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Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)
Authors:Simone Beretta  Alessandro Versace  Gianfranco Fiore  Marco Piola  Beatrice Martini  Vittorio Bigiogera  Lorenzo Coppadoro  Jacopo Mariani  Lorenzo Tinti  Silvia Pirovano  Laura Monza  Davide Carone  Matteo Riva  Giada Padovano  Gilda Galbiati  Francesco Santangelo  Marco Rasponi  Francesco Padelli  Isabella Giachetti  Domenico Aquino  Susanna Diamanti  Laura Librizzi  Maria Grazia Bruzzone  Marco De Curtis  Carlo Giussani  Erik P. Sganzerla  Carlo Ferrarese
Abstract:Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01302-y.
Keywords:Hypothermia   Device   Cerebrospinal fluid   Vasospasm   Cerebral ischemia   Neuroprotection
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