Isoflurane Preconditioning Affords Functional Neuroprotection in a Murine Model of Intracerebral Hemorrhage

Gigante, Paul R.; Appelboom, Geoffrey; Hwang, Brian Y.; Haque, Raqeeb; Yeh, Mason L.; Ducruet, Andrew F.; Kellner, Christopher P.; Górski, J; Keesecker, Sarah E.; Connolly, E. Sander

doi:10.1007/978-3-7091-0693-8_23

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…Inhalational anesthetic-induced conditioning with agents such as isoflurane has been reported to produce robust neuroprotection in a variety of acute cerebrovascular conditions including cerebral ischemia, 12 – 14 neonatal hypoxia–ischemia, 43 , 44 and cerebral hemorrhage. 15 , 16 The majority of these studies have focused on characterizing and mechanistically understanding the neural protection afforded by volatile anesthetics – that is, how anesthetics such as isoflurane protect against neuronal cell death, ischemic brain injury, and neurological deficits. Recently, however, Chi and colleagues 45 examined whether the brain protection afforded by isoflurane is, in part, due to vascular protection induced via specific vascular-related molecular cascades.…”

Section: Discussionmentioning

confidence: 99%

“… 11 As a follow-up to this proof-of-concept study, we next turned our attention toward translating this concept to a post-SAH conditioning paradigm. Given the strong experimental evidence that volatile anesthetics when delivered not only as a preconditioning stimulus 12 – 16 but also as a postconditioning therapeutic agent 17 , 18 provide robust protection against acute brain injury, we began our translational studies in SAH by examining the neurovascular protection afforded by isoflurane postconditioning.…”

Section: Introductionmentioning

confidence: 99%

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HIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage

Johnson

Nelson

Harries

et al. 2015

Ann Clin Transl Neurol

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ObjectiveOutcome after aneurysmal subarachnoid hemorrhage (SAH) depends critically on delayed cerebral ischemia (DCI) – a process driven primarily by vascular events including cerebral vasospasm, microvessel thrombosis, and microvascular dysfunction. This study sought to determine the impact of postconditioning – the phenomenon whereby endogenous protection against severe injury is enhanced by subsequent exposure to a mild stressor – on SAH-induced DCI.MethodsAdult male C57BL/6 mice were subjected to sham, SAH, or SAH plus isoflurane postconditioning. Neurological outcome was assessed daily via sensorimotor scoring. Contributors to DCI including cerebral vasospasm, microvessel thrombosis, and microvascular dysfunction were measured 3 days later. Isoflurane-induced changes in hypoxia-inducible factor 1alpha (HIF-1α)-dependent genes were assessed via quantitative polymerase chain reaction. HIF-1α was inhibited pharmacologically via 2-methoxyestradiol (2ME2) or genetically via endothelial cell HIF-1α-null mice (EC-HIF-1α-null). All experiments were performed in a randomized and blinded fashion.ResultsIsoflurane postconditioning initiated at clinically relevant time points after SAH significantly reduced cerebral vasospasm, microvessel thrombosis, microvascular dysfunction, and neurological deficits in wild-type (WT) mice. Isoflurane modulated HIF-1α-dependent genes – changes that were abolished in 2ME2-treated WT mice and EC-HIF-1α-null mice. Isoflurane-induced DCI protection was attenuated in 2ME2-treated WT mice and EC-HIF-1α-null mice.InterpretationIsoflurane postconditioning provides strong HIF-1α-mediated macro- and microvascular protection in SAH, leading to improved neurological outcome. These results implicate cerebral vessels as a key target for the brain protection afforded by isoflurane postconditioning, and HIF-1α as a critical mediator of this vascular protection. They also identify isoflurane postconditioning as a promising novel therapeutic for SAH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage

Johnson

Nelson

Harries

et al. 2015

Ann Clin Transl Neurol

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“…The inhaled anesthetic gases that are widely applied in clinic settings and in experimental studies include isoflurane, sevoflurane and xenon, especially isoflurane (Zhang et al, 2012(Zhang et al, , 2014bHu et al, 2014;Sehba, 2014;Chen et al, 2015a;Cheng et al, 2015;Zuloaga et al, 2015). Importantly, isoflurane has been reported to reduce the brain injury induced by ischemic stroke (Bickler and Fahlman, 2006;Li and Zuo, 2009;Bedirli et al, 2012;Yin et al, 2014;Sosunov et al, 2015) and hemorrhagic stroke (Gigante et al, 2011;Altay et al, 2012). Sevoflurane protects the brain against ischemic stroke (Engelhard et al, 2003;Wang et al, 2011Wang et al, , 2016Yu et al, 2011;Bedirli et al, 2012;Li et al, 2014), and hemorrhagic stroke (Karwacki et al, 2005;Lee et al, 2015).…”

Section: Protective Effect Of Inhaled Anesthetic Gasesmentioning

confidence: 99%

“…The inhaled anesthetic gases can be used as either a pre-conditioning approach or a post-conditioning one. Preconditioning has demonstrated protective effects against TBI (Harris et al, 2013;Deng et al, 2014;Khan et al, 2015;Shu et al, 2016), ischemic stroke (Dingley et al, 2006;Wang et al, 2011Wang et al, , 2016Yu et al, 2011;Liu et al, 2013;Shi et al, 2013), and hemorrhagic stroke (Gigante et al, 2011;Sheng et al, 2012). Post-conditioning is a relative new concept and it has been reported in ischemic stroke (Li et al, 2014;Yin et al, 2014;Lee et al, 2015;Liu et al, 2016).…”

Section: Protective Effect Of Inhaled Anesthetic Gasesmentioning

confidence: 99%

Anti-oxidative aspect of inhaled anesthetic gases against acute brain injury

2016

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Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury.

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“…As well as the plethora of preclinical data on the effects of PC on ischemic brain injury, there is also evidence that some PC stimuli may also protect against intracerebral hemorrhage-induced brain damage (Xi, Hua et al 2000; Qin, Song et al 2007; Gigante, Appelboom et al 2011). However, interestingly, a recent study of remote ischemic post-conditioning found no protective effect against intracerebral hemorrhage (Geng, Ren et al 2012) although that paradigm protects against ischemic brain damage.…”

Section: Pre-clinical Data For Preconditioning: Special Requirements?mentioning

confidence: 99%

Should the STAIR Criteria Be Modified for Preconditioning Studies?

Wang

Keep

2012

Transl. Stroke Res.

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Diverse preconditioning (PC) stimuli protect against a wide variety of neuronal insults in animal models, engendering enthusiasm that PC could be used to protect the brain clinically. Candidate clinical applications include cardiac and vascular surgery, after subarachnoid hemorrhage, and prior to conditions in which acute neuronal injury is anticipated. However, disappointments in clinical validation of multiple neuroprotectants suggest potential problems translating animal data into successful human therapies. Thus, despite strong promise of preclinical PC studies, caution should be maintained in translating these findings into clinical applications. The Stroke Therapy Academic Industry Roundtable (STAIR) working group and the National institute of Neurological Diseases and Stroke (NINDS) proposed working guidelines to improve the utility of preclinical studies that form the foundation of therapies for neurological disease. Here, we review the applicability of these consensus criteria to preconditioning studies and discuss additional considerations for PC studies. We propose that special attention should be paid to several areas, including 1) safety and dosage of PC treatments; 2) meticulously matching preclinical modeling to the human condition to be tested; and 3) timing of both the initiation and discontinuation of the PC stimulus relative to injury ictus.

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Isoflurane Preconditioning Affords Functional Neuroprotection in a Murine Model of Intracerebral Hemorrhage

Abstract: These results demonstrate the early functional neuroprotective effects of anesthetic preconditioning in ICH and suggest that methods of preconditioning that afford protection in ischemia may also provide protection in ICH.

Cited by 12 publications

References 28 publications

HIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage

HIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage

Anti-oxidative aspect of inhaled anesthetic gases against acute brain injury

Should the STAIR Criteria Be Modified for Preconditioning Studies?

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