A tabletop blast device for the study of the long-term consequences of traumatic brain injury on brain organoids.

Abstract

Traumatic brain injury (TBI) is the leading environmental risk factor for neurodegenerative diseases, yet its molecular link to chronic neurodegeneration is unclear. While animal models of TBI are commonly used, emerging research suggests that induced pluripotent stem cell (iPSC)-derived brain organoids offer a promising human-specific alternative, particularly for studying processes like cryptic exon splicing. However, widespread use has been limited by methodological variability and the need for expensive and specialized equipment. To address these challenges, we developed a tabletop blast device capable of delivering highly reproducible pressure waves via a gravity-based pressure chamber. We validated the applicability of our approach by assessing the short- and long-term consequences of mechanical stress on brain organoids after pressure wave exposure. Our approach provides a controllable and reproducible method to apply complex pressure cycles on brain organoids, enabling broader accessibility for studying the mechanistic links between TBI and neurodegeneration in a human-relevant context.