Ultrasound Imaging of Brain Organoids Reveals Link Between TBI, Dementia, and ALS

A new study from USC scientists, published in Cell Stem Cell, reveals insights into why traumatic brain injury (TBI) increases the risk of developing neurodegenerative diseases like dementia and ALS. The research, led by Justin Ichida and his team, utilized human patient-derived stem cells to create brain organoids, which are miniature, lab-grown brain structures. These organoids were exposed to high-intensity ultrasound to simulate a TBI. The injured organoids displayed characteristics seen in TBI patients, including nerve cell death and abnormal protein changes, notably in tau and TDP-43, a protein implicated in ALS and frontotemporal dementia. The team found that organoids derived from patients with ALS or frontotemporal dementia showed more pronounced TDP-43 pathology, suggesting a genetic predisposition that may heighten the risk of neurodegenerative diseases after TBI. The most severe damage occurred in excitatory neurons, which are responsible for transmitting signals in the brain. In their search for potential treatments, the researchers identified a gene called KCNJ2, which regulates potassium channels in nerve cells. Inhibiting this gene appeared to protect the organoids from TBI-induced damage, suggesting that targeting KCNJ2 could offer a therapeutic strategy to reduce nerve cell death after brain injuries. This approach may have broad implications, particularly for athletes or individuals at high risk for TBIs. The study was supported by federal grants from the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging, and the Department of Defense.
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