Middle Meningeal Artery Embolization with Sustained Release Bevacizumab Hydrogel for Patients with Chronic Subdural Hematoma
Chronic subdural hematoma (cSDH) affects mostly older people, with increasing relevance due to aging of the population and the increasing use of antiplatelets/anticoagulants. cSDH is projected to affect at least 60,000 new individuals annually and surpass brain tumors as the most common cranial surgical condition in the U.S. by 2030. Bevacizumab, an anti-VEGF monoclonal antibody which also has anti-inflammatory effects, has demonstrated efficacy in cSDH cases when either administered intravenously for concurrent diseases such as recurrent glioblastoma or intra-arterially through the middle meningeal artery embolization for cSDH. In a collaboration with Dr. Kevin McHugh PhD at Rice University's Department of Bioengineering, we aim to develop a sustained release bevacizumab hydrogel embolic for embolization treatment of patients with cSDH.
The Role of SuPAR in a Murine Middle Cerebral Artery Occlusion Stroke Model
Stroke is the fifth leading cause of death and the leading cause of adult disability with an estimated cost of near $70 billion in the United States. A stroke is an interruption of the blood supply to any part of the brain, which can lead to brain cell death causing a myriad of symptoms, ranging from extremity weakness to death. Soluble urokinase plasminogen activator receptor (SuPar) is a protein that activates innate immunity on renal and cardiovascular disease, but it's role is poorly understood in disease. It is believed that overexpressing SuPAR will have significantly greater infarct volumes and worse neurological outcomes in strokes; and further complicated by diets high in fat. This project is a collaboration with the lab of Dr. Selim Hayek MD, Professor and Chair of Internal Medicine at UTMB. Our first aim is to perform a preliminary experiment to compare wild type and SuPAR mice who have undergone middle cerebral artery occlusion for 90 minutes with reperfusion. The study will also investigate normal versus high fat diet (HFD) of these two strains, as it is hypothesized that mice on a HFD will experience more of SuPAR's deleterious effects by increasing systemic inflammation and SuPAR expression levels.
Rabbit Model for Gliomas
As proven in our previous NeuroOncology publication, we were able to create a reliable rabbit model for gliomas and therapy via intra-arterial infusion through the internal carotid artery route. While this method is fine for cerebral gliomas situated more anteriorly, how would we get treatment to gliomas located in the midbrain or more posteriorly? With collaboration of Dr. Christopher Young MD, PhD at UTMB/MD Anderson and Dr. Frederick Lang MD, Chair of Neurosurgery at MD Anderson, we hope to develop a rabbit model for gliomas using the basilar artery approach.
As previously published, we will create a rabbit model of human glioma by xenotransplantation of cultured human glioblastoma cells into immunodeficient New Zealand white rabbits. The establishment of tumors in animals by xenografting tumor material, mostly in the form of established cell lines, has been highly valuable in the search for mechanisms that determine tumor formation, growth and progression. The advantages of cell line-based models are 1) good reproducibility with regards to engraftment rate and 2) reliable growth and disease progression. Most often, human cell line-derived xenografts also display some levels of angiogenesis. This method for human glioma modeling in rabbits can provide the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery.
Development of Wireless Neuromodulation in a Sheep Model
In a collaboration with Scott Crosby at NeuroConnect, Dr. Jacob Robinson PhD at Rice Engineering and Drs. Sarah Heilbronner PHD and Nicole Provenza PhD at Baylor College of Medicine, Department of Neurosurgery, we hope to provide an opportunity to develop new wireless neuromodulation therapy that may provide more effective care in patients. Neuromodulation is relatively a new frontier in the medical field and can provide an effective treatment for pain, psychiatric disorders and rehabilitation. By enhancing or suppressing certain stimuli of the nervous system, neuromodulation may provide patients with effective and less invasive means of treating disease. By deploying a wireless magnetoelectric stimulator into the subarachnoid space via lumbar puncture or performing a craniotomy to implant the stimulator between the dura mater and "bone flap", we aim to effectively stimulate various spinal nerves and areas of the brain.
Use of Photobiomodulation in a Murine Model of Middle Cerebral Artery Occlusion
Stroke is the fifth leading cause of death and the leading cause of adult disability with an estimated cost of near $70 billion in the United States. A stroke is an interruption of the blood supply to any part of the brain, which can lead to brain cell death causing a myriad of symptoms, ranging from extremity weakness to death. This study will investigate a new, non-invasive treatment called photobiomodulation, which is a method that uses light therapy to stimulate brain repair and reduce damage after stroke. By exploring this approach, we hope to find a safer, drug-free way to improve stroke recovery and outcomes for future patients in this collaboration with Dr. Ajay Wakhloo MD, PhD of Prometheus Therapeutics.