Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity.

Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation.

Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers.

Comparative specialization of intrinsic cardiac neurons in humans, mice and pigs.

Intrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exist. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry and ultrastructure of these neurons across species.

Comparative specialization of intrinsic cardiac neurons in humans, mice, and pigs.

Intrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exists. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs, and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry, and ultrastructure of these cells across species.

Nonbinary 2D Distribution Tool Maps Autonomic Nerve Fiber Clustering in Lumbosacral Ventral Roots of Rhesus Macaques.

Neuromodulation of the peripheral nervous system (PNS) by electrical stimulation may augment autonomic function after injury or in neurodegenerative disorders. Nerve fiber size, myelination, and distance between individual fibers and the stimulation electrode may influence response thresholds to electrical stimulation. However, information on the spatial distribution of nerve fibers within the PNS is sparse.

Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration.

Upon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate that is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site.

Bortezomib-induced neuropathy is in part mediated by the sensitization of TRPV1 channels.

TRPV1 is an ion channel that transduces noxious heat and chemical stimuli and is expressed in small fiber primary sensory neurons that represent almost half of skin nerve terminals. Tissue injury and inflammation result in the sensitization of TRPV1 and sustained activation of TRPV1 can lead to cellular toxicity though calcium influx. To identify signals that trigger TRPV1 sensitization after a 24-h exposure, we developed a phenotypic assay in mouse primary sensory neurons and performed an unbiased screen with a compound library of 480 diverse bioactive compounds.

Detrusor underactivity is associated with metabolic syndrome in aged primates.

Lower urinary tract (LUT) dysfunction is prevalent in the elderly population, and clinical manifestations include urinary retention, incontinence, and recurrent urinary tract infections. Age-associated LUT dysfunction is responsible for significant morbidity, compromised quality of life, and rising healthcare costs in older adults, but its pathophysiology is not well understood. We aimed to investigate the effects of aging on LUT function by urodynamic studies and metabolic markers in non-human primates.

A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves.

A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter.

High-throughput segmentation of unmyelinated axons by deep learning.

Axonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats.

Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces.

Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and predictability of neural interface performance. Here we use computational models of rat visceral nerve to predict how neuroanatomical variability could affect both electrical stimulation and recording with an experimental planar neural interface.We developed a hybrid computational pipeline,sceralervensembleecording andtimulation (ViNERS), to couple finite-element modelling of extracellular electrical fields with biophysical simulations of individual axons.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

[Figure: see text].

A shape-adjusted ellipse approach corrects for varied axonal dispersion angles and myelination in primate nerve roots.

Segmentation of axons in light and electron micrographs allows for quantitative high-resolution analysis of nervous tissues, but varied axonal dispersion angles result in over-estimates of fiber sizes. To overcome this technical challenge, we developed a novel shape-adjusted ellipse (SAE) determination of axonal size and myelination as an all-inclusive and non-biased tool to correct for oblique nerve fiber presentations. Our new resource was validated by light and electron microscopy against traditional methods of determining nerve fiber size and myelination in rhesus macaques as a model system.

Sexual dimorphism of detrusor function demonstrated by urodynamic studies in rhesus macaques.

The lower urinary tract (LUT) and micturition reflexes are sexually dimorphic across mammals. Sex as a biological variable is also of critical importance for the development and translation of new medical treatments and therapeutics interventions affecting pelvic organs, including the LUT. However, studies of LUT function with comparisons between the sexes have remained sparse, especially for larger mammals.

Ketamine-induced neuromuscular reactivity is associated with aging in female rhesus macaques.

Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized.

Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease.

Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on myelin and axon loss in MS, less is known about mechanisms underlying synaptic changes. Using postmortem human MS tissue, a preclinical nonhuman primate model of MS, and two rodent models of demyelinating disease, we investigated synapse changes in the visual system.

Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1) of ALS.

Background: The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50 mg/kg) presents therapeutic potential in SOD1 transgenic mice.

Fibrin biopolymer as scaffold candidate to treat bone defects in rats.

Background: Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties.

Traceability of animal protein byproducts in ruminants by multivariate analysis of isotope ratio mass spectrometry to prevent transmission of prion diseases.

Background: Ruminant feed containing animal byproduct proteins (ABPs) is prohibited in many countries due to its risk of transmitting prion diseases (PD). In most cases the entire herd is sacrificed, which causes great harm to the producer countries by preventing their exportation of ruminant derived-products.

Methods: We used stable isotope ratio mass spectrometry (IRMS) of carbon (C/C) and nitrogen (N/N) to trace the animal protein in the blood of 15 buffaloes () divided into three experimental groups: 1 - received only vegetable protein (VP) during 117 days; 2 - received animal and vegetable protein (AVP); and 3 - received animal and vegetable protein with animal protein subsequently removed (AVPR).

Multiple uses of fibrin sealant for nervous system treatment following injury and disease.

Lesions to the nervous system often produce hemorrhage and tissue loss that are difficult, if not impossible, to repair. Therefore, scar formation, inflammation and cavitation take place, expanding the lesion epicenter. This significantly worsens the patient conditions and impairment, increasing neuronal loss and glial reaction, which in turn further decreases the chances of a positive outcome.