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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Bio-Imitation of Mexican Migration Routes to the USA with Slime Mould on 3D Terrains

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journal of Bionic Engineering 2013年第2期10卷 242-250页

作者： andrew Adamatzky Genaro j Martinez Department of Computer Sciences University of the West of England Bristol BS16 1QY UK Escuela Superior de Computo Instituto Politecnico Nacional Mexico

Plasmodium ofPhysarum polycephalum （P. polycephalum） is a large single cell visible by an unaided eye. It shows sophisticated behavioural traits in foraging for nutrients and developing an optimal transport network of protoplasmic tubes spanning sources of nutrients. When placed in an environment with distributed sources of nutrients the cell computes＇ an optimal graph spanning the nutrients by growing a network of protoplasmic tubes. P. polycephalum imitates development ofman-made transport networks of a country when configuration of nutrients represents major urban areas, We employed this feature of the slime mould to imitate mexican migration to USA. The Mexican migration to USA is the World＇s larger migration system. We bio-physically imitated the migration using slime mould P. poIycephalum. In laboratory experiments with 3D Nylon terrains of USA we imitated development of migratory routes from Mexico-USA border to ten urban areas with high concentration of Mexican migrants. From results of laboratory experiments we extracted topologies of migratory routes, and highlighted a role of elevations in shaping the human movement networks.

关键词： biomimetics bio-inspired computing migration routes slime mould

The ethical cost of doing nothing

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National Science Review 2020年第7期7卷 1260-1262页

作者： andrew j.Parker University of Oxford Department of PhysiologyAnatomy and Genetics

Concern has been raised about the ethics and risks of performing genetic interventions in macaque monkeys to study models of human neuropsychiatric conditions. Here I point out that,when the outcome of some situations is truly uncertain, human decision makers tend to evaluate these situations inconsistently. The consequences of this inconsistency are sometimes profound, as they lead policy makers and reviewers to ignore or discount the ethical costs of doing nothing. I conclude that there are fundamental problems with the ‘precautionary

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Testing decreasing variabililty of cockroach forewings through time using four Recent species： Blattella germanica, Polyphaga aegyptiaca, Shelfordella lateralis and Blaberus craniifer, with implications for the study of fossil cockroach forewings

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Insect Science 2012年第2期19卷 129-142页

作者： andrew j. Ross Department of Natural Sciences National Museums Scotland Edinburgh UK

Vrsansky, （2000） considered there is decreasing variability in the forewings of cockroaches through time, based on a study of fossil and Recent species. This study tests his theory, based on a study of four Recent species of cockroaches： Blattella germanica （Blattellidae）, Polyphaga aegyptiaca （Polyphagidae）, Shelfordella lateralis （Blattidae） and Blaberus craniifer （Blaberidae）. The new results, based on the coefficient of variation （CV） of the number of veins, indicate that Recent species can be more variable than fossil species and therefore do not support the theory. The results also show that at least 30 complete wings of the same species are required for a reliable CV value that is compa- rable between species.

关键词： Blaberidae Blattellidae Blattidae cockroach Polyphagidae variation

Advances in diagnostic testing for gastroesophageal reflux disease

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World journal of Gastroenterology 2010年第30期16卷 3750-3756页

作者： andrew j Gawron Ikuo Hirano Division of Gastroenterology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoIL 60611-2951United States

Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology.

关键词： Gastroesophageal reflux disease pH impedance pH monitoring Symptom association

Teleseismic waves reveal anisotropic poroelastic response of wastewater disposal reservoir

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Earth and Planetary Physics 2021年第6期5卷 547-558页

作者： andrew j Barbour Nicholas M Beeler u.s.geological survey earthquake science centerusa

Connecting earthquake nucleation in basement rock to fluid injection in basal,sedimentary reservoirs,depends heavily on choices related to the poroelastic properties of the fluid-rock system,thermo-chemical effects *** constraints on these parameters outside of laboratory settings are rare,and it is commonly assumed that the rock layers are *** the Arbuckle wastewater disposal reservoir in Osage County,Oklahoma,high-frequency formation pressure changes and collocated broadband ground velocities measured during the passing of large teleseismic waves show a poroelastic response of the reservoir that is both azimuthally variable and anisotropic;this includes evidence of static shifts in pressure that presumably relate to changes in local *** azimuthal dependence in both the static response and shear coupling appears related to tectonic stress and strain indicators such as the orientations of the maximum horizontal stress and faults and *** dynamic strains from a nearby borehole strainmeter,we show that the ratio of shear to volumetric strain coupling is~0.41 which implies a mean Skempton's coefficient of A=0.24 over the plausible range of the undrained Poisson's *** these observations are made at relatively low confining pressure and differential stress,we suggest that the hydraulically conductive fracture network is a primary control on the coupling between pore pressure diffusion and elastic stresses in response to natural or anthropogenic sources.

关键词： poroelasticity dynamic strain anisotropy wastewater disposal Oklahoma induced seismicity

Sexual dimorphism in cranial shape and size in geomyoid rodents:multivariate and evolutionary perspectives

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Current Zoology 2022年第4期68卷 469-487页

作者： jonathan j M Calede andrew Brown Department of Evolution Ecologyand Organismal BiologyThe Ohio State University318 W.12th Ave.300 Aronoff LaboratoryColumbusOH 43210USA The Ohio State University at Marion 1459 Mount Vernon AvenueMarionOH 43302USA College of Veterinary Medicine Texas A&M University660 Raymond Stotzer PkwyCollege StationTX 77843USA

Geomyoid rodents provide a great study system for the analysis of sexual *** are polygynic and many inhabit harsh arid environments thought to promote sexual *** fact,there has been extensive work published on the sexual size dimorphism of individual populations and species within this rodent ***,little work has been undertaken to assess the evolutionary patterns and processes associated with this sexual *** use multivariate analyses of cranial measurements in a phylogenetic framework to determine the distribution of size and shape dimorphism among geomyoids and test for Rensch’s *** results suggest that sexual dimorphism is more common in geomyids than heteromyids,but it is not in fact *** is evidence for variation in sexual dimorphism across ***,in many taxa,geographic variation appears to overwhelm existing sexual *** find support for the repeated independent evolution of shape and size dimorphism across geomyoid taxa,but we do not find support for an association between size and shape *** is no evidence for Rensch’s rule in geomyoids,whether at the superfamily or family ***,our findings suggest that there is no single explanation for the evolution of sexual dimorphism in geomyoids and that,instead,it is the product of numerous evolutionary *** studies incorporating phylogenetic relationships will be necessary to paint a more complete picture of the evolution of sexual dimorphism in geomyoids.

关键词： Geomyidae Heteromyidae phylogenetic comparative methods morphometrics Rensch’s rule

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia