RESUMO
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.
Assuntos
Lipoproteínas LDL , Microglia , Neuromielite Óptica , Neuromielite Óptica/sangue , Neuromielite Óptica/patologia , Neuromielite Óptica/metabolismo , Microglia/metabolismo , Animais , Camundongos , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Humanos , Feminino , Masculino , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/metabolismo , Adulto , Pessoa de Meia-Idade , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Bainha de Mielina/metabolismo , Bainha de Mielina/patologiaRESUMO
Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating diseases of the central nervous system, have drawn the attention of many researchers due to the relapsing courses and cumulative disability. A first bibliometric analysis of NMOSD was conducted to identify the research hotspots and emerging trends. Articles relevant to NMOSD published in the core collection of Web of Science were retrieved and analyzed through visualized analysis using CiteSpace and VOSviewer, focusing on annual publication trends, countries, institutions, authors, journals, and keywords. The analysis showed that over the past 30 years, publications related to NMOSD had shown steady growth with slight fluctuations. The United States played an important part in this field, with the highest outputs and the greatest number of citations. Research hotspots of NMOSD had gradually shifted from the definition, biomarkers, and diagnostic criteria to diagnosis and treatment, particularly immunotherapy. This bibliometric analysis provides researchers with a theoretical basis for studying NMOSD and offers guidance for future research directions.
RESUMO
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.
Assuntos
Glicoproteínas de Membrana , Microglia , Neuromielite Óptica , Receptores Imunológicos , Animais , Camundongos , Sistema Nervoso Central , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microglia/metabolismo , Bainha de Mielina/metabolismo , Neuromielite Óptica/metabolismo , Fagocitose/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismoRESUMO
OBJECTIVE: To build the colony immune defence and to control the periodic epidemics of hepatitis A after a mass vaccination of live attenuated hepatitis A vaccine. METHODS: Through yearly observing the correlation of the accumulative inoculation rates of live attenuated hepatitis A vaccine, the crowd immune standard and the morbidity of hepatitis A after administered live attenuated hepatitis A vaccine among susceptible population and surveilling anti-HAV IgG in the different epidemic areas. RESULTS: (1) The accumulative inoculation rates of live attenuated hepatitis A vaccine was 34.15% in 8 years from 1993 to 2000, among which they were 84.46%, 82.23% and 15.14% in the preschool children, primary and middle school student and 15 - 45 age groups respectively. The morbidity of hepatitis A decreased to 8.26/100,000 in 2000. (2) The crowd positive rates of anti-HAV IgG were 74.24% in 1998 and 83.68% by 2000. Among which they were 74.02%, 68.49%, 79.41%, 85.71% and 90.80% in 2 - 4, 6 - 8, 13 - 15, 20- and 30 - 39 age groups respectively. (3) The accumulative inoculation rates were 37.36%, 51.08% and 28.68% in the inspection areas of Tongtai, Binhai and Yandu respectively. The crowd positive rates of anti-HAV IgG in three inspect area were 85.71%, 85.94% and 78.63% respectively. It was noticed the correlation between the accumulative inoculation rates and the crowd positive rates of anti-HAV IgG was (r(city) = 0.91, F = 15.10, P < 0.03). CONCLUSION: The results showed that the crowd positive rates of anti-HAV IgG had increased to 85% while, the colony immune defence of hepatitis A was effectively built to break the periodic epidemics of hepatitis A. The morbidity of hepatitis A decreased to the lowest level in the history.