Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome.

Abstract

Objectives

We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days.

Design

Controlled, randomized, double-blinded laboratory study.

Setting

Animal research laboratories.

Subjects

Adult Wistar male rats (n = 110).

Interventions

Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed.

Measurements and main results

After argon inhalation for 24 hours immediately following "severe permanent ischemia" induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed.

Conclusions

Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1097/ccm.0000000000003809

Publication Info

Ma, Shuang, Dongmei Chu, Litao Li, Jennifer A Creed, Yu-Mi Ryang, Huaxin Sheng, Wei Yang, David S Warner, et al. (2019). Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome. Critical care medicine, 47(8). pp. e693–e699. 10.1097/ccm.0000000000003809 Retrieved from https://hdl.handle.net/10161/23244.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Sheng

Huaxin Sheng

Associate Professor in Anesthesiology

We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia, and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidants in treating cerebral ischemia, and the other is to investigate the effectiveness of post-conditioning on the outcome of subarachnoid hemorrhage-induced cognitive dysfunction.

We are a part of the NIH Stroke Preclinical Assessment Network (SPAN).

Yang

Wei Yang

Professor in Anesthesiology
Turner

Dennis Alan Turner

Professor of Neurosurgery

Current clinical research interests include clinical trials regarding adaptive or closed-loop deep brain stimulation with novel devices, cellular, and gene therapy in Parkinson disease. Additional trials have included gene therapy for Alzheimer's disease and sensory restoration for development of brain machine interfaces. Clinical treatments include deep brain stimulation, which is now a common procedure for treating Parkinson disease and tremor. Translational approaches include testing new devices and stimulation patterns in the operating room. Pre-clinical research interests focus on evaluation of cerebral perfusion and metabolism changes with stroke, aging and Alzheimer's disease, using both in vivo and in vitro approaches. These basic science interests include new approaches to cerebral blood flow enhancement with brain stimulation, optical imaging of the brain, cellular understanding of metabolism using direct substrate recordings (ie, oxygen, glucose, lactate, respirometry) and developing new methods to understand neurovascular coupling, analyzing complex interactions between neurons, astrocytes and blood vessels.  Further interests include changes in cerebral blood flow with stroke and enhanced recovery after stroke.


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