A traumatic brain injury (TBI) can quadruple your risk for developing dementia and increase your chances of developing neurodegenerative diseases such as ALS. In a new study published in Cell Stem Cell, scientists use lab-grown human brain structures known as organoids to offer insights into why this is the case and how to mitigate the risk.

In the study, researchers used human patient-derived stem cells to grow rudimentary brain structures known as organoids in the lab. They then injured these organoids with high-intensity ultrasound waves. 

The injured organoids showed some of the same features seen in TBI patients, including nerve cell death and pathological changes in tau proteins, as well as in a protein called TDP-43. 

The scientists found that the pathological changes in TDP-43 were more prevalent in organoids derived from patients with ALS or frontotemporal dementia, making their nerve cells more suspectable to dysfunction and death following injury. This suggests that TBI might increase the risk of developing these diseases even more for patients with a genetic predisposition. The worst injuries were sustained by nerve cells that share information—called excitatory neurons—located in the deep layers of the organoids.

In their search for ways to protect these neurons against the effects of TBI, the scientists identified a gene called KCNJ2, which contains instructions for making channels that selectively allow potassium to pass through the cell membrane, helping to enable muscle contraction and relaxation. Inhibiting this gene had a protective effect on organoids derived from patients with and without ALS, as well as on mice, following a TBI. 

“Targeting KCNJ2 may reduce the death of nerve cells after TBI,” said the principal investigator. “This could have potential as either a post-injury treatment or as a prophylactic for athletes and others at high risk for TBI.”

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00085-7

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fkcnj2-inhibition&filter=22