Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C. elegans fed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.
Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog – like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson’s disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson’s disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.
Neuromyelitis Optica (NMO) is associated with antibodies to aquaporin 4 (AQP4). We hypothesized that antibodies to AQP4 can be triggered by exposure to environmental proteins. We compared human AQP4 to plant and bacterial proteins to investigate the occurrence of significantly similar structures and sequences. High similarity to a known epitope for NMO-IgG, AQP4(207-232), was observed for corn ZmTIP4-1. NMO and non-NMO serum was assessed for reactivity to AQP4(207-232) and the corn peptide. NMO patient serum showed reactivity to both peptides as well as to plant tissue. These findings warrant further investigation into the role of the environment in NMO etiology.
Puetz V, Sylaja PN, Coutts SB, et al. Extent of hypoattenuation onCT angiography source images predicts functional outcome in patients with basilar artery occlusion.
Introduction: Mechanical thrombectomy (MT) is a part of the standard treatment of LVO stroke. Peri-interventional blood pressure variability may impact the outcomes of MT. In this study, we assessed whether lower mean blood pressure levels for longer than 12 hours has any impact on the short-term functional outcomes of MT. Methods: With the approval of the Human Studies Committee at the University of Louisville (IRB #: 13.0396), we performed a retrospective analysis of LVO stroke MT patients from 2016-18 (n=86). Blood pressure (BP) data collected at admission baseline, precanalization, immediate post-canalization, and 24 hours post-canalization. Baseline and post-canalization 24-hour BP data collected hourly. MBP lower than 20% of the “mean baseline” values recorded in the first few hours of admission was considered as “ clinically low ” BP, and a total of 12 hours of clinically low MBP levels within the first 24-hour of post-thrombectomy period was considered as “ potentially hypoperfused ”. Changes in NIHSS within the first 24 hours post canalization and NIHSS at discharge were assessed as main outcomes. Results: Mean age was 65±13 years. About 83% of patients TICI 2b/3 was accomplished. Baseline MBP levels were 103 ± 16mmHg. When the “ potentially hypoperfused ” patients (MBP<80 of baseline for >12 hours) were compared with the patients who were not (n=29 vs. n=57), the change in NIHSS at 24 hours and the NIHSS score at discharge were statistically significantly worse in patients who were potentially hypoperfused . (Table) Discussion: In this retrospective analysis, we assessed the contribution of clinically lower MBP levels after MT to the short-term functional outcome. Our preliminary results showed that the patients who were exposed to hypoperfusion for longer than 12 hours had worse NIHSS scores. Impact of maintaining baseline blood pressure needs to be further studied under prospective and controlled study designs.
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