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Glioblastoma multiforme (GBM), one of the deadliest forms of human cancer, is characterized by its high infiltration capacity, partially regulated by the neural extracellular matrix (ECM). A major limitation in developing effective treatments is the lack of in vitro models that mimic features of GBM migration highways. Ideally, these models would permit tunable control of mechanics and chemistry to allow the unique role of each of these components to be examined. To address this need, we developed aligned nanofiber biomaterials via core-shell electrospinning that permit systematic study of mechanical and chemical influences on cell adhesion and migration. These models mimic the topography of white matter tracts, a major GBM migration 'highway'. To independently investigate the influence of chemistry and mechanics on GBM behaviors, nanofiber mechanics were modulated by using different polymers (i.e., gelatin, poly(ethersulfone), poly(dimethylsiloxane)) in the 'core' while employing a common poly(ε-caprolactone) (PCL) 'shell' to conserve surface chemistry. These materials revealed GBM sensitivity to nanofiber mechanics, with single cell morphology (Feret diameter), migration speed, focal adhesion kinase (FAK) and myosin light chain 2 (MLC2) expression all showing a strong dependence on nanofiber modulus. Similarly, modulating nanofiber chemistry using extracellular matrix molecules (i.e., hyaluronic acid (HA), collagen, and Matrigel) in the 'shell' material with a common PCL 'core' to conserve mechanical properties revealed GBM sensitivity to HA; specifically, a negative effect on migration. This system, which mimics the topographical features of white matter tracts, should allow further examination of the complex interplay of mechanics, chemistry, and topography in regulating brain tumor behaviors.
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http://dx.doi.org/10.1016/j.biomaterials.2013.03.069 | DOI Listing |
Hum Brain Mapp
December 2024
Department of Psychology, Northeastern University, Boston, Massachusetts, USA.
Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.
View Article and Find Full Text PDFEClinicalMedicine
September 2024
Department of Medicine, University of Cambridge, Cambridge, UK.
Background: Even patients with normal computed tomography (CT) head imaging may experience persistent symptoms for months to years after mild traumatic brain injury (mTBI). There is currently no good way to predict recovery and triage patients who may benefit from early follow-up and targeted intervention. We aimed to assess if existing prognostic models can be improved by serum biomarkers or diffusion tensor imaging metrics (DTI) from MRI, and if serum biomarkers can identify patients for DTI.
View Article and Find Full Text PDFHum Brain Mapp
December 2024
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is a circuit-based treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear.
View Article and Find Full Text PDFGlia
December 2024
Faculty of Medicine, Experimental Epilepsy Research, Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter boundary or a transmantle sign indicating abnormal white matter myelination. Recently, we have shown that myelination is also compromised in the gray matter of FCD IIa of the temporal lobe.
View Article and Find Full Text PDFBrain Res
December 2024
Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address:
The corpus callosum (CC) is the largest white matter fiber bundle connecting the two hemispheres, facilitating interhemispheric integration and hemispheric specialization. Neuroimaging studies have identified the CC as a marker for aging and various neuropsychiatric disorders. However, high-resolution imaging and detailed lifespan characterizations of CC morphology and connectivity remain limited.
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