implantation-electroencephalogram-electrocardiogram-telemetry-devices

Implantation of Electroencephalogram and Electrocardiogram Telemetry Devices in Neonatal Rabbit Kits

Pathogenic variants in ion channel genes are associated with a high rate of sudden unexpected death in epilepsy (SUDEP). Mechanisms of SUDEP are poorly ...

University of Michigan, Ann Arbor

Pathogenic loss-of-function variants in  are linked to Dravet syndrome (DS). Previous work suggested that neuronal pathfinding defects underlie epileptogenesis and SUDEP in the  null mouse model of DS. We tested this hypothesis by inducing  deletion in adult mice that had developed normally. Epilepsy and SUDEP, which occur by postnatal day 21 in  null animals, were observed within 20 days of induced  deletion in adult mice, suggesting that epileptogenesis in -DS does not result from defective brain development. Thus, the developmental brain defects observed previously in  null mice may model other co-morbidities of DS.

 deletion in adult mice results in seizures and SUDEP.

Brain organoid methods are complicated by multiple rosette structures and morphological variability. We have developed a human brain organoid technique that generates self-organizing, single-rosette cortical organoids (SOSR-COs) with reproducible size and structure at early timepoints. Rather than patterning a 3-dimensional embryoid body, we initiate brain organoid formation from a 2-dimensional monolayer of human pluripotent stem cells patterned with small molecules into neuroepithelium and differentiated to cells of the developing dorsal cerebral cortex. This approach recapitulates the 2D to 3D developmental transition from neural plate to neural tube. Most monolayer fragments form spheres with a single central lumen. Over time, the SOSR-COs develop appropriate progenitor and cortical laminar cell types as shown by immunocytochemistry and single-cell RNA sequencing. At early time points, this method demonstrates robust structural phenotypes after chemical teratogen exposure or when modeling a genetic neurodevelopmental disorder, and should prove useful for studies of human brain development and disease modeling.

Article	Year
deletion in adult mice results in seizures and SUDEP. Annals of clinical and translational neurology\| PubMed ID: 31211177	2019
Deriving early single-rosette brain organoids from human pluripotent stem cells. Stem cell reports\| PubMed ID: 37995702	2023

Jack M. Parent

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