Search bioRxiv⌕ Search

Biology subjects

Moline, B. C.

Publications and source records attributed to Moline, B. C..

2 recordsLinked to original sources

Aberrant Pain Phenotypes Emerge Following Prenatal Hypoxic-Ischemic Injury in a Rabbit Model of Cerebral Palsy

Cerebral Palsy (CP) is the most common motor disability in childhood, and the most frequent comorbidity is pain. Rabbit kits subjected to prenatal hypoxia-ischemia (HI) exhibit allodynia and an expansion of nociceptive afferents in the lumbar spinal cord at postnatal day (P5). In this study, we examined how HI alters the development of multiple sensory modalities and its effect on psychosocial measures and C-fiber distribution in the spinal cord. To do this, we performed an HI surgery to occlude blood flow to fetal New Zealand White rabbits for 40 minutes, or a sham surgery. We performed von Frey, Hargreaves, and a cold allodynia test at P1, P5, P11, and P18. Additionally, we performed open field, a two-texture preference test, and immunofluorescence assays at P18. HI kits exhibit altered development and allodynia in von Frey and Hargreaves and decreased sensitivity to cold. HI kits spend less time on the aversive side of the two-texture preference apparatus and more time in the center of an open field but a higher ratio of that time immobile. This is accompanied by changes in the distribution of C-fibers in the dorsal horn of the cervical and lumbar spinal cord. A principal components analysis revealed prenatal HI produces coordinated alterations across sensory and behavioral domains and multivariate phenotyping captures the overall HI phenotype more comprehensively than any single measure. Overall, HI rabbits kits exhibit altered sensory development, allodynia, anxiety-like behavior, and changes to the distribution of nociceptive afferents in the dorsal horn of the spinal cord.

neuroscience↗

A novel machine-learning classification model detects oxidative fiber type transitions in a rabbit model of cerebral palsy

The distribution of slow-and fast-twitch fiber types in a skeletal muscle heavily influences its physiology. Muscle biopsy studies indicate atypical fiber type composition and fiber size variation in children with cerebral palsy (CP), but subjects have variable treatment history and a variety of muscles affected, so uncertainties remain. In this study, we developed a novel machine-learning classification model to perform high-throughput fiber typing of complete transverse muscle sections. Our XGBoost algorithm-based prediction model yielded a balanced accuracy score of 0.89 and a macro F1-score of 0.89, reflecting its ability to robustly predict muscle fiber type from myosin heavy chain (MyHC) isoform immunofluorescence intensities and morphological descriptors. This is the first reported fiber type classifier to consider hybrid fibers, which is a major advance, considering at least 20% of myofibers are hybrid yet they are routinely overlooked due to difficulty in their detection. We used this classification model to define fiber types of more than 7 million myofibers from flexor-extensor muscle pairs in rabbits that experienced hypoxia-ischemia (HI) injury in utero (modeling CP), and typically developing sham rabbits. We observed an oxidative fiber type shift in flexor muscles (biceps brachii and tibialis anterior) of HI rabbits at postnatal day (P)14-20 and P30-32 (weaning age). This altered fiber type composition imparts reduced contractile force and is amenable to sustained muscle activity; it may reflect chronic low-frequency motor unit activation. This work supports prior clinical reports that developmental trajectories of muscle fibers are disrupted in CP.

neuroscience↗