” Many patients fearlessly and generously contribute their surgical specimens for research study to advance our understanding of epilepsy and to establish brand-new and much better therapies,” stated Russin, an assistant teacher of neurological surgical treatment, and associate director of the USC Neurorestoration Center. “These clients know better than anybody the trade-offs involved in the present treatment alternatives, which frequently either do not offer adequate seizure control, or carry really severe cognitive adverse effects.”
Newborn astroglia (green) in brain tissue from human epilepsy clients. Credit: Image by Aswathy Ammothumkandy/Bonaguidi Lab/USC Stem Cell
The surgical specimens afforded a special opportunity for the scientists to study living brain tissue from patients with epilepsy, and to compare its tiny anatomy with post-mortem samples from people without any recognized neurological disease.
In the samples from individuals both with and without epilepsy, the researchers observed newborn nerve cells, including engaging brand-new evidence to the continuous scientific dispute about whether adults retain the ability to produce these cells. In the surgical specimens, the longer the patients had actually experienced seizures, the scarcer these newborn neurons ended up being. More surprisingly, the surgical specimens consisted of a relentless population of immature astroglia that were not observed in the disease-free samples.
Since the brain tissue in the surgical specimens was still alive, the researchers might also use it to grow stem cells in the lab and test their ability to form immature astrocytes and newborn nerve cells. In these experiments, a longer illness duration decreased the ability to form newborn nerve cells and increased the production of immature astroglia, constant with the teams direct observations of the surgical specimens.
The team also studied electrical activity connected to seizures. They discovered suspicious correlations between where electrical activity was localized within the surgical samples, and the area and behavior of the astroglia.
” Normally, astroglia are considered to be supporting cells, because their task is to produce an environment where neurons can thrive,” said Ammothumkandy. “But in patients who have lived for several years with epilepsy, it may be immature astroglia that are adding to both starting and regulating chronic seizures.”
If this is the case, then immature astroglia might be a reliable cell type to target by establishing a totally new class of anti-seizure medications.
” Currently readily available seizure medications tend to target neurons, so medications that act upon immature astroglia might considerably broaden the alternatives for our patients,” stated Liu, a professor of neurological surgical treatment, neurology, and biomedical engineering, director of the USC Neurorestoration Center, and director of the USC Epilepsy Care Consortium. “A brand-new class of drugs might integrate with present medical and surgical methods to manage seizures without aggressive surgical removal of parts of the brain that can be critically essential for discovering, memory and psychological policy.”
Referral: “Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy” 5 April 2022, Nature Neuroscience.DOI: 10.1038/ s41593-022-01044-2.
Bonaguidi, Liu, and Russin initially began the job with pilot financing from an Eli and Edythe Broad Innovation Award, which supports faculty pursuing research partnerships associated with stem cells. The research study brought together clinicians, scientists and engineers from across the Keck School of Medicine of USC– including at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, the USC Neurorestoration Center, and the Zilkha Neurogenetic– the USC Epilepsy Care Consortium, the USC Viterbi School of Engineering, and the USC Davis School of Gerontology, in addition to other universities and medical centers.
About the research study.
Additional co-authors include: Kristine Ravina, Victoria Wolseley, Pen-Ning Yu, Luis Corona, Naibo Zhang, George Nune, Laura Kalayjian, Brian Lee, Dong Song, Theodore W. Berger, Christianne Heck, and Robert H. Chow from USC; Jason A. D. Smith from USC and the University of Texas Southwestern Medical Center; Alexandria N. Tartt from the New York State Psychiatric Institute; J. John Mann, Victoria Arango, and Maura Boldrini from the New York State Psychiatric Institute and Columbia University; and Gorazd B. Rosoklija and Andrew J. Dwork from the New York State Psychiatric Institute, Columbia University, and the Macedonian Academy of Sciences and Arts.
Sixty percent of the funding for this task came from federal grants from the National Institutes of Health (grants R00NS089013, R56AG064077, MH83862, NS090415, MH94888, U01MH098937, MH64168, MH098786, MH090964), and the remaining 40 percent was from non-federal sources including the Donald E. and Delia B. Baxter Foundation, the L.K. Whittier Foundation, The Eli and Edythe Broad Foundation, the USC Neurorestoration Center, the Rudi Schulte Research Institute, the American Foundation for Suicide Prevention (grant SRG-0-129-12), the Brain and Behavior Research Foundation (Independent Investigator Grant 56388), the New York Stem Cell Initiative (grant C029157, C023054), the Dr. Brigitt Rok-Potamkins Foundation, the Morris Stroud III Center for Study of Quality of Life in Health and Aging, and the American Epilepsy Society.
About the Keck School of Medicine of USC.
Founded in 1885, the Keck School of Medicine of USC is one of the nations leading medical organizations, understood for ingenious patient care, clinical discovery, education and neighborhood service. The Keck School faculty are key individuals in training of 1200 resident doctors throughout 70 specialty and subspecialty programs, thus playing a significant role in the education of doctors practicing in Southern California.
Modified cells create an electrical “fire” in patients with epilepsy. Credit: BioRender illustration by Aswathy Ammothumkandy/Bonaguidi Lab/USC Stem Cell
For many years, everybody loses a few brain cells. A research study led by researchers from USC Stem Cell and the USC Neurorestoration Center provides evidence that grownups can renew a minimum of a few of what theyve lost by creating new brain cells, and that this process is dramatically modified in patients with long-lasting epilepsy. The findings are released in Nature Neuroscience.
” Our study is the very first to information the presence of newborn nerve cells and an immature variation of a related cell type, called astroglia, in clients with epilepsy,” said Michael Bonaguidi, an assistant teacher of stem cell biology and regenerative medicine, gerontology, and biomedical engineering at USC. “Our findings furnish unexpected brand-new insights into how immature astroglia may contribute to epilepsy– opening an undiscovered avenue towards the advancement of new anti-seizure medications for millions of people.”
First author Aswathy Ammothumkandy, who is a postdoctoral fellow in the Bonaguidi Lab, and her colleagues worked together with USC neurosurgeons Charles Liu and Jonathan Russin, who often deal with clients with seizures that cant be managed with medication. Drug resistance is especially common with mesial temporal lobe epilepsy, or MTLE, and affects one-third of all patients with this type of the disease. As an outcome, some patients need to undergo surgery to remove the area of the brain, the hippocampus, that causes their seizures.
Over the years, everyone loses a few brain cells. A study led by scientists from USC Stem Cell and the USC Neurorestoration Center provides evidence that adults can renew at least some of what theyve lost by generating brand-new brain cells, and that this procedure is dramatically changed in patients with long-term epilepsy. Author Aswathy Ammothumkandy, who is a postdoctoral fellow in the Bonaguidi Lab, and her coworkers worked together with USC neurosurgeons Charles Liu and Jonathan Russin, who typically treat clients with seizures that cant be managed with medication. In the samples from people both with and without epilepsy, the scientists observed newborn nerve cells, adding engaging brand-new proof to the continuous scientific debate about whether grownups retain the capability to generate these cells. Founded in 1885, the Keck School of Medicine of USC is one of the countrys leading medical institutions, known for ingenious patient care, clinical discovery, education and community service.