Time-varying caloric vestibular stimulation for the treatment of neurodegenerative disease.

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Time-varying caloric vestibular stimulation (tvCVS) is a new form of non-invasive neuromodulation similar to, but different from, diagnostic caloric vestibular stimulation (CVS). Using a non-invasive, solid-state delivery device, tvCVS has been successfully used in a human clinical trial with Parkinson's disease (PD) subjects. Additionally, the effects of tvCVS on brain activation have been studied in healthy human subjects using transcranial Doppler sonography (TCD) and functional magnetic resonance imaging (BOLD fMRI). A novel finding in the TCD and fMRI studies was the induction of cerebral blood flow velocity (CBFv) oscillations. How such oscillations might lead to the observed clinical effects seen in PD subjects will be discussed. Enabling studies of tvCVS with rodents is an attractive goal in support of explorations of the mechanism of action. Male Wistar rats were used in a proof-of-concept study described herein. Rats were anesthetized (isoflurane) and ventilated for the duration of the tvCVS runs. Time-varying thermal stimuli were administered using a digital temperature controller to modulate Peltier-type heater/cooler devices. Blunt ear bars conveyed the thermal stimulus to the external ear canals of the rats. Different thermal waveform combinations were evaluated for evidence of successful induction of the CVS effect. It was found that bilateral triangular thermal waveforms could induce oscillations in CBFv both during and after the application of tvCVS. These oscillations were similar to, but different from those observed in awake human subjects. The establishment of a viable animal model for the study of tvCVS will augment ongoing clinical investigations of this new form of neuromodulation in patients with neurodegenerative disease.





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Black, Robert D, and Eduardo Chaparro (2022). Time-varying caloric vestibular stimulation for the treatment of neurodegenerative disease. Frontiers in aging neuroscience, 14. p. 1049637. 10.3389/fnagi.2022.1049637 Retrieved from https://hdl.handle.net/10161/26347.

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Eduardo Chaparro

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Dr. Chaparro received his Medical Doctoral degree from Javeriana University in Bogota - Colombia and his Ph.D. in Medical Sciences with a focus on Physiology, Pharmacology, and Neuroscience from the University of South Florida in Tampa - Florida. He joined the Anesthesiology Department at USF for his graduate work to study the effects of anesthetics and anti-apoptotic compounds in brain ischemia. After completing his Ph.D., he came to Duke University for his post-doctoral training at the Multidisciplinary Neuroprotection Laboratory where he dedicated his time to testing drugs and devices in different animal models of neurological conditions getting special recognition for successfully testing the first hepatocyte growth factor mimetic in an animal model of transient cerebral ischemia. He also successfully tested a vestibular stimulator approved by the FDA for human use. After completing his post-doctoral training, Dr. Chaparro joined the Cerebrovascular and Skull Base Division at the Duke University Department of Neurosurgery where he has dedicated his career to testing treatments for neurovascular conditions including stroke, moyamoya disease, aneurysms, intra-cerebral hemorrhages, intravascular stent thrombogenicity, traumatic brain injury, and epilepsy. Dr. Chaparro is also an entrepreneur, and his interest in hypothermia as a treatment for neuronal inflammation, let him patent a brain-cooling device that has been successfully tested in non-human primates. He assembles a team of engineers, neuroscientists, and business experts to create Neurocool, a startup to develop the prototype further. As a CEO he is working on getting FDA approval and developing a human-compatible device aiming to help patients with central nervous system inflammatory conditions.

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