Transverse Myelitis in the Setting of Enterobius vermicularis (Pinworm) Infection: Case Report.

Myelitis is a rare inflammatory myelopathy, and known associated etiologies only account for a small number of causes. A significant percentage of cases have an unknown etiology and are considered idiopathic. With 64% to 68% of cases fitting into the idiopathic category, helminth infections, and specifically pinworm parainfections, should be considered in cases that would otherwise be classified as idiopathic. This case report outlines a pediatric patient diagnosed with myelitis given her progressive weakness, fussiness, refusal to bear weight as well as magnetic resonance imaging (MRI) demonstrating T2-hyperintense signal and/or T1 gadolinium enhancement, and/or positive cerebrospinal fluid (CSF) inflammatory markers. This patient had a negative evaluation for typical known etiologies for myelitis including no signs of multiple sclerosis and neuromyelitis optica spectrum disorder on brain MRI, oligoclonal banding and aquaporin-4 autoantibodies, and no evidence of bacterial or viral meningitis given normal cell counts and cultures in CSF. She was found to have a pinworm infection, suggesting a parasitic parainfectious etiology of her myelitis. This case outlines the first case noting the correlation between myelitis and pinworm infection in a pediatric patient.

Prospective Review of Mesenchymal Stem Cells Differentiation into Osteoblasts.

Stem cell research has been a popular topic in the past few decades. This review aims to discuss factors that help regulate, induce, and enhance mesenchymal stem cell (MSC) differentiation into osteoblasts for bone regeneration. The factors analyzed include bone morphogenic protein (BMP), transforming growth factor ß (TGF-ß), stromal cell-derived factor 1 (SDF-1), insulin-like growth factor type 1 (IGF-1), histone demethylase JMJD3, cyclin dependent kinase 1 (CDK1), fucoidan, Runx2 transcription factor, and TAZ transcriptional coactivator. Methods promoting bone healing are also evaluated in this review that have shown promise in previous studies. Methods tested using animal models include low intensity pulsed ultrasound (LIPUS) with MSC, micro motion, AMD3100 injections, BMP delivery, MSC transplantation, tissue engineering utilizing scaffolds, anti-IL-20 monoclonal antibody, low dose photodynamic therapy, and bone marrow stromal cell transplants. Human clinical trial methods analyzed include osteoblast injections, bone marrow grafts, bone marrow and platelet rich plasma transplantation, tissue engineering using scaffolds, and recombinant human BMP-2. These methods have been shown to promote and accelerate new bone formation. These various methods for enhanced bone regeneration have the potential to be used, following further research, in clinical practice.

A comparison of neuroinflammation to implanted microelectrodes in rat and mouse models.

Rat models have emerged as a common tool to study neuroinflammation to intracortical microelectrodes. While a number of studies have attempted to understand the factors resulting in neuroinflammation using rat models, a complete understanding of key mechanistic pathways remains elusive. Transgenic mouse models, however, could facilitate a deeper understanding of mechanistic pathways due to an ease of genetic alteration. Therefore, the goal of the present study is to compare neuroinflammation following microelectrode implantation between the rat and the mouse model. Our study suggests that subtle differences in the classic neuroinflammatory markers exist between the animal models at both two and sixteen weeks post implantation. Most notably, neuronal densities surrounding microelectrodes were significantly lower in the rat model at two weeks, while similar densities were observed between the animal models at sixteen weeks. Physiological differences between the species and slight alterations in surgical methods are likely key contributors to the observed differences. Moving forward, we propose that differences in the time course of neuroinflammation between the animal models should be considered when trying to understand and prevent intracortical microelectrode failure.

The effect of resveratrol on neurodegeneration and blood brain barrier stability surrounding intracortical microelectrodes.

The current study seeks to elucidate a biological mechanism which may mediate neuroinflammation, and decreases in both blood-brain barrier stability and neuron viability at the intracortical microelectrode-tissue interface. Here, we have focused on the role of pro-inflammatory reactive oxygen species. Specifically, adult rats implanted within intracortical microelectrodes were systemically administered the anti-oxidant, resveratrol, both the day before and the day of surgery. Animals were sacrificed at two or four weeks post-implantation for histological analysis of the neuroinflammatory and neurodegenerative responses to the microelectrode. At two weeks post-implantation, we found animals treated with resveratrol demonstrated suppression of reactive oxygen species accumulation and blood-brain barrier instability, accompanied with increased density of neurons at the intracortical microelectrode-tissue interface. Four weeks post-implantation, animals treated with resveratrol exhibited indistinguishable levels of markers for reactive oxygen species and neuronal nuclei density in comparison to untreated control animals. However, of the neurons that remained, resveratrol treated animals were seen to display reductions in the density of degenerative neurons compared to control animals at both two and four weeks post-implantation. Initial mechanistic evaluation suggested the roles of both anti-oxidative enzymes and toll-like receptor 4 expression in facilitating microglia activation and the propagation of neurodegenerative inflammatory pathways. Collectively, our data suggests that short-term attenuation of reactive oxygen species accumulation and blood-brain barrier instability can result in prolonged improvements in neuronal viability around implanted intracortical microelectrodes, while also identifying potential therapeutic targets to reduce chronic intracortical microelectrode-mediated neurodegeneration.

Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses.

An estimated 25 million people in the US alone rely on implanted medical devices, ∼2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ∼50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.