scholarly journals Electrophysiological Signature Reveals Laminar Structure of the Porcine Hippocampus

2017 ◽  
Author(s):  
Alexandra V. Ulyanova ◽  
Paul F. Koch ◽  
Carlo Cottone ◽  
Michael R. Grovola ◽  
Christopher D. Adam ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Single Unit ◽  
Dorsal Hippocampus ◽  
Region Of Interest ◽  
Large Animal ◽  
Field Potentials ◽  
Laminar Structure ◽  
Large Animal Models ◽  
Silicon Probes

AbstractThe hippocampus is integral to working and episodic memory, and is a central region of interest in diseases affecting these processes. Pig models are widely used in translational research, and may provide an excellent bridge between rodents and non-human primates for CNS disease models due to their gyrencephalic neuroanatomy and significant white matter composition. However, the laminar structure of the pig hippocampus has not been well characterized. Therefore, we histologically characterized the dorsal hippocampus of Yucatan miniature pigs and quantified the cytoarchitecture of the hippocampal layers. We then utilized stereotaxis combined with single unit electrophysiological mapping to precisely place multichannel laminar silicon probes into the dorsal hippocampus without the need for image guidance. We usedin vivoelectrophysiological recordings of simultaneous laminar field potentials and single unit activity in multiple layers of the dorsal hippocampus to physiologically identify and quantify these layers under anesthesia. Consistent with previous reports, we found the porcine hippocampus to have the expected archicortical laminar structure with some anatomical and histological features comparable to the rodent and others to the primate hippocampus. Importantly, we found these distinct features to be reflected in the laminar electrophysiology. This characterization, as well as our electrophysiology-based methodology targeting the porcine hippocampal lamina combined with high channel count silicon probes will allow for analysis of spike-field interactions during normal and disease states in both anesthetized and future awake behaving neurophysiology in this large animal.Significance StatementThe hippocampus is central to working and episodic memory and is critically affected by diverse disease processes. In order to investigate hippocampal electrophysiology in translational large animal models, we developed an imaging-free stereotaxis and intraoperative electrophysiology methodology with custom silicon probes to precisely localize probe placement within the hippocampal laminar structure. We report for the first time the profile of single units and local field potentials in the pig dorsal hippocampus and relate them to a histological description. This characterization forms the basis for accessible translational pig models to study diseases of the central nervous system affecting hippocampal circuitry in the large animal gyrencephalic brain, as well as the groundwork for potential awake behaving neurophysiology of the porcine hippocampus.Funding SourcesThe Department of Veterans Affairs, IK2-RX001479, I01-RX001097. The National Institutes of Health, NINDS R01-NS-101108-01, T32-NS043126. CURE Foundation, Taking Flight Award. DoD ERP CDMRP, W81XWH-16-1-0675.

scholarly journals Multichannel Silicon Probes for Awake Hippocampal Recordings in Large Animals

2018 ◽  
Author(s):  
Alexandra V. Ulyanova ◽  
Carlo Cottone ◽  
Christopher D. Adam ◽  
Kimberly G. Gagnon ◽  
D. Kacy Cullen ◽  
...  
Keyword(s):  
Single Unit ◽  
Brain Structures ◽  
Neural Interface ◽  
Large Animal ◽  
Cross Sectional ◽  
Large Animal Models ◽  
Cortical Regions ◽  
Over Time ◽  
Deep Brain ◽  
Silicon Probes

AbstractDecoding laminar information across deep brain structures and cortical regions is necessary in order to understand the spatiotemporal ensembles that represent cognition and memory. Large animal models are essential for translational research due to their gyrencephalic neuroanatomy and significant white matter composition. One of the major obstacles to applying the approaches currently utilized in lower order animals are technical limitations in silicon probes, specifically a lack of long-length probes with appropriate stiffness to penetrate to deeper structures with minimal damage to the neural interface. We tested various solutions and designs of multichannel silicon probes developed for large animal electrophysiology by recording neurophysiological signals from deep laminar structures in an acute preparation and in chronically implanted awake behaving Yucatan pigs. Electrophysiological parameters of single units and local field potentials were analyzed to evaluate performance over time of given silicon probes in chronic implantations. The cross-sectional area of silicon probes was found to be a crucial determinant of silicon probes’ single unit performance over time, potentially due to reduction of damage to the neural interface. EDGE-style probes had the highest yields during intra-hippocampal recordings in pigs, making them the most suitable for chronic implantations and awake behavioral experimentation. Novel CAMB 64-channel EDGE-style probes with linear and poly-2 site arrangement tested acutely had optimal single unit separation and a denser sampling of the laminar structure, identifying them as potential candidates for chronic implantations with less cortical damage above the active portion of the probe. This study provides an analysis of multichannel silicon probes designed for large animal laminar electrophysiology of deep brain structures, and suggests that current designs are reaching the physical thresholds necessary for long-term (~ 1 month) recordings from laminar deep structures with single-unit resolution.

scholarly journals Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 713
Author(s):  
Shu Fang ◽  
Ditte Gry Ellman ◽  
Ditte Caroline Andersen
Keyword(s):  
Animal Models ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Large Animal ◽  
Large Animal Models ◽  
Graft Outcome ◽  
Limited Success ◽  
Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

A Systematic Review of the Tensile Biomechanical Properties of the Neonatal Brachial Plexus

2021 ◽  
Author(s):  
Virginia Orozco ◽  
Rachel Magee ◽  
Sriram Balasubramanian ◽  
Anita Singh
Keyword(s):  
Brachial Plexus ◽  
Biomechanical Properties ◽  
Large Animal ◽  
Comprehensive Overview ◽  
Related Factors ◽  
Large Animal Models ◽  
Biomechanical Responses ◽  
Biomechanical Parameters ◽  
Injury Outcomes

Abstract Brachial plexus birth injury has a reported incidence of 1 to 4 per 1000 live births. During complicated deliveries, neonatal, maternal, and other birth-related factors can cause over-stretching or avulsion of the neonatal brachial plexus leading to injury. Understanding biomechanical responses of the neonate brachial plexus when subjected to stretch can offer insight into the injury outcomes while guiding the development of preventative maneuvers that can help reduce the occurrence of neonatal brachial plexus injuries. This review article aims to offer a comprehensive overview of existing literature reporting biomechanical responses of the brachial plexus, in both adults and neonates, when subjected to stretch. Despite the discrepancies in the reported biomechanical properties of the brachial plexus, the studies confirm the loading rate and loading direction dependency of the brachial plexus tissue. Future studies, possibly in vivo, that utilize clinically-relevant neonatal large animal models can provide translational failure values of the biomechanical parameters for the neonatal brachial plexus when subjected to stretch.

scholarly journals In vivo cerebral aneurysm models

2019 ◽  
Vol 47 (1) ◽  
pp. E20 ◽  
Author(s):  
John W. Thompson ◽  
Omar Elwardany ◽  
David J. McCarthy ◽  
Dallas L. Sheinberg ◽  
Carlos M. Alvarez ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Surgical Techniques ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Large Animal ◽  
Pharmacological Interventions ◽  
Large Animal Models ◽  
First Line Therapy ◽  
Endovascular Devices

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

scholarly journals Consequences of mitral valve prolapse on chordal tension: Ex vivo and in vivo studies in large animal models

2011 ◽  
Vol 142 (6) ◽  
pp. 1585-1587 ◽  
Author(s):  
Mathieu Granier ◽  
Morten O. Jensen ◽  
Jesper L. Honge ◽  
Alain Bel ◽  
Philippe Menasché ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Animal Models ◽  
Mitral Valve Prolapse ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Large Animal ◽  
Large Animal Models

scholarly journals Adult Canine Intestinal Derived Organoids: A Novel In Vitro System for Translational Research in Comparative Gastroenterology

2018 ◽  
Author(s):  
Lawrance Chandra ◽  
Dana C Borcherding ◽  
Dawn Kingsbury ◽  
Todd Atherly ◽  
Yoko M Ambrosini ◽  
...  
Keyword(s):  
Animal Models ◽  
Translational Research ◽  
Three Dimensional ◽  
Metabolic Imaging ◽  
Large Animal ◽  
Large Animal Models ◽  
Molecular Features ◽  
Naturally Occurring

AbstractBackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.ResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.ConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.

scholarly journals Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone

2018 ◽  
Vol 24 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Banu Akar ◽  
Alexander M. Tatara ◽  
Alok Sutradhar ◽  
Hui-Yi Hsiao ◽  
Michael Miller ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Large Animal Models ◽  
Vascularized Bone

scholarly journals Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw4357 ◽  
Author(s):  
Jinqiang Wang ◽  
Jicheng Yu ◽  
Yuqi Zhang ◽  
Xudong Zhang ◽  
Anna R. Kahkoska ◽  
...  
Keyword(s):  
Animal Models ◽  
Insulin Release ◽  
Phenylboronic Acid ◽  
Insulin Delivery ◽  
Fast Response ◽  
Diabetic Mouse ◽  
Glucose Sensing ◽  
Large Animal ◽  
Large Animal Models

Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.

scholarly journals Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 230
Author(s):  
Girish Pattappa ◽  
Jonas Krueckel ◽  
Ruth Schewior ◽  
Dustin Franke ◽  
Alexander Mench ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Large Animal ◽  
Large Animal Models ◽  
Early Oa

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

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