Francesco Mangano, DO, and June Goto, PhD

The Mangano/Gotto lab conducted genetic and functional analysis of ependymal cell development to get insight into the pathogenesis of congenital hydrocephalus. The lab identified a new gene mutation causing severe hydrocephalus in early postnatal stage in rodents, and created both mouse and rat models representing similar hydrocephalus development to human congenital hydrocephalus. The group identified that the gene mutation affects motility of ependymal cilia, which results in retardation of CSF in the cerebral ventricles. The group also developed a new rat model of X-linked hydrocephalus, and performed diffusion tensor imaging focusing on the periventricular white matter tracts. The pilot data showed different water anisotropic values in the mutant, which is similar to the previous study in human hydrocephalus cases. Presented these findings at the Society for Research into Hydrocephalus and Spina Bifda (St. Louis, MO). One manuscript is currently under review.

Karin Bierbrauer, MD

Dr. Karin Bierbrauer, MD, and Dr. Fracesco Mangano, DO, FACS, FAAP, FACOS, as site PIs, along with the other faculty, continue their involvement in furthering the study of pediatric patients with Chiari I malformations by participation in the national multi-site Park Reeves Registry. Cincinnati Children's Hospital Medical Center has also recently become one of the centers that is participating in a prospective trial looking at optimizing neurosurgical intervention to improve outcomes for this condition.

Dr. Bierbrauer continues her ongoing collaboration with colleagues in neuroradiology and the Cincinnati Fetal Center coauthoring publications focusing on fetal imaging and outcomes in patients prenatally diagnosed with spinal dysraphism.

Sudhakar Vadivelu, DO

The Vadivelu laboratory conducts translational studies to better understand the complexity of the neurovascular niche as it related to neural development and stroke. One emphasis is to evaluate neurovascular signaling in the development of the cerebral vasculature and its effects on neural cell injury, birth, and regeneration. As an example from bedside to bench, the lab is currently studying cerebrovascular patterning and cerebral reserve in transgenic Notch ligand signaling in mice while in parallel conducting multicenter evaluation of progressive stroke disease in patients with various developmental syndromes including Alagille syndrome. The lab's focus is the neurovascular relationship within the brain, and spinal cord, that predetermines particular patients as having a higher predilection towards cerebral stroke, while also discovering strategies towards not only recovery, but regeneration.

Concurrently, the researchers are studying the role of neurostimulation strategies as it relates to systemic inflammation and stroke. To accomplish lab goals, researchers use models incorporating transgenic mice, small and large animal neuroimaging, and cadaveric studies specifically to understand white matter pathways and its relationship to human vascular development.

Their is a relation between the goals of these translational studies and developing innovative therapeutics for cerebrovascular disorders in children.

Jesse Skoch, MD

Epilepsy:
Live Brain Imaging—
Researchers in the division have been utilizing transgenic mice with cortical neurons that express jellyfish protein that fluoresce dependent on intracellular calcium influx. Using high speed confocal or multiphoton microscopy, researcher monitor cell populations spatiotemporally for calcium channel changes that are indicative of neuronal firing. Researchers modified a high speed microscope to allow imaging of these neurons during seizures, and are comparing this data to simultaneously acquired reflected light imaging. By learning how the reflected light images relate to the fluorescent images, the team hopes to then apply the reflected light imaging to detect seizures in normal, wild-type brains.

Multi-center review of Rasmussen’s encephalitis data—
In order to better understand the significance of MRI and pathologic features of Rasmussen’s encephalitis, an aggressive inflammatory brain disease, researchers are analyzing data from three institutions systematically to determine which patients may best benefit from a radical hemispherotomy surgery.

Craniofacial:
Coagulation labs and transfusion—
A systematic review of outcome data for patients undergoing minimal access surgery for craniosynostosis is underway with a focus on the relevance of pre-operative coagulopathy labs. Researchers hope to determine key factors which may predict a need for blood transfusion, and therefore potential targeted interventions to minimize bleeding.

Steven Crone, PhD

The Crone lab is investigating how amyotrophic lateral sclerosis (ALS) alter respiratory circuits in an effort to improve breathing and motor function in this deadly neurodegenerative disease. The Crone lab developed a novel physiological system to determine how often the use of the accessory respiratory muscles are for breathing in mouse models of disease, an important indicator that the diaphragm is not functioning properly (Journal of Visualized Experiments). Further, they identified a class of neuron in the spinal cord (the V2a class) and brainstem that is able to activate these muscles and improve ventilation, and determined that this class of neuron degenerates in ALS model mice prior to an abrupt decline in respiratory function (Experimental Neurology). The Crone lab is currently investigating whether breathing and survival of ALS model mice can improve by preventing degeneration of V2a neurons, improving the function of surviving V2a neurons, or replacing degenerated V2a neurons with healthy embryonic or stem-cell derived neurons. Using the results of these studies may help improve breathing in patients with neuromuscular disorders such as ALS, spinal muscular atrophy (SMA), muscular dystrophy, and multiple sclerosis, or in patients with spinal cord injury.