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Biology subjects

Strother, L.

Publications and source records attributed to Strother, L..

3 recordsLinked to original sources

MRI-to-Synthetic 3D Gel Brain: Proof-of-Concept Fabrication For Intra-Parenchymal Diffusion Studies

Bioprinting technologies utilize hydrogel-based biomaterials to more accurately depict in vivo physical conditions within in vitro studies, yet, manufacturing the human brain from soft, poroelastic hydrogels remains a fundamental challenge. Conventional manufacturing routes to fabricate hydrogel brain models using techniques, i.e., 3D printing, seems challenging. This study aims to demonstrate an inverse replica molding fabrication technique that can overcome these challenges while maintaining the complex shape of an individual subjects brain in a miniaturized model--allowing for a more robust hydrogel model that can capture the interactions between diffusing molecules and brain boundaries. This is done by taking a subjects magnetic resonance imaging (MRI) scan and reconstructing the outer pial surface into a mesh surface. The mesh was then converted to an STL and printed out using an extrusion printer. A silicon mold was made from this print into which agarose was gelled. Once fully gelated, the synthetic gel brain was then carefully removed. Two infusion trials were run in the gel brain, each using a different infusion site. Then a diffusion profile was established and compared to a simple gel infusion model. The result shows different diffusion profiles at each location and between the simple and complex models. This model can better represent the interference the complex shape of the brain has on particle movement compared to simple gel models.

bioengineering↗

In Silico, Brain Mesh Platform for Computing Topographic Dependent Internal Facets

Individualized and anatomically correct computational models of the brain can be leveraged to improve knowledge of drug dispersal following simulation of drug delivery. Using a patients magnetic resonance image (MRI) scans, we were able to reconstruct the pial surface of the brain of the left hemisphere with strong anatomic accuracy. We then established the major internal features, including the lateral ventricle, a tumor, and drug delivery catheters. These were able to include relevant tissue characteristics such as porosity and permeability in the Multiphysics platform COMSOL to create a platform for brain modeling. To test the performance of this platform, we simulated direct drug infusion in both a healthy patient brain and a diseased patient model, focusing on glioblastoma (GBM). Using this platform, we simulated perturbed convection enhanced delivery of a cancer medication (similar to temozolomide (TMZ) but modeled using methylene blue) to the tumor. Consequently, with our patient derived model, we are able to simulate solute dispersal and fluid flow representative of in vivo conditions.

bioengineering↗

A role for thalamic projection GABAergic neurons in circadian responses to light

The thalamus is an important hub for sensory information and participates in sensory perception, regulation of attention, arousal and sleep. These functions are executed primarily by glutamatergic thalamocortical neurons that extend axons to the cortex and initiate cortico-thalamocortical connectional loops. However, the thalamus also contains projection GABAergic neurons that do not engage in direct communication with the cortex. Here, we have harnessed recent insight into the development of the intergeniculate (IGL), the ventrolateral geniculate (LGv) and the perihabenula (pHB) to specifically target and manipulate thalamic projection GABAergic neurons in female and male mice. Our results show that thalamic GABAergic neurons of the IGL and LGv receive retinal input from diverse classes of ipRGCs, but not from the M1 ipRGC type, while those in the pHB lack direct retinal input. We describe the synergistic role of the photoreceptor melanopsin and the thalamic neurons of the IGL/LGv in circadian entrainment to dim light. We identify a requirement for the thalamic IGL/LGv in the rapid changes in vigilance states associated with circadian light transitions. Furthermore, we map a previously undescribed thalamic network of developmentally related GABAergic neurons in the IGL/LGv complex and the pHB potentially involved in light-dependent mood regulation. Significance statementThe intergeniculate leaflet and ventral geniculate nucleus are part of the extended circadian system and mediate some non-image-forming visual functions. Here we show that each of these structures has a thalamic (dorsal) as well as prethalamic (ventral) developmental origin. We map the retinal input to thalamus-derived cells in the IGL/LGv complex and discover that while ipRGC input is dominant, this is not likely to originate from M1-ipRGCs. We describe the extent of similarity in synaptic input to developmentally related cells in the IGL/LGv and in the perihabenula nucleus (pHB). We implicate thalamic cells in the IGL/LGv in vigilance state transitions at circadian light changes and in overt behavioural entrainment to dim light, the latter exacerbated by concomitant loss of melanopsin expression.

neuroscience↗