Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

Seiffge, David J; Lapina, Natalia; Tsagogiorgas, Charalambos; Theisinger, Bastian; Henning, Robert H.; Schilling, Lothar

doi:10.1016/j.expneurol.2012.06.007

Cited by 15 publications

(19 citation statements)

References 44 publications

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“…One 2-hr MCAo study in mice reported no effect of NBO on hypoxic volumes determined ex vivo 135min after IV administration of non-radioactive EF-5 [ 67 ]; a finding not addressed by the authors. In another 2-hr MCAo study performed in Sprague-Dawley rats, NBO administered together with perfluorocarbons early after MCAo resulted in major (2 to 4-fold) reductions in core volume (assessed using Silver staining) but only minor (15–20%) reductions in hypoxia volume, assessed using the ex vivo pimonidazole method 8 or 24hr later [ 68 ]. These earlier findings are entirely consistent with our observations.…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

et al. 2017

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PurposeMapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity.MethodsThirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions.ResultsAs expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2.ConclusionsDespite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

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Section: Discussionmentioning

confidence: 99%

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

et al. 2017

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“…Brain damage was determined using silver nitrate staining of serial coronal slices and corrected for swelling accordingly6732. Hemispheric infarction along the fronto-occipital axis was calculated for 3 regions (frontal, middle and occipital) as area under the curve (AUC; see Supplementary Information).…”

Section: Methodsmentioning

confidence: 99%

“…This method has repeatedly been modified, particularly by using a silicone cover of the filament, and we successfully used it to study the role of early hypoxia in ischemic damage67. The intravascular filament occlusion method is preferred as its removal at any desired time allows superior control of the size of ischemic damage.…”

mentioning

confidence: 99%

“…Currently the most widely used focal brain ischemia model is the intravascular filament occlusion of the middle cerebral artery (MCA) in rodents originally developed in rat 5 . This method has repeatedly been modified, particularly by using a silicone cover of the filament, and we successfully used it to study the role of early hypoxia in ischemic damage 6 7 . The intravascular filament occlusion method is preferred as its removal at any desired time allows superior control of the size of ischemic damage.…”

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confidence: 99%

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Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats

Shanbhag

Henning

Schilling

2016

Sci Rep

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Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients.

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“…Administration of an SFA emulsion in conjunction with NBO is easily afforded in the pre-hospital phase. It may not only provide a significant neuroprotective effects but also expand the time window for ischemic stroke therapy (Seiffge et al, 2012).…”

Section: Nbo Plus Semifluorinated Alkane (Sfa)-containing Emulsion (Amentioning

confidence: 99%

Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

2016

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Up to now, over 1,000 experimental treatments found in cells and rodents have been difficult to translate to human ischemic stroke. Since ischemia and reperfusion, two separate stages of ischemic stroke, have different pathophysiological mechanisms leading to brain injury, a combination of protective agents targeting ischemia and reperfusion respectively may obtain substantially better results than a single agent. Normobaric hyperoxia (NBO) has been shown to exhibit neuro- and vaso-protective effects by improving tissue oxygenation when it is given during ischemia, however the effect of NBO would diminish when the duration of ischemia and reperfusion was extended. Therefore, during reperfusion drug treatment targeting inflammation, oxidative stress and free radical scavenger would be a useful adjuvant to extend the therapeutic window of tissue plasminogen activator, the only United States Food and Drug Administration (FDA) approved treatment for acute ischemic stroke. In this review, we discussed the neuro- and vaso-protective effects of NBO and recent finding of combining NBO with other drugs.

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Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

Cited by 15 publications

References 44 publications

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats

Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

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