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Background and Purpose: Spinal cord stimulation (SCS) is approved by the Food and Drug Administration for treating chronic intractable pain in the back, trunk, or limbs through stimulation of the dorsal column. Numerous studies have used swine as an analog of the human spinal cord to better understand SCS and further improve its efficacy. We performed high‐resolution imaging of the porcine spinal cord with intact dura mater using micro‐computed tomography (μCT) to construct detailed 3‐dimensional (3D) visualizations of the spinal cord and characterize the morphology of the dorsal and ventral rootlets. Methods: We obtained spinal cords from Yorkshire/Landrace crossbred swine (N = 7), stained samples with osmium tetroxide, and performed μCT imaging of the T12‐T15 levels at isotropic voxel resolutions ranging from 3.3 to 50 μm. We measured the anatomical morphology using the 3D volumes and compared our results to measurements previously collected from swine and human spinal cords via microdissection techniques in prior literature. Results: While the porcine thoracic‐lumbar spinal cord is a popular model for SCS, we highlight multiple notable differences compared to previously published T8‐T12 human measurements including rootlet counts (porcine dorsal/ventral: 12.2 ± 2.6, 26.6 ± 3.4; human dorsal/ventral: 5.3 ± 1.3, 4.4 ± 2.4), rootlet angles (porcine ventral‐rostral: 161 ± 1°, ventral‐caudal: 155 ± 6°, dorsal‐rostral: 148 ± 9°, dorsal‐caudal: 142 ± 6°; human ventral‐rostral: 170 ± 3°, ventral‐caudal: 22 ± 10°, dorsal‐rostral: 171 ± 3°, dorsal‐caudal: 15 ± 7°), and the presence and count of dorsal rootlet bundles. Conclusions: Detailed measurements and highlighted differences between human and porcine spinal cords can inform variations in modeling and electrophysiological experiments between the two species. In contrast to other approaches for measuring the spinal cord and rootlet morphology, our method keeps the dura intact, reducing potential artifacts from dissection. [ABSTRACT FROM AUTHOR]

The liver differs from other organs in that two vascular systems deliver its blood - the hepatic artery and the portal vein. However, how the two systems interact is not fully understood. We therefore studied the microvascular geometry of rat liver hepatic artery and portal vein injected with the contrast polymer Microfil®. Intact isolated rat livers were imaged by micro- CT and anatomic evidence for hepatic arteriolo-portal venular shunts occurring between hepatic artery and portal vein branches was found. Simulations were performed to rule out the possibility of the observed shunts being artifacts resulting from image blurring. In addition, in the case of specimens where only the portal vein was injected, only the portal vein was opacified, whereas in hepatic artery injections, both the hepatic artery and portal vein were opacified. We conclude that mixing of the hepatic artery and portal vein blood can occur proximal to the sinusoidal level, and that the hepatic arteriolo-portal venular shunts may function as a one-way valve-like mechanism, allowing flow only from the hepatic artery to the portal vein (and not the other way around). [ABSTRACT FROM AUTHOR]

L7595 --> 960.7 --> Appropriately designed electrodes to make in vivo recordings of neural activity have been essential to understanding the nervous system. Recording electrode design has been extensively explored for use in measurement of naturally occurring neural activity in the brain. Recently, recordings of evoked compound action potentials (ECAPs) in the periphery have garnered interest due to their relevance in neuromodulation therapies for determining target engagement and enabling closed‐loop operation. Here, we compare three types of recording electrodes – microelectrodes, cuff electrodes, and intrafascicular electrodes – and their ability to make in vivo recordings of electrically ECAPs, naturally occurring neural activity, and sensory evoked neural activity in the peripheral nerves of a human‐relevant large animal model. The great auricular nerve, innervating the auricle, and cervical vagus nerve of domestic pigs were instrumented with the three recording electrodes. Naturally occurring neural activity, sensory evoked neural activity induced by gentle brushing of the auricle, and electrically ECAPs initiated by non‐invasive and invasive stimulation electrodes were recorded. The study was pre‐registered (https://osf.io/y9k6j). We showed that the recording cuff had superior performance in measuring invasive electrically ECAPs (p < 0.05) while the tungsten microelectrode, routinely used for microneurography in humans, had superior performance in measuring naturally occurring action potentials (p < 0.05). The microelectrode was still able to record electrically ECAPs. Further, we show how choice of reference electrode position may be optimized per application. Microneurography recordings paired with the deployment of a non‐invasive neuromodulation therapy can be used to functionally map sensory innervation areas in patients, allowing individualized placement of stimulation electrodes to achieve on‐target neural fiber activation. These findings provide a basis to select recording electrode type and configuration for measurement of neural signals in the development and deployment of neuromodulation therapies. [ABSTRACT FROM AUTHOR]

Aim: Small animal models chimeric for human hepatocytes have provided valuable insights into the biology of hepatotropic viral infection and provided a platform for the study of therapeutic agents. Existing models of human hepatocyte transplantation are limited by phenotypic fragility and impaired immunity. We hypothesized that mice transgenic for human hepatocyte growth factor (HGF), a potent human hepatocyte mitogen, would engraft human hepatocytes in the absence of immunodeficiency. Methods: A plasmid construct containing the 2.3 kb coding region of the 723 amino acid isoform of HGF cDNA under the transcriptional control of the mouse albumin promoter/enhancer was used to generate transgenic mice. Cryopreserved human hepatocytes were transplanted into nine transgenic and six non-transgenic mice. Engraftment of human hepatocytes was followed for a period of 12 weeks by immunoblotting for human albumin in mouse serum samples. Results: In six out of the nine transgenic mice, abundance of human albumin, following an initial decline, increased andpeaked at > 70 days post transplantation, demonstrating sustained engraftment of transplanted human hepatocytes. In all the non-transgenic mice, post-transplant human albumin levels declined sequentially without evidence of sustained engraftment. Immunostaining of mouse liver sections indicated the presence of human hepatocytes adjacent to clusters of non-staining murine hepatocytes. Conclusion: These results demonstrate that sustained engraftment of human hepatocytes in mice is facilitated by expression of the human dHGF transgene. Human hepatocyte engraftment in this model has been achieved on an immunocompetent strain background and merits further study as a candidate for the study of hepatotropic viral infections. [ABSTRACT FROM AUTHOR]

Discusses whether spontaneous fusion of cells between species could occur physiologic conditions. Contribution of human-porcine hybrids to porcine epithelial tissues; Role of cell fusion as a route for viral transmission.