Injury-induced CTE-like pathology emerges in a human multicellular in vitro brain model and reveals mitochondrial and neurovascular regulation.
Jun, S.; Hinrichsen, D. S.; Kansakar, S. B.; Anamala, C. C.; Teregeyo, J.; Roberts, H. C.; Arrasmith, C. M.; Thielen, M. D.; Liaudanskaya, V.
Show abstract
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease linked to repetitive mild head impacts, but no human-based experimental system exists to study injury-induced CTE-like pathology. Here, we establish a long-lived, human multicellular in vitro brain platform in which controlled mechanical injury induces key cellular features of CTE-like pathology. Injured cultures developed persistent tau phosphorylation, axonal degeneration, chronic inflammation, and metabolic dysfunction without widespread neuronal loss, consistent with progressive pathology rather than acute toxicity. To assess physiological relevance, we integrated transcriptomic profiles from the model with postmortem human CTE brain datasets. This analysis revealed striking convergence at the level of disease-associated modules and pathways, with endothelial cells emerging as critical contributors to CTE-like transcriptional programs. Using this human-based system, we further identified delayed mitochondrial dysfunction as a prominent and sustained feature of injury-induced pathology. Together, these findings establish the first human in vitro platform for studying injury-induced CTE-like pathology and identify neurovascular and mitochondrial regulation as central components of chronic neurodegeneration following repetitive mild brain injury.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype 97%
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury 96%
- Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk 95%
Similar papers in this journal
- Three-dimensional drug screen identifies HDAC inhibitors as therapeutic agents in mTORC1-driven lymphangioleiomyomatosis 94%
- Integrated ERK, PKA, YAP/TAZ, and SHH Signaling Drives Cortical Lineage Diversification and Evolutionary Expansion 94%
- OPTRACE: Optical Imaging Guided Transplantation and Tracking of Cells in the Mouse Brain 94%
Similar papers in this journal
- Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. 95%
- Injectable 3D microcultures enable intracerebral transplantation of mature neurons directly reprogrammed from patient fibroblasts 95%
- Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.