Concussive Injury in Human Forebrain Organoids Alters Neurogenesis and Neuroimmune Signaling

Concussive injury of human forebrain organoids at 25 DIV links severity to cell death and increased TLR4/NF-kappaB-associated neuroimmune signaling in dorsal and ventral regions.

• Why it matters: Rodent TBI models may miss human-specific developmental and molecular injury responses, limiting mechanistic understanding of how concussive injury affects the developing forebrain.
• What they did: The study built a human forebrain organoid (hFBO) injury paradigm, injuring dorsal and ventral organoids at 25 DIV versus 150 DIV and measuring developmental stage-dependent cellular and signaling changes.
• The result: Injury at 25 DIV increased neural proliferation markers alongside severity-scaled cell death, while injury at 150 DIV caused severity-dependent acute intracellular calcium dysregulation.

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