Concussive Injury in Human Forebrain Organoids Alters Neurogenesis and Neuroimmune Signaling

Abstract

Traumatic brain injury (TBI) is a major cause of long-term neurological disability, yet the mechanisms underlying human-specific injury responses remain poorly understood. Rodent models of TBI have yielded significant insights into mechanisms and pathophysiology of TBI but may not capture human-specific developmental and molecular responses. Here, we establish a human forebrain organoid (hFBO) injury paradigm to examine developmental stage and region-specific responses to concussive injury. Dorsal and ventral hFBOs, enriched in glutamatergic and GABAergic neurons, respectively, showed progressive physiological maturation with rudimentary firing characteristics at 80 days in vitro (DIV) and spontaneous synaptic activity by 150 DIV. Injury to dorsal and ventral hFBOs at 25 DIV, when neural progenitors dominate, caused cell death that scaled with severity and increased expression of neural proliferation markers and TLR4/NF-{kappa}B associated neuroimmune signaling. Injury to physiologically mature organoids at 150 DIV produced severity-dependent acute intracellular calcium dysregulation. Together, these findings establish a human organoid-based platform that captures developmental stage-dependent neurogenic, molecular, and cellular dysfunction in responses to concussive injury.

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BibTeX RIS

BibTeX

@misc{jaberi2026concussive,
  title = {{Concussive Injury in Human Forebrain Organoids Alters Neurogenesis and Neuroimmune Signaling}},
  author = {Razieh Jaberi and Prince D Okoro and Christopher Taitano-Johnson and Erick M Contreras and Rhea Chidambaram and Piunik Oganian Babakhanins and Iman Noshadi and Nicole I zur Nieden and Vijayalakshmi Santhakumar},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.29.762930},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762930v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Concussive Injury in Human Forebrain Organoids Alters Neurogenesis and Neuroimmune Signaling
AU  - Razieh Jaberi
AU  - Prince D Okoro
AU  - Christopher Taitano-Johnson
AU  - Erick M Contreras
AU  - Rhea Chidambaram
AU  - Piunik Oganian Babakhanins
AU  - Iman Noshadi
AU  - Nicole I zur Nieden
AU  - Vijayalakshmi Santhakumar
PY  - 2026
DA  - 2026/10/29
PB  - bioRxiv
DO  - 10.64898/2026.10.29.762930
UR  - https://www.biorxiv.org/content/10.64898/2026.10.29.762930v1
AB  - Traumatic brain injury (TBI) is a major cause of long-term neurological disability, yet the mechanisms underlying human-specific injury responses remain poorly understood. Rodent models of TBI have yielded significant insights into mechanisms and pathophysiology of TBI but may not capture human-specific developmental and molecular responses. Here, we establish a human forebrain organoid (hFBO) injury paradigm to examine developmental stage and region-specific responses to concussive injury. Dorsal and ventral hFBOs, enriched in glutamatergic and GABAergic neurons, respectively, showed progressive physiological maturation with rudimentary firing characteristics at 80 days in vitro (DIV) and spontaneous synaptic activity by 150 DIV. Injury to dorsal and ventral hFBOs at 25 DIV, when neural progenitors dominate, caused cell death that scaled with severity and increased expression of neural proliferation markers and TLR4/NF-{kappa}B associated neuroimmune signaling. Injury to physiologically mature organoids at 150 DIV produced severity-dependent acute intracellular calcium dysregulation. Together, these findings establish a human organoid-based platform that captures developmental stage-dependent neurogenic, molecular, and cellular dysfunction in responses to concussive injury.
SN  - 2692-8205
ER  -

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