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BackgroundPhysical inactivity increases the risk for metabolic diseases such as obesity and type 2 diabetes. Neuromuscular electrical stimulation (NMES) is an effective method to induce muscle contraction, particularly for populations with physical impairments and/or metabolic diseases. However, its effectiveness to improve glycemic control is unclear. This review aimed to determine the effectiveness of NMES on glycemic control.MethodsElectronic search consisted of MEDLINE (PubMed), EMBASE, Cochrane Library, Google Scholar, and Web of Science to identify studies that investigated the effects of NMES on glycemic control for this systematic review. The meta-analysis consists of the studies designed as randomized controlled trials. Effect sizes were calculated as the standardized mean difference (SMD) and meta-analysis was conducted using a random-effects model.ResultsThirty-five studies met the inclusion criteria for systematic review and of those, nine qualified for the meta-analysis. Existing evidence suggested that NMES effectively improves glycemic control predominantly in middle-aged and elderly population with type 2 diabetes, obesity, and spinal cord injury. The meta-analysis is comprised of 180 participants and reported that NMES intervention lowered fasting blood glucose (SMD: 0.48; 95% CI: 0.17 to 0.78; p=0.002; I²=0%). Additional analysis using the primary measures reported by each study to indicate glycemic control (i.e., OGTT, HOMA-IR, and fasting glucose) also confirmed a significant effect of NMES on improving glycemic control (SMD: 0.41; 95% CI, 0.09 to 0.72; p=0.01; I²=11%). NMES protocol varied across studies and requires standardization.ConclusionNMES could be considered as a therapeutic strategy to improve glycemic control in populations with physical impairments and/or metabolic disorders.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020192491.

Viral encephalitis is a major cause of morbidity and mortality, but the manifestation of disease varies greatly between individuals even in response to the same virus. Microglia are professional antigen presenting cells that reside in the central nervous system (CNS) parenchyma that are poised to respond to viral insults. However, the role of microglia in initiating and coordinating the antiviral response is not completely understood. Utilizing Theiler’s murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, and PLX5622, a small molecule inhibitor of colony-stimulating factor 1 receptor (CSF1R) signaling that can deplete microglia in the CNS; we investigated the role of the CSF1R-microglia axis in neurotropic picornavirus infection of C57BL/6J and SJL/J mice. These mouse strains differ in their ability to clear TMEV and exhibit different neurological disease in response to TMEV infection. CSF1R antagonism in C57BL/6J mice, which normally clear TMEV in the CNS, led to acute fatal encephalitis. In contrast, CSF1R antagonism in SJL/J mice, which normally develop a chronic CNS TMEV infection, did not result in acute encephalitis, but exacerbated TMEV-induced demyelination. Immunologically, inhibition of CSF1R in C57BL/6J mice reduced major histocompatibility complex II expression in microglia, decreased the proportion of regulatory T cells in the CNS, and upregulated proinflammatory pathways in CNS T cells. Acute CSF1R inhibition in SJL/J mice had no effect on microglial MHC-II expression and upregulated anti-inflammatory pathways in CNS T cells, however chronic CSF1R inhibition resulted in broad immunosuppression. Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.

The central nervous system (CNS) is an important regulator of the gastrointestinal tract, and CNS dysfunction can result in significant and disabling gastrointestinal symptom manifestation. For patients with neuroimmunologic and neuroinflammatory conditions, the recognition of gastrointestinal symptoms is under-appreciated, yet the gastrointestinal manifestations have a dramatic impact on quality of life. The current treatment strategies, often employed independently by the neurologist and gastroenterologist, raise the question of whether such patients are being treated optimally when siloed in one specialty. Neuroimmunogastroenterology lies at the borderlands of medical specialties, and there are few resources to guide neurologists in this area. Here, we provide an overview highlighting the potential mechanisms of crosstalk between immune-mediated neurological disorders and gastrointestinal dysfunction.