Isoflurane Prevents Delayed Cell Death in an Organotypic Slice Culture Model of Cerebral Ischemia

Sullivan, Breandan; Leu, David; Taylor, Donald M.; Fahlman, Christian S.; Bickler, Philip E.

doi:10.1097/00000542-200201000-00033

Cited by 68 publications

(42 citation statements)

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“…Twenty-four hours before insult, the cultured slices were exposed to 75% xenon, 20% oxygen, and 5% carbon dioxide (or 75% nitrogen for the control group) for 45 mins at 371C (n ¼ 5 to 9/group). OGD was induced in a balanced salt solution for 2 h. Images were obtained before and 3 days after OGD to quantify dead cells with propidium iodide (PI) fluorescence; the intensity of PI fluorescence after OGD (reflective of the number of dead cells) (Sullivan et al, 2002), less the fluorescence at baseline, reflected the neuroprotective benefit derived from preconditioning. Propidium iodide intensity, corresponding to the number of dead neurons, was assessed in CA1 and dentate gyrus areas of the hippocampus by one author who was masked to the treatment groups.…”

Section: Hippocampal Slice Culturementioning

confidence: 99%

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Hossain

Pettet

et al. 2006

J Cereb Blood Flow Metab

165

111

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Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3 0 ,5 0 -monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.

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Section: Hippocampal Slice Culturementioning

confidence: 99%

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Hossain

Pettet

et al. 2006

J Cereb Blood Flow Metab

165

111

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“…As a component of our MCAO animal protocol, we used the inhalational anesthetic isoflurane for induction and maintenance of anesthesia during the ischemic period alone. We recognize that isoflurane, like other anesthetics, has been shown previously to confer protection from cerebral ischemia-reperfusion injury when delivered before ischemia (Kapinya et al, 2002;Sullivan et al, 2002). However, isoflurane was used for anesthesia in both control-treated and ␦V1-1-treated animals during the ischemic period.…”

Section: Delayed Delivery Of ␦V1-1-tat During Reperfusion Confers Promentioning

confidence: 99%

Protein Kinase C δ Mediates Cerebral Reperfusion InjuryIn Vivo

Bright¹,

Raval²,

Dembner³

et al. 2004

J. Neurosci.

185

171

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Protein kinase C (PKC) has been implicated in mediating ischemic and reperfusion damage in multiple organs. However, conflicting reports exist on the role of individual PKC isozymes in cerebral ischemic injury. Using a peptide inhibitor selective for ␦PKC, ␦V1-1, we found that ␦PKC inhibition reduced cellular injury in a rat hippocampal slice model of cerebral ischemia [oxygen-glucose deprivation (OGD)] when present both during OGD and for the first 3 hr of reperfusion. We next demonstrated peptide delivery to the brain parenchyma after in vivo delivery by detecting biotin-conjugated ␦V1-1 and by measuring inhibition of intracellular ␦PKC translocation, an indicator of ␦PKC activity. Delivery of ␦V1-1 decreased infarct size in an in vivo rat stroke model of transient middle cerebral artery occlusion. Importantly, ␦V1-1 had no effect when delivered immediately before ischemia. However, delivery at the onset, at 1 hr, or at 6 hr of reperfusion reduced injury by 68, 47, and 58%, respectively. Previous work has implicated ␦PKC in mediating apoptotic processes. We therefore determined whether ␦PKC inhibition altered apoptotic cell death or cell survival pathways in our models. We found that ␦V1-1 reduced numbers of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells, indicating decreased apoptosis, increased levels of phospho-Akt, a kinase involved in cell survival pathways, and inhibited BAD (Bcl-2-associated death protein) protein translocation from the cell cytosol to the membrane, indicating inhibition of proapoptotic signaling. These data support a deleterious role for ␦PKC during reperfusion and suggest that ␦V1-1 delivery, even hours after commencement of reperfusion, may provide a therapeutic advantage after cerebral ischemia.

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“…Research in this field may ultimately have an impact on anesthesia practice for patients with a risk of stroke. Accumulative evidence has suggested that volatile anesthetics exert neuroprotective effect when given before and after ischemia [1][2][3][4][5][6][7] . This neuroprotection is believed to occur through complex signal transduction pathways involving the activations of adenosine receptors [8,9] , protein kinase C [10][11][12][13] and mitochondrial adenosine triphosphate-regulated potassium (K ATP ) channels [2,14] .…”

Section: Introductionmentioning

confidence: 99%

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase

et al. 2010

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Abstract:Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia-reperfusion (IR) injury, but the underlying mechanisms have not been fully elucidated. Besides, different protocols would usually lead to different results. The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation (OGD) injury in vitro. Methods Rat hippocampal slices under normoxic conditions (95% O 2 /5% CO 2 ) were pre-exposed to sevoflurane 1, 2 and 3 minimum alveolar concentration (MAC) for 30 min, once or twice, with 15-min washout after each exposure. The slices were then subjected to 13-min OGD treatment (95% N 2 /5% CO 2 , glucose-free), followed by 30-min reoxygenation. The population spikes (PSs) were recorded in the CA1 region of rat hippocampus. The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated, since it could indicate the recovery degree of neuronal function. In addition, to assess the role of mitogen-activated protein kinases (MAPKs) in preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK), and SB203580, an inhibitor of p38 MAPK, were separately added 10 min before sevoflurane exposure. Results Preconditioning once with sevoflurane 1, 2, and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment, from (15.13±3.79)% (control) to (31.88±5.36)%, (44.00±5.01)%, and (49.50±6.25)%, respectively, and twice preconditioning with sevoflurane 1, 2, and 3 MAC increased the percentage to (38.53±4.36)%, (50.74±7.05)% and (55.86±6.23)%, respectively. The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126 [(16.23±4.62)%]. Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro, and preconditioning twice enhances this effect. Besides, the activation of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK) may be involved in this process.

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Isoflurane Prevents Delayed Cell Death in an Organotypic Slice Culture Model of Cerebral Ischemia

Abstract: In an in vitro model of simulated ischemia, 1% isoflurane is of similar potency to 10 microm MK-801 in preventing delayed cell death. Modulation of glutamate excitotoxicity may contribute to the protective mechanism.

Cited by 68 publications

References 0 publications

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Protein Kinase C δ Mediates Cerebral Reperfusion InjuryIn Vivo

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase

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