Glial-derived Neuroinflammation induced with Amyloid-beta-peptide Plus Fibrinogen Injection in Rat Hippocampus.

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY
James G McLarnon
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Abstract

Introduction: The present study has examined microglial and astrocyte activation in association with neuronal degeneration in an animal model using an injection of amyloid-beta peptide Aβ1-42 (Aβ42) plus fibrinogen into rat hippocampus.

Methods: The combination of stimuli is suggested as a novel and potent perturbation to induce gliosis and the production of glial-derived neurotoxic factors in an animal model exhibiting a leaky BBB (blood-brain barrier). Specifically, Aβ42 + fibrinogen stimulation elevated levels of COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) with a considerable extent of neuronal loss associated with microglia and astrocyte activation.

Results: Treatment of injected rats with the broad spectrum anti-inflammatory agent, minocycline or the iNOS inhibitor, 1400 W inhibited gliosis, reduced levels of COX-2 and iNOS, and demonstrated efficacy for neuroprotection.

Conclusion: The findings suggest the utility of combining amyloid beta peptide plus fibrinogen as a potent and understudied neuroinflammatory stimulus for the induction of glial-derived neurotoxic factors in BBB-compromised AD brain.

淀粉样肽加纤维蛋白原注射诱导大鼠海马胶质源性神经炎症。
本研究通过向大鼠海马注射淀粉样β肽Aβ1-42 (Aβ42)和纤维蛋白原,研究了小胶质细胞和星形胶质细胞的活化与神经元变性的关系。方法:在血脑屏障有渗漏的动物模型中,联合刺激被认为是一种新的和有效的扰动,可以诱导胶质细胞形成和胶质源性神经毒性因子的产生。具体来说,a - β42 +纤维蛋白原刺激提高了COX-2(环氧化酶-2)和iNOS(诱导型一氧化氮合酶)的水平,并在相当程度上导致与小胶质细胞和星形胶质细胞活化相关的神经元损失。结果:给大鼠注射广谱抗炎药米诺环素或iNOS抑制剂1400w,可抑制胶质细胞增生,降低COX-2和iNOS水平,显示出神经保护作用。结论:研究结果表明,淀粉样肽和纤维蛋白原结合作为一种有效的神经炎症刺激,可在血脑屏障受损的AD脑中诱导胶质源性神经毒性因子。
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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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