A surprising brain cleanup reduced epileptic seizures and restored memory
A new study suggests temporal lobe epilepsy may be linked to early aging of certain brain cells. When researchers removed these aging cells in mice, seizures dropped, memory improved, and some animals avoided epilepsy altogether. The treatment used drugs already known to science, raising the possibility of quicker translation to people. The results offer new hope for patients who do not respond to existing medications.
Temporal lobe epilepsy causes repeated seizures and often interferes with memory and thinking. New research now suggests that this condition is also tied to early aging in certain brain cells. Scientists at Georgetown University Medical Center report that eliminating these aging cells in mice led to fewer seizures, better memory, and protection against epilepsy in some animals. The aging cells were removed using both genetic approaches and drug-based treatments.
The National Institutes of Health (NIH)-funded study was published on December 22 in the journal Annals of Neurology.
A New Approach for Drug Resistant Epilepsy
"A third of individuals living with epilepsy don't achieve freedom from seizures with current medications." says senior author Patrick A. Forcelli, Ph.D., professor and chair of Georgetown School of Medicine's Department of Pharmacology & Physiology and the Jerome H. Fleisch & Marlene L. Cohen Endowed Professor of Pharmacology. "Our hope is that senotherapy, which involves using medications to remove senescent, or aging cells, could potentially minimize the need for surgery and/or improve outcomes after surgery."
Temporal lobe epilepsy (TLE) can arise from many underlying causes. These include head injuries related to trauma or stroke, infections such as meningitis, brain tumors, abnormal blood vessel structures, and inherited genetic conditions. TLE is the most common form of epilepsy that does not respond well to medication and affects roughly 40% of people with epilepsy.
Aging Support Cells Found in Human Brain Tissue
To explore the biology behind TLE, researchers examined donated human brain tissue that had been surgically removed from the temporal lobes of epilepsy patients. When compared with autopsy samples from individuals without epilepsy, the tissue from TLE patients showed a five-fold increase in senescent glial cells. Glial cells help maintain and protect neurons, although they do not generate electrical signals themselves.
Mouse Experiments Show Reduced Seizures and Memory Gains
Based on the findings in human tissue, the team investigated whether a similar buildup of aging cells occurred in a mouse model designed to mimic TLE. Within two weeks after the brain injury that initiated epilepsy in the mice, the researchers detected clear increases in markers of cellular aging at both the gene and protein levels.
When treatments were used to remove the aging cells, the effects were substantial. The number of senescent cells dropped by about 50%. The treated mice performed normally on maze-based memory tests, experienced fewer seizures, and about one-third were completely protected from developing epilepsy.
Repurposed Drugs With Known Safety Profiles
The drug treatment tested in the mice combined dasatinib and quercetin. Dasatinib is a targeted therapy currently used to treat leukemia. Quercetin is a plant flavonoid found in fruits, vegetables, tea, and wine that can act as a powerful antioxidant and have anti-inflammatory properties. This drug combination has been widely used in animal studies to eliminate senescent cells across several disease models.