Tiss, A. | Search bioRxiv

bioRxiv2024

Imaging demyelinated axons after spinal cord injuries with PET tracer 3F4AP

Spinal cord injuries (SCI) often lead to lifelong disability. Among the various types of injuries, incomplete and discomplete injuries, where some axons remain intact, offer potential for recovery. However, demyelination of these spared axons can worsen disability. Demyelination is a reversible phenomenon, and drugs like 4-aminopyridine (4AP), which target K+ channels in demyelinated axons, show that conduction can be restored. Yet, accurately assessing and monitoring demyelination post-SCI remains challenging due to the lack of suitable imaging methods. In this study, we introduce a novel approach utilizing the positron emission tomography (PET) tracer, [18F]3F4AP, specifically targeting K+ channels in demyelinated axons for SCI imaging. Rats with incomplete contusion injuries were imaged up to one month post-injury, revealing [18F]3F4APs exceptional sensitivity to injury and its ability to detect temporal changes. Further validation through autoradiography and immunohistochemistry confirmed [18F]3F4APs targeting of demyelinated axons. In a proof-of-concept study involving human subjects, [18F]3F4AP differentiated between a severe and a largely recovered incomplete injury, indicating axonal loss and demyelination, respectively. Moreover, alterations in tracer delivery were evident on dynamic PET images, suggestive of differences in spinal cord blood flow between the injuries. In conclusion, [18F]3F4AP demonstrates efficacy in detecting incomplete SCI in both animal models and humans. The potential for monitoring post-SCI demyelination changes and response to therapy underscores the utility of [18F]3F4AP in advancing our understanding and management of spinal cord injuries.

neuroscience↗

bioRxiv2017

Application of High-Dimensional Statistics and Network based Visualization techniques on Arab Diabetes and Obesity data

BackgroundObesity and its co-morbidities are characterized by a chronic low-grade inflammatory state, uncontrolled expression of metabolic measurements and dis-regulation of various forms of stress response. However, the contribution and correlation of inflammation, metabolism and stress responses to the disease are not fully elucidated. In this paper a cross-sectional case study was conducted on clinical data comprising 117 human male and female subjects with and without type 2 diabetes (T2D). Characteristics such as anthropometric, clinical and bio-chemical measurements were collected.\n\nMethodsAssociation of these variables with T2D and BMI were assessed using penalized hierarchical linear and logistic regression. In particular, elastic net, hdi and glinternet were used as regularization models to distinguish between cases and controls. Differential network analysis using closed-form approach was performed to identify pairwise-interaction of variables that influence prediction of the phenotype.\n\nResultsFor the 117 participants, physical variables such as PBF, HDL and TBW had absolute coefficients 0.75, 0.65 and 0.34 using the glinternet approach, biochemical variables such as MIP, ROS and RANTES were identified as determinants of obesity with some interaction between inflammatory markers such as IL4, IL-6, MIP, CSF, Eotaxin and ROS. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) which are considered as an index of endogenous lipid peroxidation and an increase in two inflammatory markers, MIP-1 and RANTES. Furthermore, we obtained 13 pairwise effects. The pairwise effects include pairs from and within physical, clinical and biochemical features, in particular metabolic, inflammatory, and oxidative stress markers.\n\nConclusionsWe showcase that markers of oxidative stress (derived from lipid peroxidation) such as MIP-1 and RANTES participate in the pathogenesis of diseases such as diabetes and obesity in the Arab population.

bioinformatics↗