Abstract

PurposeThe vasodilatory response to inhaled CO2 occurs in the acute stroke ischemic penumbra and may be a potential therapeutic modality.MethodsTwenty-two Sprague-Dawley rats were subjected to 90-min occlusion of the M2 segment of the middle cerebral artery (M2CAO) by endovascular technique. The animals were administered different C02 concentrations and scanned serially with 9.4 T MRI. Infarct tissue was determined by diffusion-weighted imaging (DWI) and hypoperfused tissue was determined by arterial spin labeling (PWI).Results4 animals were administered room air (RA)+ 6% CO2 (group 1), 6 animals RA+12% CO2 (Group 2) and 4 animals only RA (group 3). In the rats with CO2 administered (groups 1 and 2), the DWI lesion to cerebral hypoperfusion volume ratio (SD) at pre-CO2 administration, was 0.145(0.168), which increased to 0.708(0.731) during CO2 administration and reduced to 0.533(0.527) post-CO2 administration. In 9 of 10 rats the hypoperfused volume decreased when CO2 was administered. When CO2 was stopped the hypoperfused volume became larger again. Administration of RA+12% CO2 (Group 2) decreased the volume of CBF hypoperfusion significantly compared to the control group (95%CI: 0.084 ± 0.0213, p = 0.004).ConclusionInhaled CO2 appears to reduce the size of the hypoperfused tissue volume during acute stroke and may be a potential modality for treatment of acute ischemic stroke. These findings will nonetheless need to be validated in a larger cohort in other centers.

Highlights

  • Stroke is the second most common cause of death worldwide and the major cause of disability [1]

  • The discovery of factors that can affect the perfusion by modulating the leptomeningeal collaterals and sustaining the penumbra will allow more patients to be treated by recanalization therapies

  • Animals in research is regulated by a common law EU framework (Directive 2010/63/ EU) and the experiments were conducted in compliance with the Animal Research: Reporting In-Vivo Experiments (ARRIVE) guidelines

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Summary

Introduction

Stroke is the second most common cause of death worldwide and the major cause of disability [1]. During an acute ischemic stroke, the leptomeningeal collateral circulation keeps the ischemic penumbra in the brain from succumbing to infarction [2]. Studies have shown that in some patients, the ischemic penumbra can last hours or even days before it becomes infarcted [3]. The discovery of factors that can affect the perfusion by modulating the leptomeningeal collaterals and sustaining the penumbra will allow more patients to be treated by recanalization therapies. Carbon dioxide (CO2) is one of the strongest natural vasodilators. Cerebral blood flow (CBF) changes in concordance with changes in the partial pressure of CO2 (PaCO2) within the range of

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