Resistance of the sheep skull after a monocortical cranial graft harvest

Laure, B.; Petraud, A.; Sury, F.; Tranquart, F.; Goga, D.

doi:10.1016/j.jcms.2011.03.013

Cited by 10 publications

(8 citation statements)

References 21 publications

(19 reference statements)

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“…Here, we established sheep (a species previously treated with ultrasound to induce thermal lesions 32 ) as an experimental system for obicodilation, our rationale being that their skull is close to that of humans in regards to thickness, porosity and the curvature of the calvarium 32 ( Figure 1 ). This similarity also extends to the morphology of the brain, which, although smaller than that of humans, is also non-homogenous and gyrencephalic 33 . Finally, sheep can also live for at least 10 years and develop an AD-like pathology with age, further underscoring the attractiveness of this model for dementia research 34 .…”

Section: Introductionmentioning

confidence: 57%

“…In the first instance, we aimed to use the HIFU transducer with a relatively large focus in order to treat larger areas of the brain, which is particularly important for diseases involving the entire brain such as AD. Thereby, the breadth of brain tissue heterogeneity including complex gyri and sulci, compartmentalized gray and white matter, and large ventricles and blood vessels is being captured 33 . These are acoustically distinct structures and it is important to account for them when refining the obicodilation technique 61 .…”

Section: Discussionmentioning

confidence: 99%

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Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions

Pelekanos¹,

Leinenga²,

Odabaee³

et al. 2018

Theranostics

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Rationale: Treating diseases of the brain such as Alzheimer's disease (AD) is challenging as the blood-brain barrier (BBB) effectively restricts access of a large number of potentially useful drugs. A potential solution to this problem is presented by therapeutic ultrasound, a novel treatment modality that can achieve transient BBB opening in species including rodents, facilitated by biologically inert microbubbles that are routinely used in a clinical setting for contrast enhancement. However, in translating rodent studies to the human brain, the presence of a thick cancellous skull that both absorbs and distorts ultrasound presents a challenge. A larger animal model that is more similar to humans is therefore required in order to establish a suitable protocol and to test devices. Here we investigated whether sheep provide such a model.Methods: In a stepwise manner, we used a total of 12 sheep to establish a sonication protocol using a spherically focused transducer. This was assisted by ex vivo simulations based on CT scans to establish suitable sonication parameters. BBB opening was assessed by Evans blue staining and a range of histological tests.Results: Here we demonstrate noninvasive microbubble-mediated BBB opening through the intact sheep skull. Our non-recovery protocol allowed for BBB opening at the base of the brain, and in areas relevant for AD, including the cortex and hippocampus. Linear time-shift invariant analysis and finite element analysis simulations were used to optimize the position of the transducer and to predict the acoustic pressure and location of the focus.Conclusion: Our study establishes sheep as a novel animal model for ultrasound-mediated BBB opening and highlights opportunities and challenges in using this model. Moreover, as sheep develop an AD-like pathology with aging, they represent a large animal model that could potentially complement the use of non-human primates.

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Section: Introductionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions

Pelekanos¹,

Leinenga²,

Odabaee³

et al. 2018

Theranostics

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“…We previously reported our investigation on the effects of FUS on stimulation of the sensorimotor and visual cortices in an ovine model [31]. We chose to study sheep due to the structural similarities between the sheep and human craniums in regards to thickness, radius of curvature, and porosity [46, 47] and the neuroanatomical structures that are non-homogeneous and gyrencephalic [48]. Moreover, available clinical models of epilepsy [49], stroke [50], and brain injury [51] make sheep an attractive species to study en route to human application.…”

Section: Introductionmentioning

confidence: 99%

Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model

Yoon

Lee

et al. 2019

PLoS ONE

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Low-intensity focused ultrasound (FUS) has significant potential as a non-invasive brain stimulation modality and novel technique for functional brain mapping, particularly with its advantage of greater spatial selectivity and depth penetration compared to existing non-invasive brain stimulation techniques. As previous studies, primarily carried out in small animals, have demonstrated that sonication parameters affect the stimulation efficiency, further investigation in large animals is necessary to translate this technique into clinical practice. In the present study, we examined the effects of sonication parameters on the transient modification of excitability of cortical and thalamic areas in an ovine model. Guided by anatomical and functional neuroimaging data specific to each animal, 250 kHz FUS was transcranially applied to the primary sensorimotor area associated with the right hind limb and its thalamic projection in sheep (n = 10) across multiple sessions using various combinations of sonication parameters. The degree of effect from FUS was assessed through electrophysiological responses, through analysis of electromyogram and electroencephalographic somatosensory evoked potentials for evaluation of excitatory and suppressive effects, respectively. We found that the modulatory effects were transient and reversible, with specific sonication parameters outperforming others in modulating regional brain activity. Magnetic resonance imaging and histological analysis conducted at different time points after the final sonication session, as well as behavioral observations, showed that repeated exposure to FUS did not damage the underlying brain tissue. Our results suggest that FUS-mediated, non-invasive, region-specific bimodal neuromodulation can be safely achieved in an ovine model, indicating its potential for translation into human studies.

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“…There are currently no clinical data concerning skull trauma following bone graft harvesting in adults. But the authors of more recent studies on animals or fresh cadavers have reported a significant weakening of the harvesting site in case of external layer harvest (Laure et al, 2010(Laure et al, , 2011. However, only restricted conclusions can be made from animal-model studies because of anatomical differences between a human skull and an animal skull.…”

Section: Introductionmentioning

confidence: 99%

Comparative finite element analysis of skull mechanical properties following parietal bone graft harvesting in adults

Haen

Dubois

Goudot

et al. 2018

Journal of Cranio-Maxillofacial Surgery

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Resistance of the sheep skull after a monocortical cranial graft harvest

Cited by 10 publications

References 21 publications

Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions

Establishing sheep as an experimental species to validate ultrasound-mediated blood-brain barrier opening for potential therapeutic interventions

Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model

Comparative finite element analysis of skull mechanical properties following parietal bone graft harvesting in adults

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