Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.

Abstract

Background

Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval.

Methods

Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured.

Results

Cerebral infarct sizes (mean±SD) for 0, 15, 30, and 45% Xe were 212±27, 176±55, 160±32, and 198±54 mm, respectively (P=0.023). Neurologic scores (median±interquartile range) followed a similar pattern (P=0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures.

Conclusion

Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1097/aln.0b013e3182746b81

Publication Info

Sheng, Siyuan P, Beilei Lei, Michael L James, Christopher D Lascola, Talaignair N Venkatraman, Jin Yong Jung, Mervyn Maze, Nicholas P Franks, et al. (2012). Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology, 117(6). pp. 1262–1275. 10.1097/aln.0b013e3182746b81 Retrieved from https://hdl.handle.net/10161/23286.

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Scholars@Duke

James

Michael Lucas James

Professor of Anesthesiology

With a clinical background in neuroanesthesia and neurointensive care, I have a special interest in translational research in intracerebral hemorrhage and traumatic brain injury. I am fortunate to be part of a unique team of highly motivated and productive individuals who allow me to propel ideas from bench to bedside and the ability to reverse translate ideas from the bedside back to the bench.

Lascola

Christopher David Lascola

Associate Professor of Radiology

Robert D. Pearlstein

Assistant Professor Emeritus in Neurosurgery
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 antioxidant in treating cerebral ischemia and the other is to examine the efficacy of post-conditioning on outcome of subarachnoid hemorrhage induced cognitive dysfunction.


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