Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage

Fujiwara, Norio; Mandeville, Emiri T.; Xu, Geng; Luo, Yumin; Arai, Ken; Wang, Xiaoying; Ji, Xunming; Singhal, Aneesh B.; Lo, Eng H.

doi:10.1161/strokeaha.110.593350

Cited by 22 publications

(12 citation statements)

References 16 publications

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“…Furthermore, NBO did not appear to worsen postischemic brain hemorrhage, edema, or blood-brain barrier damage, and it may not increase matrix metalloproteinase levels or various other markers of oxidative stress (Veltkamp, et al, 2006, Liu, et al, 2009). In addition, a recent study demonstrated that NBO did not worsen outcomes in a rat model of intracerebral hemorrhage (ICH), suggesting that treatments could potentially be started even before a definitive diagnosis to distinguish ischemic versus hemorrhagic stroke (Fujiwara, et al, 2011). Based on these preclinical animal studies, NBO treatment was extended to humans in a few early proof-of-concept clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats

Esposito

Mandeville

Hayakawa

et al. 2013

Experimental Neurology

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Normobaric oxygen (NBO) reduces infarction at 24-48 hrs in experimental models of focal cerebral ischemia. However, to be clinically relevant, longer term safety and efficacy must be explored. Here, we assessed the effects of NBO on glial activation, neurovascular recovery, and behavioral outcomes at 2 weeks after transient focal ischemia in rats. 100 min transient focal ischemia was induced by intraluminal occlusion of the middle cerebral artery in adult male Sprague-Dawley rats. Animals were randomized into sham, controls or 85 NBO started 15 minutes after ischemic onset. Infarct volumes and behavioral outcomes were blindly quantified. Immunohistochemistry was used to examine the effects of NBO on glial activation and neurovascular responses. After 2 weeks of reperfusion the infarct volume was marked reduced in animals subjected to NBO. They also had better outcomes in forelimb placement test and in bodyswing test and weight loss reduction. After 14 days, NBO decreased expression of Iba1, a marker of activated microglia, and GFAP, a marker of activated astrocytes. NBO treatment had no detectable effect on angiogenesis. These results suggest that protective effects of NBO may persist for up to 2 weeks post-stroke.

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Section: Introductionmentioning

confidence: 99%

Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats

Esposito

Mandeville

Hayakawa

et al. 2013

Experimental Neurology

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“…Furthermore, ketamine, an N-methyl d-aspartate (NMDA) receptor antagonist, may possibly reduce NMDA receptor-dependant excitotoxicity, and therefore ameliorate outcomes in brain injury models. Volatile anesthetics, such as isoflurane, are alternatively used in preclinical ICH research and hold unique advantages over injectable agents, including the quick alteration of anesthesia depth and short recovery times 19 . The main disadvantage of gas anesthesia is the need of elaborate equipment (vaporizer, flow-meter, mask breathing circuit) as well as the possibility of human gas exposure.…”

Section: Discussionmentioning

confidence: 99%

Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase

Krafft

Rolland

Ďuriš

et al. 2012

JoVE

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Spontaneous intracerebral hemorrhage (ICH) defines a potentially life-threatening neurological malady that accounts for 10-15% of all strokerelated hospitalizations and for which no effective treatments are available to date 1,2 . Because of the heterogeneity of ICH in humans, various preclinical models are needed to thoroughly explore prospective therapeutic strategies Resultant perihematomal edema and neurofunctional deficits can be quantified from both models. In this study, we described and evaluated a modified double injection model of autologous whole blood 6 as well as an ICH injection model of bacterial collagenase 7 , both of which target the basal ganglia (corpus striatum) of male CD-1 mice. We assessed neurofunctional deficits and brain edema at 24 and 72 hr after ICH induction. Intrastriatal injection of autologous blood (30 μl) or bacterial collagenase (0.075U) caused reproducible neurofunctional deficits in mice and significantly increased brain edema at 24 and 72 hr after surgery (p<0.05). In conclusion, both models yield consistent hemorrhagic infarcts and represent basic methods for preclinical ICH research. Video LinkThe video component of this article can be found at

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“…On the contrary, the described phenomenon of hematoma disappearance could be used to improve accuracy of MRI, especially because we (and others) 16 demonstrated that NBO appears safe after ICH ( Figure 6). For instance, we demonstrated here that perihematoma magnetic resonance PWI becomes feasible after a 30-minute preparation period of NBO.…”

Section: Potential Implications For Clinical Practicementioning

confidence: 92%

Intracerebral Hematomas Disappear on T2*-Weighted Images During Normobaric Oxygen Therapy

Gaberel

Gakuba²,

Hébert³

et al. 2013

Stroke

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ICH was induced by intrastriatal collagenase injection in 16 mice. One mouse died during the surgery and was therefore excluded from the analysis. Three behavioral tests were performed before the ICH and at +24 hours to assess the functional deficits induced by the ICH Background and Purpose-The aim of the present study was to investigate the effects of normobaric oxygen (NBO) therapy on T2*-weighted images of intracranial hemorrhages (ICHs). Methods-Two common models of ICH were performed in mice, and longitudinal T2*-weighted images of the hematomas were acquired under normoxia or NBO. The effects of NBO were also investigated on perfusion-weighted imaging, susceptibility-weighted imaging, and molecular imaging of vascular cell adhesion molecule-1 after ICH. Last, we performed neurological testing, including neuroscore, actimetry, and gait analysis (Catwalk), to study the influence of NBO on neurological outcome of mice presenting ICH. Results-Our results demonstrated that NBO, even during a short period of time, dramatically reduces the sensitivity of T2*-weighted imaging to detect ICH. Moreover, we provide evidence that the disappearance of ICH on T2*-weighted imaging could be used to improve accuracy of perfusion-weighted imaging and to allow molecular imaging after ICH. Importantly, a 30-minute NBO preparation 24 hours after ICH onset does not influence neurological outcome. Conclusions-We provide an experimental demonstration that NBO significantly affects T2*-weighted imaging in ICH.Although this phenomenon could lead to inaccurate assessment of ICH volume, it could also be safely used to allow perfusion-weighted imaging and molecular imaging. in mice. The general state of the mice was assessed using a 5-point neuroscore scale (0=no apparent deficit; 1=slight deficit; 2=circling; 3=heavy circling or no movement at all; or 4=death). 4 The spontaneous global locomotor activity was quantified during 10 minutes using an actimeter (Imetronic, Pessac, France) as described previously.5 Briefly, global locomotor activity was quantified using activity cages equipped with horizontal infrared beams located across the long axis of the cage (IMETRONIC, France). Mice were placed in individual acrylic chambers (30×20×20 cm) for 10 minutes. The number of horizontal movements (horizontal crossings) was determined by breaks in movement-sensitive photobeams that were then converted into locomotor activity counts. A gait analysis was also performed using the Catwalk XT system (Noldus Information Technology, Wageningen, The Netherlands). The apparatus consists of an enclosed walkway (130×68×152 cm) on a glass plate that is traversed by the mice from one side to the other. Green light enters at the long edge of the plate and is completely internally reflected. Light is able to escape only at those areas where the animal's paws make contact with the glass plate; as a result, the light is scattered. Real footprints are captured by a high-speed video camera that is positioned underneath the walkway. The video camera transforms...

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Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage

Cited by 22 publications

References 16 publications

Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats

Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats

Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase

Intracerebral Hematomas Disappear on T2*-Weighted Images During Normobaric Oxygen Therapy

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