Cerebral palsy (CP) is a neurodevelopmental disorder that results in functional motor impairment and disability in children. CP is characterized by neural injury though many children do not exhibit brain lesions or damage. Advanced structural MRI measures may be more sensitively related to clinical outcomes in this population. Magnetic resonance elastography (MRE) measures the viscoelastic mechanical properties of brain tissue, which vary extensively between normal and disease states, and we hypothesized that the viscoelasticity of brain tissue is reduced in children with CP. Using a global region-of-interest-based analysis, we found that the stiffness of the cerebral gray matter in children with CP is significantly lower than in typically developing (TD) children, while the damping ratio of gray matter is significantly higher in CP. A voxel-wise analysis confirmed this finding, and additionally found stiffness and damping ratio differences between groups in regions of white matter. These results indicate that there is a difference in brain tissue health in children with CP that is quantifiable through stiffness and damping ratio measured with MRE. Understanding brain tissue mechanics in the pediatric CP population may aid in the diagnosis and evaluation of CP.
Cerebral palsy is a neurodevelopmental movement disorder that affects coordination and balance. Therapeutic treatments for balance deficiencies in this population primarily focus on the musculoskeletal system, whereas the neural basis of balance impairment is often overlooked. Magnetic resonance elastography (MRE) is an emerging technique that has the ability to sensitively assess microstructural brain health through in vivo measurements of neural tissue stiffness. Using magnetic resonance elastography, we have previously measured significantly softer grey matter in children with cerebral palsy as compared with typically developing children. To further allow magnetic resonance elastography to be a clinically useful tool in rehabilitation, we aim to understand how brain stiffness in children with cerebral palsy is related to dynamic balance reaction performance as measured through anterior and posterior single-stepping thresholds, defined as the standing perturbation magnitudes that elicit anterior or posterior recovery steps. We found that global brain stiffness is significantly correlated with posterior stepping thresholds ( P = .024) such that higher brain stiffness was related to better balance recovery. We further identified specific regions of the brain where stiffness was correlated with stepping thresholds, including the precentral and postcentral gyri, the precuneus and cuneus, and the superior temporal gyrus. Identifying brain regions affected in cerebral palsy and related to balance impairment can help inform rehabilitation strategies targeting neuroplasticity to improve motor function.
In this study the effect of sequence context on the binding affinity and conformation of DNA dodecamers are explored. The Cre binding site (ACGT) was studied with a number of different flanking sequences. 31P-NMR was used to determine the conformational state (BI/BII ratio) of each step in the phosphate backbone. Importantly, the conformation of the binding site, the center tetrad which was not changed, varied significantly based on the sequence context. Fluorescence titration with the DNA intercalator 7-Aminoactinomycin D was performed to provide biological context to our conformation results. We found that the backbone conformation alone cannot explain the binding affinities in the dodecamers studied. Thus, we turned our attention to base pair dynamics. Preliminary results show that differences in binding affinities in sequences with similar backbone conformations can be explained by differential base pair opening rates.
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