Distinctive effect of anesthetics on the effect of limb remote ischemic postconditioning following ischemic stroke

Gangling Chen,Abdullah Shafique Ahmad,Sylvain Doré,Pradip Kumar Kamat,Ken Arai

doi:10.1371/journal.pone.0227624

Gangling Chen, Abdullah Shafique Ahmad + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0227624

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Journal: PloS one	Publication Date: Jan 16, 2020
Citations: 15	License type: CC BY 4.0

Affiliation: University of Florida, China Pharmaceutical University

Abstract

Limb remote ischemic postconditioning (LRIP) has been reported as an effective method to reduce the induced experimental stroke damage after ischemic reperfusion (IR) injury. Studies suggest that anesthetics used during induction of ischemic stroke can reduce IR injury, which could affect the actual mechanisms of neuroprotection by LRIP. This study focuses on the comparative effects of anesthetics such as isoflurane and ketamine-xylazine on ischemic injury when used during LRIP. Adult C57BL/6 mice were anesthetized by isoflurane or halothane, and transient middle cerebral artery occlusion (MCAO) was induced through insertion of the filament. Under isoflurane or ketamine-xylazine anesthesia, LRIP was performed after 90 min of reperfusion by carrying out three cycles of 5 min ischemia/5 min reperfusion of the bilateral hind limbs for one session per day for a total of 3 days. Results showed that the use of different anesthetics—isoflurane or ketamine-xylazine—during LRIP had no effects on body weight. However, LRIP was able to improve neurological function as observed by the neurological deficit score in ischemic mice. Interestingly, the neurological deficit in the group where ketamine-xylazine was used was better than the group where isoflurane was used during LRIP. Furthermore, the LRIP was able to prolong the period of the ischemic mice on the rotarod and this effect was more significant in the groups where ketamine-xylazine was used during LRIP. Moreover, LRIP significantly attenuated the infarction volume; however, this effect was independent of the anesthetic used during LRIP. From these results, we conclude that ischemic mice that were subjected to LRIP under ketamine-xylazine anesthesia had better neurological deficit outcomes after stroke.

Highlights

Cerebral ischemia, the most common acute cerebrovascular disease, has been recognized as one of the leading causes of mortality and disability in the world
After middle cerebral artery occlusion (MCAO), the body weights of mice from each experimental group decreased from day 1 to day 3; no significant difference was observed between the groups
As some commonly used anesthetics are used during limb remote ischemic postconditioning (LRIP), we wanted to investigate whether these anesthetics have any adverse or confounding effects along with LRIP on stroke outcomes

Summary

Introduction

The most common acute cerebrovascular disease, has been recognized as one of the leading causes of mortality and disability in the world. Some of the common anesthetics used during MCAO include chloral hydrate, isoflurane, sevoflurane, ketamine, and ketamine-xylazine [3,4,5]. These anesthetics have been documented to have some anti-inflammatory [6,7] and anti-apoptotic properties [8], which may protect the brain from stroke pathology. Ketamine is reported to reduce brain injury by inhibiting apoptosis [11] and to attenuate IR in a chronic post-ischemic pain model of ischemia [7] and myocardial IR [6] through its anti-inflammatory effects. Other anesthetics used alone or in combination, such as sevoflurane and ketamine-xylazine, have been proved to reduce injury in hepatic IR [13], cardiac IR [14], and brain IR [15]

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