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Isoflurane provides long-term protection against focal cerebral ischemia in the rat
Hiroaki Sakai1, Huaxin Sheng, Robert B Yates
1Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Background:
Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection.
Methods:
Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later.
Results:
In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion.
Conclusions:
Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.
Insights
Isoflurane provides lasting neuroprotection against stroke, significantly reducing brain damage and improving neurological function in rats long after the initial injury. This effect is independent of various experimental factors.
Area of Science:
- Anesthesiology
- Neuroscience
- Cerebrovascular Research
Background:
- The long-term neuroprotective effects of isoflurane, a common anesthetic, remain debated.
- This study investigates factors influencing enduring neuroprotection by isoflurane in experimental stroke models.
Purpose of the Study:
- To determine if isoflurane confers long-term neuroprotection against focal cerebral ischemia.
- To examine the influence of ischemia duration, blood pressure, and specific pharmacological agents on isoflurane's neuroprotective effects.
Main Methods:
- Rats underwent middle cerebral artery occlusion (MCAO) under anesthesia or while awake, with varying occlusion durations.
- Neurologic deficits and infarct volumes were assessed at 2 and 8 weeks post-MCAO.
- The impact of phenylephrine and 5-hydroxydecanoate was evaluated, alongside variations in carotid artery occlusion.
Main Results:
- Isoflurane significantly reduced neurologic deficits and infarct volumes compared to awake controls, irrespective of occlusion duration (50 or 80 min).
- Neuroprotection by isoflurane persisted up to 8 weeks post-ischemia.
- Neither phenylephrine nor 5-hydroxydecanoate altered isoflurane's protective effects; permanent carotid ligation exacerbated infarct size.
Conclusions:
- Isoflurane demonstrates consistent, long-term neuroprotection against focal cerebral ischemia.
- This protective effect is independent of ischemia duration, perfusion pressure, and pretreatment with 5-hydroxydecanoate.
