Francesco Mangano, DO, and June Goto, PhD
The Mangano 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 journal, Development
, published the studies findings. The study identified that the gene mutation affects the motility of ependymal cilia, which results in retardation of cerebrospinal fluid (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 study shows different water anisotropic values in the mutant, which is similar to the previous study in human hydrocephalus cases. Presentation of these findings occurred at the American Association of Neurological Surgeons Pediatric section in Houston, University of Cincinnati Neurosurgery Grand Rounds, the National Institutes of Health Hydrocephalus Workshop in Baltimore, Stony Brook University, and University of Kentucky. One of our neurosurgery residents and a current undergraduate University of Cincinnati student working in our laboratory respectively won the Hydrocephalus Research Resident Award and the prestigious Goldwater Scholarship.
Sudakar 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.
Karin Bierbrauer, MD
Dr. Karin Bierbrauer, MD, and Dr. Fracesco Mangano, DO, FACS, FAAP, FACOS, as site principal investigators, 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 is also 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, neurosurgery and the Cincinnati Fetal Center studying the relationship between fetal imaging and outcomes in patients prenatally diagnosed with central nervous system disorders.
Jesse Skoch, MD
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, Dr. Jesse Skoch, MD, monitors cell populations spatiotemporally for calcium channel changes that indicate 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 human patients.
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 clinical, pathological, and radiographic data from four institutions systematically to determine which patients may best benefit from a radical hemispherotomy surgery.
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.
Bone growth after reconstructive skull surgery: Outcomes from patients that have received a bone growth promoting medication are being compared to patients that have had reconstructive skull surgery without this adjunct to better determine how effective the addition of medical therapy is and in which patients it may be most beneficial.
Steven Crone, PhD
The Crone lab
is investigating how neurodegenerative disease and spinal cord injury alter respiratory circuits in an effort to improve breathing and motor function. The Crone lab developed a novel physiological system to measure how often the use of different respiratory muscles for breathing are in use when the diaphragm is not functioning properly in mouse models of amyotrophic lateral sclerosis (ALS). Further, they identified a class of neuron in the spinal cord and brainstem (the V2a class) that degenerates in ALS model mice prior to an abrupt decline in respiratory function. Altering the activity of V2a neurons activates these muscles and improve ventilation. In addition, the Crone lab recently discovered that enhancing the function of V2a neurons can restore function to a previously paralyzed diaphragm following spinal cord injury. The Crone lab is currently investigating the mechanism by which V2a neurons can restore function following injury as well as identifying drug targets in V2a neurons that could improve breathing. In addition, the Crone lab is assessing the potential of transplanting V2a-like neurons derived from human induced pluripotent stem cells to restore respiratory function following spinal cord injury. The results of these studies may help improve breathing in patients with neuromuscular disorders such as spinal muscular atrophy (SMA), muscular dystrophy, ALS, and multiple sclerosis, as well as patients with spinal cord injury or stroke.