Publications by authors named "Sydney E Sneed"

4 Publications

  • Page 1 of 1

Detecting functional connectivity disruptions in a translational pediatric traumatic brain injury porcine model using resting-state and task-based fMRI.

Sci Rep 2021 Jun 11;11(1):12406. Epub 2021 Jun 11.

Department of Physics and Astronomy, Franklin College of Arts and Sciences, University of Georgia, 500 D.W. Brooks Drive Rm 119, Athens, GA, 30602, USA.

Functional magnetic resonance imaging (fMRI) has significant potential to evaluate changes in brain network activity after traumatic brain injury (TBI) and enable early prognosis of potential functional (e.g., motor, cognitive, behavior) deficits. In this study, resting-state and task-based fMRI (rs- and tb-fMRI) were utilized to examine network changes in a pediatric porcine TBI model that has increased predictive potential in the development of novel therapies. rs- and tb-fMRI were performed one day post-TBI in piglets. Activation maps were generated using group independent component analysis (ICA) and sparse dictionary learning (sDL). Activation maps were compared to pig reference functional connectivity atlases and evaluated using Pearson spatial correlation coefficients and mean ratios. Nonparametric permutation analyses were used to determine significantly different activation areas between the TBI and healthy control groups. Significantly lower Pearson values and mean ratios were observed in the visual, executive control, and sensorimotor networks for TBI piglets compared to controls. Significant differences were also observed within several specific individual anatomical structures within each network. In conclusion, both rs- and tb-fMRI demonstrate the ability to detect functional connectivity disruptions in a translational TBI piglet model, and these disruptions can be traced to specific affected anatomical structures.
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http://dx.doi.org/10.1038/s41598-021-91853-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196021PMC
June 2021

Exploring the predictive value of lesion topology on motor function outcomes in a porcine ischemic stroke model.

Sci Rep 2021 Feb 15;11(1):3814. Epub 2021 Feb 15.

Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.

Harnessing the maximum diagnostic potential of magnetic resonance imaging (MRI) by including stroke lesion location in relation to specific structures that are associated with particular functions will likely increase the potential to predict functional deficit type, severity, and recovery in stroke patients. This exploratory study aims to identify key structures lesioned by a middle cerebral artery occlusion (MCAO) that impact stroke recovery and to strengthen the predictive capacity of neuroimaging techniques that characterize stroke outcomes in a translational porcine model. Clinically relevant MRI measures showed significant lesion volumes, midline shifts, and decreased white matter integrity post-MCAO. Using a pig brain atlas, damaged brain structures included the insular cortex, somatosensory cortices, temporal gyri, claustrum, and visual cortices, among others. MCAO resulted in severely impaired spatiotemporal gait parameters, decreased voluntary movement in open field testing, and higher modified Rankin Scale scores at acute timepoints. Pearson correlation analyses at acute timepoints between standard MRI metrics (e.g., lesion volume) and functional outcomes displayed moderate R values to functional gait outcomes. Moreover, Pearson correlation analyses showed higher R values between functional gait deficits and increased lesioning of structures associated with motor function, such as the putamen, globus pallidus, and primary somatosensory cortex. This correlation analysis approach helped identify neuroanatomical structures predictive of stroke outcomes and may lead to the translation of this topological analysis approach from preclinical stroke assessment to a clinical biomarker.
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http://dx.doi.org/10.1038/s41598-021-83432-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884696PMC
February 2021

Magnetic Resonance Imaging and Gait Analysis Indicate Similar Outcomes Between Yucatan and Landrace Porcine Ischemic Stroke Models.

Front Neurol 2020 21;11:594954. Epub 2021 Jan 21.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.

The Stroke Therapy Academic Industry Roundtable (STAIR) has recommended that novel therapeutics be tested in a large animal model with similar anatomy and physiology to humans. The pig is an attractive model due to similarities in brain size, organization, and composition relative to humans. However, multiple pig breeds have been used to study ischemic stroke with potentially differing cerebral anatomy, architecture and, consequently, ischemic stroke pathologies. The objective of this study was to characterize brain anatomy and assess spatiotemporal gait parameters in Yucatan (YC) and Landrace (LR) pigs pre- and post-stroke using magnetic resonance imaging (MRI) and gait analysis, respectively. Ischemic stroke was induced via permanent middle cerebral artery occlusion (MCAO). MRI was performed pre-stroke and 1-day post-stroke. Structural and diffusion-tensor sequences were performed at both timepoints and analyzed for cerebral characteristics, lesion diffusivity, and white matter changes. Spatiotemporal and relative pressure gait measurements were collected pre- and 2-days post-stroke to characterize and compare acute functional deficits. The results from this study demonstrated that YC and LR pigs exhibit differences in gross brain anatomy and gait patterns pre-stroke with MRI and gait analysis showing statistical differences in the majority of parameters. However, stroke pathologies in YC and LR pigs were highly comparable post-stroke for most evaluated MRI parameters, including lesion volume and diffusivity, hemisphere swelling, ventricle compression, caudal transtentorial and foramen magnum herniation, showing no statistical difference between the breeds. In addition, post-stroke changes in velocity, cycle time, swing percent, cadence, and mean hoof pressure showed no statistical difference between the breeds. These results indicate significant differences between pig breeds in brain size, anatomy, and motor function pre-stroke, yet both demonstrate comparable brain pathophysiology and motor outcomes post-stroke. The conclusions of this study suggest pigs of these different breeds generally show a similar ischemic stroke response and findings can be compared across porcine stroke studies that use different breeds.
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http://dx.doi.org/10.3389/fneur.2020.594954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859633PMC
January 2021

An Adolescent Porcine Model of Voluntary Alcohol Consumption Exhibits Binge Drinking and Motor Deficits in a Two Bottle Choice Test.

Alcohol Alcohol 2021 Apr;56(3):266-274

Regenerative Bioscience Center, University of Georgia, 425 River Road, Athens, GA, 30602, USA.

Aims: Alcohol is the most commonly abused substance leading to significant economic and medical burdens. Pigs are an attractive model for studying alcohol abuse disorder due to the comparable alcohol metabolism and consumption behavior, which are in stark contrast to rodent models. This study investigates the usage of a porcine model for voluntary binge drinking (BD) and a detailed analysis of gait changes due to motor function deficits during alcohol intoxication.

Methods: Adolescent pigs were trained to drink increasing concentration (0-8%) of alcohol mixed in a 0.2% saccharin solution for 1 h in a two bottle choice test for 2 weeks. The training period was followed by a 3-week alcohol testing period, where animals were given free access to 8% alcohol in 0.2% saccharin solution and 0.2% saccharin water solution. Blood alcohol levels were tested and gait analysis was performed pre-alcohol consumption, last day of training, and Day 5 of each testing period.

Results: Pigs voluntarily consumed alcohol to intoxication at all timepoints with blood alcohol concentration (BAL) ≥80 mg/dl. Spatiotemporal gait parameters including velocity, cadence, cycle time, swing time, stance time, step time, and stride length were perturbed as a result of intoxication. The stratification of the gait data based on BAL revealed that the gait parameters were affected in a dose-dependent manner.

Conclusion: This novel adolescent BD porcine model with inherent anatomical and physiological similarities to humans display similar consumption and intoxication behavior that is likely to yield results that are translatable to human patients.
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http://dx.doi.org/10.1093/alcalc/agaa105DOI Listing
April 2021