A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent S
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ORIGINAL ARTICLE
A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent Stroke Models Yi Wang 1,2,3 & Jae H. Choi 4 & Mohammed A. Almekhlafi 5 & Ulf Ziemann 1,2 & Sven Poli 1,2 Received: 20 May 2020 / Revised: 12 August 2020 / Accepted: 3 September 2020 # The Author(s) 2020
Abstract Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat’s total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intraischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions. Keywords Hypothermia . Selective brain cooling . Intra-arterial cold infusion . Ischemic stroke . Rodent model . Endovascular thrombectomy
Introduction Despite strong pre-clinical results indicating the potential of therapeutic hypothermia to protect the brain in acute ischemic * Sven Poli [email protected] 1
Department of Neurology & Stroke, Eberhard-Karls University of Tübingen, Tübingen, Germany
2
Hertie-Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Tübingen, Germany
3
Graduate Training Center of Neuroscience, Eberhard-Karls University of Tübingen, Tübingen, Germany
4
Neurological Surgery PC, Lake Success, NY, USA
5
Department of Clinical Neurosciences and Radiology, Calgary Stroke Program, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
stroke [1, 2], clinical trials so far have failed to show a beneficial effect. Recent randomized controlled tr
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