Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabol...Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.展开更多
This manuscript provides a comparison of the Hypersphere World-Universe Model (WUM) with the prevailing Big Bang Model (BBM) of the Standard Cosmology. The performed analysis of BBM shows that the Four Pillars of the ...This manuscript provides a comparison of the Hypersphere World-Universe Model (WUM) with the prevailing Big Bang Model (BBM) of the Standard Cosmology. The performed analysis of BBM shows that the Four Pillars of the Standard Cosmology are model-dependent and not strong enough to support the model. The angular momentum problem is one of the most critical problems in BBM. Standard Cosmology cannot explain how Galaxies and Extra Solar systems obtained their substantial orbital and rotational angular momenta, and why the orbital momentum of Jupiter is considerably larger than the rotational momentum of the Sun. WUM is the only cosmological model in existence that is consistent with the Law of Conservation of Angular Momentum. To be consistent with this Fundamental Law, WUM discusses in detail the Beginning of the World. The Model introduces Dark Epoch (spanning from the Beginning of the World for 0.4 billion years) when only Dark Matter Particles (DMPs) existed, and Luminous Epoch (ever since for 13.8 billion years). Big Bang discussed in Standard Cosmology is, in our view, transition from Dark Epoch to Luminous Epoch due to Rotational Fission of Overspinning Dark Matter (DM) Supercluster’s Cores. WUM envisions Matter carried from the Universe into the World from the fourth spatial dimension by DMPs. Ordinary Matter is a byproduct of DM annihilation. WUM solves a number of physical problems in contemporary Cosmology and Astrophysics through DMPs and their interactions: Angular Momentum problem in birth and subsequent evolution of Galaxies and Extrasolar systems—how do they obtain it;Fermi Bubbles—two large structures in gamma-rays and X-rays above and below Galactic center;Diversity of Gravitationally-Rounded Objects in Solar system;some problems in Solar and Geophysics [1]. WUM reveals Inter-Connectivity of Primary Cosmological Parameters and calculates their values, which are in good agreement with the latest results of their measurements.展开更多
The aim of this work is mathematical education through the knowledge system and mathematical modeling. A net model of formation of mathematical knowledge as a deductive theory is suggested here. Within this model the ...The aim of this work is mathematical education through the knowledge system and mathematical modeling. A net model of formation of mathematical knowledge as a deductive theory is suggested here. Within this model the formation of deductive theory is represented as the development of a certain informational space, the elements of which are structured in the form of the orientated semantic net. This net is properly metrized and characterized by a certain system of coverings. It allows injecting net optimization parameters, regulating qualitative aspects of knowledge system under consideration. To regulate the creative processes of the formation and realization of mathematical know- edge, stochastic model of formation deductive theory is suggested here in the form of branching Markovian process, which is realized in the corresponding informational space as a semantic net. According to this stochastic model we can get correct foundation of criterion of optimization creative processes that leads to “great main points” strategy (GMP-strategy) in the process of realization of the effective control in the research work in the sphere of mathematics and its applications.展开更多
Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a posit...Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic(phrenic nerve group), intercostal(intercostal nerve group) or thoracodorsal nerves(thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.展开更多
Previous animal studies of cauda equina injury have primarily used rat models, which display significant differences from humans. Furthermore, most studies have focused on electrophysio- logical examination. To better...Previous animal studies of cauda equina injury have primarily used rat models, which display significant differences from humans. Furthermore, most studies have focused on electrophysio- logical examination. To better mimic the outcome after surgical repair of cauda equina injury, a novel animal model was established in the goat. Electrophysiological, histological and magnetic resonance imaging methods were used to evaluate the morphological and functional outcome after cauda equina injury and end-to-end suture. Our results demonstrate successful establish- ment of the goat experimental model of cauda equina injury. This novel model can provide detailed information on the nerve regenerative process following surgical repair of cauda equina injury.展开更多
Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic e...Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.展开更多
The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric an...The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intr...The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.展开更多
Alzheimer’s disease is one of the most frequent neurodegenerative diseases.This pathology is characterized by protein aggregates,mainly constituted by amyloid peptide and tau,leading to neuronal death and cognitive i...Alzheimer’s disease is one of the most frequent neurodegenerative diseases.This pathology is characterized by protein aggregates,mainly constituted by amyloid peptide and tau,leading to neuronal death and cognitive impairments.Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies.However,stilbenes presenting multiple pharmacological effects could be good potential therapeutic candidates.The aim of this review is to gather the more significant papers among the broad literature on this topic,concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer’s disease.Indeed,numerous studies focus on cellular models,but an in vivo approach remains of primary importance since in animals (mice or rats,generally),bioavailability and metabolism are taken into account,which is not the case in in vitro studies.Furthermore,examination of memory ability is feasible in animal models,which strengthens the relevance of a compound with a view to future therapy in humans.This paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in humans.This review shows that resveratrol,the reference polyphenol,is largely studied and seems to have interesting properties on amyloid plaques,and cognitive impairment.However,some resveratrol derivatives such as gnetin C,trans-piceid,or astringin have never been tested on animals.Furthermore,pterostilbene is of particular interest,by its improvement of cognitive disorders and its neuroprotective role.It could be relevant to evaluate this molecule in clinical trials.展开更多
Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure ...Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.展开更多
Objective:Peripheral nerve repair is required after traumatic injury.This common condition represents a major public health problem worldwide.Recovery after nerve repair depends on several factors,including the severi...Objective:Peripheral nerve repair is required after traumatic injury.This common condition represents a major public health problem worldwide.Recovery after nerve repair depends on several factors,including the severity of the injury,the nerve involved,and the surgeon’s technical skills.Despite the precise microsurgical repair of nerve lesions,adequate functional recovery is not always achieved and,therefore,the regeneration process and surgical techniques are still being studied.Pre-clinical animal models are essential for this research and,for this reason,the focus of the present systematic review(according to the PRISMA statement)was to analyze the different animal models used in pre-clinical peripheral nerve repair studies.Data sources:Original articles,published in English from 2000 to 2018,were collected using the Web of Science,Scopus,and PubMed databases.Data selection:Only preclinical trials on direct nerve repair were included in this review.The articles were evaluated by the first two authors,in accordance with predefined data fields.Outcome measures:The primary outcomes included functional motor abilities,daily activity and regeneration rate.Secondary outcomes included coaptation technique and animal model.Results:This review yielded 267 articles,of which,after completion of the screening,49 studies were analyzed.There were 1425 animals in those 49 studies,being rats,mice,guinea pigs,rabbits,cats and dogs the different pre-clinical models.The nerves used were classified into three groups:head and neck(11),forelimb(8)and hindlimb(30).The techniques used to perform the coaptation were:microsuture(46),glue(12),laser(8)and mechanical(2).The follow-up examinations were histology(43),electrophysiological analysis(24)and behavioral observation(22).Conclusion:The most widely used animal model in the study of peripheral nerve repair is the rat.Other animal models are also used but the cost-benefit of the rat model provides several strengths over the others.Suture techniques are currently the first option for nerve repair,but the use of glues,lasers and bioengineering materials is increasing.Hence,further research in this field is required to improve clinical practice.展开更多
In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory fail...In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.展开更多
In this paper we will see the model of Universe according to Dynamic Universe Model of Cosmology by visualizing various processes that are happening in the Universe as per experimental evidences. For simplifying the m...In this paper we will see the model of Universe according to Dynamic Universe Model of Cosmology by visualizing various processes that are happening in the Universe as per experimental evidences. For simplifying the matter here, we will see in part 1: about the Galaxy life cycle, where the birth and death of Galaxies discussed. Probably Universe gives guidance for the movement of Galaxies. We call this Part 1: Thinking and Reproducing Universe or Mindless Universe? (Galaxy life cycle). We see every day Sun, Stars, Galaxies etc., dissipating enormous energy in the form of radiation by the way of fusion of Hydrogen to helium. So after sometime all the Hydrogen is spent and Universe will die, is it not? … Dynamic Universe Model says that the energy in the form of electromagnetic radiation passing grazingly near any gravitating mass changes in frequency and finally will convert into neutrinos (mass). Hence Dynamic Universe Model proposes another process where energy will be converted back into matter and the cycle energy to mass to energy continues, sustaining the Universe to maintain this present status for ever in this form something like a Steady state model without any expansion. This we will see in Part 2: Energy - Mass - Energy Cycle. After converting energy into mass “how various elements are formed and where they are formed?” will be next logical question. Dynamic Universe Model says that these various particles change into higher massive particles or may get bombarded into stars or planets and various elements are formed. Here we bifurcate the formation of elements into 6 processes. They are for Elementary particles and elements generated in frequency changing process, By Cosmic rays, By Small stars, By Large Stars, By Super Novae and Manmade elements By Neutron Stars. This we will discuss in Part 3: Nucleosynthesis.展开更多
Posttraumatic stress disorder(PTSD) is a common anxiety disorder characterised by its persistence of symptoms after a traumatic experience. Although some patients can be cured, many do not benefit enough from the psyc...Posttraumatic stress disorder(PTSD) is a common anxiety disorder characterised by its persistence of symptoms after a traumatic experience. Although some patients can be cured, many do not benefit enough from the psychological therapies or medication strategies used. Many researchers use animal models to learn more about the disorder and several models are available. The most-used physical stressor models are single-prolonged stress, restraint stress, foot shock, stress-enhanced fear learning, and underwater trauma. Common social stressors are housing instability, social instability, earlylife stress, and social defeat. Psychological models are not as diverse and rely on controlled exposure to the test animal's natural predator. While validation of these models has been resolved with replicated symptoms using analogous stressors, translating new findings to human patients remains essential for their impact on the field. Choosing a model to experiment with can be challenging; this overview of what is possible with individual models may aid in making a decision.展开更多
The overview shows that the scientific interest in social behaviour in mice has exponentially grown in the last two decades in parallel with advances in biotechnology and the emergence of genetically engineered mice. ...The overview shows that the scientific interest in social behaviour in mice has exponentially grown in the last two decades in parallel with advances in biotechnology and the emergence of genetically engineered mice. Most of the studies are psychopharmacological or look for the neurochemical bases of social behaviour and its alterations. However, the rol of social behaviour per se is increasing mainly in those research works aimed to model neuropsychiatric and neurode-generative diseases. In fact, at the translational level, the study of social behaviour in murine models is relevant because changes in social behaviour are present in most neuropsychiatric and neurodegenerative disorders as well as in other diseases that, directly or indirectly, affect the sphere of social relationships. The consideration of social behaviour in the experimental design of basic and translational research works using murine models may improve the predictive validity of new preventive and/or therapeutic strategies. The present work provides conceptual description of social behaviour in mice, the tests used to measure it and analyzes its increasing interest, mostly in the area of neuroscience. It reviews the 821 scientific studies (in English) included in the MEDLINE database from 1930 to December 2012. Keywords used for the search where those related to the different kinds of social behaviour (spontaneous or induced) in mice and took into account the diversity of experimental paradigms (dyads, groups, parental relationships, isolation) and the wide spectrum of behavioural tests available.展开更多
Major depressive disorder(MDD)has been a devastating neurological problem in modern history.However,therapeutic strategies to relief the disease are inadequate.The limit in understanding of the molecular mechanism of ...Major depressive disorder(MDD)has been a devastating neurological problem in modern history.However,therapeutic strategies to relief the disease are inadequate.The limit in understanding of the molecular mechanism of MDD has been holding back discovery of new therapies.Behind this problem is the establishment of animal models to truly reflect human MDD pathology.In this review,we discuss our current understanding of the molecular mechanism of MDD and the strength and weakness of rodent models of depression.Developing new models of MDD and finding new drugable targets are still important steps to discover new therapies against MDD.展开更多
Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is r...Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.展开更多
Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the i...Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.展开更多
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
文摘Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
文摘This manuscript provides a comparison of the Hypersphere World-Universe Model (WUM) with the prevailing Big Bang Model (BBM) of the Standard Cosmology. The performed analysis of BBM shows that the Four Pillars of the Standard Cosmology are model-dependent and not strong enough to support the model. The angular momentum problem is one of the most critical problems in BBM. Standard Cosmology cannot explain how Galaxies and Extra Solar systems obtained their substantial orbital and rotational angular momenta, and why the orbital momentum of Jupiter is considerably larger than the rotational momentum of the Sun. WUM is the only cosmological model in existence that is consistent with the Law of Conservation of Angular Momentum. To be consistent with this Fundamental Law, WUM discusses in detail the Beginning of the World. The Model introduces Dark Epoch (spanning from the Beginning of the World for 0.4 billion years) when only Dark Matter Particles (DMPs) existed, and Luminous Epoch (ever since for 13.8 billion years). Big Bang discussed in Standard Cosmology is, in our view, transition from Dark Epoch to Luminous Epoch due to Rotational Fission of Overspinning Dark Matter (DM) Supercluster’s Cores. WUM envisions Matter carried from the Universe into the World from the fourth spatial dimension by DMPs. Ordinary Matter is a byproduct of DM annihilation. WUM solves a number of physical problems in contemporary Cosmology and Astrophysics through DMPs and their interactions: Angular Momentum problem in birth and subsequent evolution of Galaxies and Extrasolar systems—how do they obtain it;Fermi Bubbles—two large structures in gamma-rays and X-rays above and below Galactic center;Diversity of Gravitationally-Rounded Objects in Solar system;some problems in Solar and Geophysics [1]. WUM reveals Inter-Connectivity of Primary Cosmological Parameters and calculates their values, which are in good agreement with the latest results of their measurements.
文摘The aim of this work is mathematical education through the knowledge system and mathematical modeling. A net model of formation of mathematical knowledge as a deductive theory is suggested here. Within this model the formation of deductive theory is represented as the development of a certain informational space, the elements of which are structured in the form of the orientated semantic net. This net is properly metrized and characterized by a certain system of coverings. It allows injecting net optimization parameters, regulating qualitative aspects of knowledge system under consideration. To regulate the creative processes of the formation and realization of mathematical know- edge, stochastic model of formation deductive theory is suggested here in the form of branching Markovian process, which is realized in the corresponding informational space as a semantic net. According to this stochastic model we can get correct foundation of criterion of optimization creative processes that leads to “great main points” strategy (GMP-strategy) in the process of realization of the effective control in the research work in the sphere of mathematics and its applications.
基金supported by the National Natural Science Foundation of China,No.81501051(to JR),81572127(to JL)the Scientific Research Project of Huashan Hospital of Fudan University of China,No.2013QD05(to JR)
文摘Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic(phrenic nerve group), intercostal(intercostal nerve group) or thoracodorsal nerves(thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201+2 种基金the National Natural Science Foundation of China,No.31271284,31171150,81171146,30971526,31040043,31371210,81372044,31471144Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270the Natural Science Foundation of Beijing of China,No.7142164
文摘Previous animal studies of cauda equina injury have primarily used rat models, which display significant differences from humans. Furthermore, most studies have focused on electrophysio- logical examination. To better mimic the outcome after surgical repair of cauda equina injury, a novel animal model was established in the goat. Electrophysiological, histological and magnetic resonance imaging methods were used to evaluate the morphological and functional outcome after cauda equina injury and end-to-end suture. Our results demonstrate successful establish- ment of the goat experimental model of cauda equina injury. This novel model can provide detailed information on the nerve regenerative process following surgical repair of cauda equina injury.
基金supported by the Auckland Medical Research Foundation,No.1117017(to CPU)
文摘Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.
文摘The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
文摘The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.
文摘Alzheimer’s disease is one of the most frequent neurodegenerative diseases.This pathology is characterized by protein aggregates,mainly constituted by amyloid peptide and tau,leading to neuronal death and cognitive impairments.Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies.However,stilbenes presenting multiple pharmacological effects could be good potential therapeutic candidates.The aim of this review is to gather the more significant papers among the broad literature on this topic,concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer’s disease.Indeed,numerous studies focus on cellular models,but an in vivo approach remains of primary importance since in animals (mice or rats,generally),bioavailability and metabolism are taken into account,which is not the case in in vitro studies.Furthermore,examination of memory ability is feasible in animal models,which strengthens the relevance of a compound with a view to future therapy in humans.This paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in humans.This review shows that resveratrol,the reference polyphenol,is largely studied and seems to have interesting properties on amyloid plaques,and cognitive impairment.However,some resveratrol derivatives such as gnetin C,trans-piceid,or astringin have never been tested on animals.Furthermore,pterostilbene is of particular interest,by its improvement of cognitive disorders and its neuroprotective role.It could be relevant to evaluate this molecule in clinical trials.
文摘Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.
文摘Objective:Peripheral nerve repair is required after traumatic injury.This common condition represents a major public health problem worldwide.Recovery after nerve repair depends on several factors,including the severity of the injury,the nerve involved,and the surgeon’s technical skills.Despite the precise microsurgical repair of nerve lesions,adequate functional recovery is not always achieved and,therefore,the regeneration process and surgical techniques are still being studied.Pre-clinical animal models are essential for this research and,for this reason,the focus of the present systematic review(according to the PRISMA statement)was to analyze the different animal models used in pre-clinical peripheral nerve repair studies.Data sources:Original articles,published in English from 2000 to 2018,were collected using the Web of Science,Scopus,and PubMed databases.Data selection:Only preclinical trials on direct nerve repair were included in this review.The articles were evaluated by the first two authors,in accordance with predefined data fields.Outcome measures:The primary outcomes included functional motor abilities,daily activity and regeneration rate.Secondary outcomes included coaptation technique and animal model.Results:This review yielded 267 articles,of which,after completion of the screening,49 studies were analyzed.There were 1425 animals in those 49 studies,being rats,mice,guinea pigs,rabbits,cats and dogs the different pre-clinical models.The nerves used were classified into three groups:head and neck(11),forelimb(8)and hindlimb(30).The techniques used to perform the coaptation were:microsuture(46),glue(12),laser(8)and mechanical(2).The follow-up examinations were histology(43),electrophysiological analysis(24)and behavioral observation(22).Conclusion:The most widely used animal model in the study of peripheral nerve repair is the rat.Other animal models are also used but the cost-benefit of the rat model provides several strengths over the others.Suture techniques are currently the first option for nerve repair,but the use of glues,lasers and bioengineering materials is increasing.Hence,further research in this field is required to improve clinical practice.
基金National Key Research and Development Project of China,Grant/Award Number:2016YFD0500304CAMS Innovation Fund for Medical Sciences,Grant/Award Number:NO.2016-I2M-1-014\2016-12M-006the Chinese National Major S&T Project,Grant/Award Number:NO.2017ZX10304402-001-003
文摘In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.
文摘In this paper we will see the model of Universe according to Dynamic Universe Model of Cosmology by visualizing various processes that are happening in the Universe as per experimental evidences. For simplifying the matter here, we will see in part 1: about the Galaxy life cycle, where the birth and death of Galaxies discussed. Probably Universe gives guidance for the movement of Galaxies. We call this Part 1: Thinking and Reproducing Universe or Mindless Universe? (Galaxy life cycle). We see every day Sun, Stars, Galaxies etc., dissipating enormous energy in the form of radiation by the way of fusion of Hydrogen to helium. So after sometime all the Hydrogen is spent and Universe will die, is it not? … Dynamic Universe Model says that the energy in the form of electromagnetic radiation passing grazingly near any gravitating mass changes in frequency and finally will convert into neutrinos (mass). Hence Dynamic Universe Model proposes another process where energy will be converted back into matter and the cycle energy to mass to energy continues, sustaining the Universe to maintain this present status for ever in this form something like a Steady state model without any expansion. This we will see in Part 2: Energy - Mass - Energy Cycle. After converting energy into mass “how various elements are formed and where they are formed?” will be next logical question. Dynamic Universe Model says that these various particles change into higher massive particles or may get bombarded into stars or planets and various elements are formed. Here we bifurcate the formation of elements into 6 processes. They are for Elementary particles and elements generated in frequency changing process, By Cosmic rays, By Small stars, By Large Stars, By Super Novae and Manmade elements By Neutron Stars. This we will discuss in Part 3: Nucleosynthesis.
基金The Netherlands Organisation for Scientific Research(NWO),No.864.10.003(awarded to Judith R Homberg)
文摘Posttraumatic stress disorder(PTSD) is a common anxiety disorder characterised by its persistence of symptoms after a traumatic experience. Although some patients can be cured, many do not benefit enough from the psychological therapies or medication strategies used. Many researchers use animal models to learn more about the disorder and several models are available. The most-used physical stressor models are single-prolonged stress, restraint stress, foot shock, stress-enhanced fear learning, and underwater trauma. Common social stressors are housing instability, social instability, earlylife stress, and social defeat. Psychological models are not as diverse and rely on controlled exposure to the test animal's natural predator. While validation of these models has been resolved with replicated symptoms using analogous stressors, translating new findings to human patients remains essential for their impact on the field. Choosing a model to experiment with can be challenging; this overview of what is possible with individual models may aid in making a decision.
文摘The overview shows that the scientific interest in social behaviour in mice has exponentially grown in the last two decades in parallel with advances in biotechnology and the emergence of genetically engineered mice. Most of the studies are psychopharmacological or look for the neurochemical bases of social behaviour and its alterations. However, the rol of social behaviour per se is increasing mainly in those research works aimed to model neuropsychiatric and neurode-generative diseases. In fact, at the translational level, the study of social behaviour in murine models is relevant because changes in social behaviour are present in most neuropsychiatric and neurodegenerative disorders as well as in other diseases that, directly or indirectly, affect the sphere of social relationships. The consideration of social behaviour in the experimental design of basic and translational research works using murine models may improve the predictive validity of new preventive and/or therapeutic strategies. The present work provides conceptual description of social behaviour in mice, the tests used to measure it and analyzes its increasing interest, mostly in the area of neuroscience. It reviews the 821 scientific studies (in English) included in the MEDLINE database from 1930 to December 2012. Keywords used for the search where those related to the different kinds of social behaviour (spontaneous or induced) in mice and took into account the diversity of experimental paradigms (dyads, groups, parental relationships, isolation) and the wide spectrum of behavioural tests available.
文摘Major depressive disorder(MDD)has been a devastating neurological problem in modern history.However,therapeutic strategies to relief the disease are inadequate.The limit in understanding of the molecular mechanism of MDD has been holding back discovery of new therapies.Behind this problem is the establishment of animal models to truly reflect human MDD pathology.In this review,we discuss our current understanding of the molecular mechanism of MDD and the strength and weakness of rodent models of depression.Developing new models of MDD and finding new drugable targets are still important steps to discover new therapies against MDD.
文摘Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.
基金supported by the National Natural Science Foundation of China,No.81772421(to YH).
文摘Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.
