Cardiovascular effects of mannitol infusion - a comparison study performed on mouse and human

摘要

Monitoring blood-brain barrier (BBB) opening is of great interest in terms of brain drug delivery in the treatment of brain lymphoma and maybe in the future in other diseases like dementia. A method involving BBB disruption (BBBD) by mannitol infusion has been developed in University of Portland, USA, and then exploited in Oulu University Hospital in treatment of primary CSN lymphoma. Proper opening of the BBB is crucial for the treatment, yet there are no methods available for its real-time clinical monitoring. Recently, we presented a combined method using direct-current electroencephalography (DC-EEG) and near-infrared spectroscopy (NIRS) for monitoring BBBD in human. Carotid artery mannitol infusion generated a strongly lateralized DC-EEG response and in NIRS a prolonged increase in the oxy/deoxyhemoglobin ratio. This study explores further BBBD, by focusing on monitoring its cardiovascular effects, when measured in human and mouse. For this, we used photoplethysmography (PPG) and opto-electro-mechanical sensors to gather the signals in human and mouse. Mannitol infusion in human causes strong fluctuations in blood pressure, heart rate and PPG signals, and here we discuss how the acquired signals in mouse model compares to human data. In addition, we present our scale-free monitoring concept that enables monitoring physiological signals similarly when performing experiments in mouse and human neuroimaging setups. By combining microscopic and macroscopic imaging in mouse setup enables us to study correlations between mechanistic cellular data and clinical functional data. Further, this allows us to validate and optimize macroscopic sensing and imaging techniques aimed to be used in human imaging.