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Abstract

Project Summary: The overall goal of this study is to gain a better understanding of Syndrome of the Trephined (SoT). SoT is a disorder in which patients who had a segment of their skull removed experience worsening brain function. One of the defining features of SoT is improvement in brain function after the skull is repaired. The goal of this proposal is to create a model of this disease in mice. We also hope to gain a better understanding of the healing process which occurs after a portion of skull has been removed and then replaced. These goals will be accomplished via the following specific aims. Aim 1a is to determine whether worsening brain function can be seen in mice after removing a portion of their skull. Removing a part of the skull is a procedure known as a craniectomy. In aim 1a, all mice will undergo a craniectomy. Following the craniectomy, some mice will have the removed portion of their skull replaced immediately, and some will not have it replaced. After each mouse has undergone surgery, they will be tested to assess brain function using standard behavioral studies. We hypothesize that mice who had their skull replaced will exhibit better brain function compared to those with a skull defect. Aim 1b is to determine whether brain function improves after the previously removed portion of skull has been replaced. Replacement of a previously removed portion of the skull is a procedure known as a cranioplasty. In aim 1b, all mice will again undergo a craniectomy. After the craniectomy mice will again undergo testing to assess brain function. After a period of several weeks, some mice will undergo a cranioplasty and some will not. Brain function will then be assessed again for all mice. We hypothesize that mice who have undergone cranioplasty will show signs of improved brain function compared to those who did not undergo cranioplasty. Aim 2 is to evaluate the healing process which occurs after a portion of the skull has been removed and subsequently replaced. This will be accomplished by euthanizing all mice used in aim 1a and 1b and harvesting their skulls. The skulls will then be stained to highlight different cellular components related to healing. After staining, the skulls will be imaged under a microscope and analyzed. We hypothesize that histological analysis will show a microscopic view of the healing process that occurs after a portion of the skull has been removed and then replaced.

Impact Statement: Little is known about Syndrome of the Trephined (SoT), a devastating neurological condition that occurs in patients who have had a portion of their skull removed to treat brain swelling in strokes or traumatic brain injury. Plastic surgeons working to reconstruct the skull are often faced with patients who develop this poorly understood disorder. Creating a model of SoT will provide a necessary foundation for future research aimed at treating and preventing this condition. The healing process which occurs after a portion of the skull has been replaced in a cranioplasty procedure is also poorly understood. A better understanding of this healing process may lead to the development of novel strategies to improve healing (and thus improve patient outcomes) in this patient population.

Biography
Kerry-Ann Mitchell, MD, PhD, FACS is a surgeon-scientist holding the position of Tenure-Track Assistant Professor within the Department of Plastic & Reconstructive Surgery at The Ohio State University. She is also Director of the Neuroplastic Surgery Program, and the Neuroplastic Surgery Research Laboratory. Her work primarily focuses on complex scalp reconstruction, cranioplasty and patient-specific custom skull implants for adult patients undergoing neurosurgical procedures. Dr. Mitchell earned her undergraduate degree at Benedict College, where she received the Board of Trustees Academic Scholar Award and graduated Summa Cum Laude. Subsequently, she successfully completed her PhD in Neuroscience at the University of Utah, and her Medical Degree at Stanford University School of Medicine. She then completed integrated Plastic and Reconstructive Surgery residency at the University of Southern California. Following residency, she embarked on a distinctive fellowship in Neuroplastic and Reconstructive Surgery at Johns Hopkins University. This prestigious fellowship provided her with exceptional opportunities to excel in neuro-cranial reconstruction, conduct groundbreaking research in cranial implant and reconstruction, and contribute to improving outcomes for patient with complex scalp and skull deformities worldwide seeking specialized care. She is Board Certified by the American Board of Plastic Surgery, and a Fellow of the American College of Surgeons.