris, the microglia began forming
pouches.

These pouches didn't swallow up damaged material, as many immune cells do.

Instead, they began tending to swollen dendrites -- the branches of
nerve cells that transmit nerve impulses. They weren't removing, the
scientists realized; they appeared to be healing.

These odd little pouches -- the scientists named them "microglial process pouches" -- stuck around for hours. They often shrank, but they were
clearly doing something beneficial because the dendrites they targeted
ended up looking better and healthier than those they didn't.

"We did not find microglia to be 'eating' the neuronal elements in this context," Eyo said. "Rather, we saw a strong correlation between these interactions and a structural resolution of injured neurons suggestive of
a 'healing' process." The new insights into the brain's immune response
points scientists in promising new directions. "Although these findings
are exciting, there is yet a lot to follow-up on them. For example,
the precise mechanisms that regulate the interactions remain to be
identified. Moreover, at present, the 'healing' feature is suggested
from correlational results and more definitive studies are required to
certify the nature of the 'healing,'" Eyo said. "If these questions can
be answered, they will provide a rationale for developing approaches to
enhance this process ... in seizure contexts." Eyo has already received
two grants totaling almost $5 million from the National Institutes of
Health to continue his study of microglia. The funding will allow him
to study how the immune cells help regulate vascular function, which
could be important in diseases such as Alzheimer's, and their role in brain-hyperactivity disorders such as febrile seizures that can trigger epilepsy.

"With this new funding, we are eager to clarify roles for
microglia in seizure disorders and vascular function,"
he said. "UVA's continued investment is neuroscience
research provides a suitable home for our lab's research." ========================================================================== Story Source: Materials provided by
University_of_Virginia_Health_System. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Ukpong B. Eyo, Koichiro Haruwaka, Mingshu Mo, Antony Brayan Campos-
Salazar, Lingxiao Wang, Xenophon S. Speros, Sruchika Sabu,
Pingyi Xu, Long-Jun Wu. Microglia provide structural resolution
to injured dendrites after severe seizures. Cell Reports, 2021;
35 (5): 109080 DOI: 10.1016/ j.celrep.2021.109080 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210723105304.htm

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