Selective role of Na+/H+exchanger inCx3cr1+microglial activation, white matter demyelination, and post‐stroke function recovery
| العنوان: | Selective role of Na+/H+exchanger inCx3cr1+microglial activation, white matter demyelination, and post‐stroke function recovery |
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| المؤلفون: | T. Kevin Hitchens, Gulnaz Begum, Wen Zhu, Victoria M. Pigott, Lesley M. Foley, Abhishek Mishra, Yejie Shi, Shanshan Song, Tong Jiang, Shaoxia Wang, Rachana Nayak, Dandan Sun, Karen E. Carney, Gary E. Shull |
| المصدر: | Glia. 66:2279-2298 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, CX3C Chemokine Receptor 1, Mice, Transgenic, Nerve Tissue Proteins, Inflammation, Article, White matter, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, CX3CR1, medicine, Animals, Neuroinflammation, 110999 Neurosciences not elsewhere classified, Sodium-Hydrogen Exchanger 1, biology, Microglia, CD68, Macrophages, FOS: Clinical medicine, Calcium-Binding Proteins, Microfilament Proteins, Brain, Infarction, Middle Cerebral Artery, Recovery of Function, White Matter, Hyperintensity, Mice, Inbred C57BL, Disease Models, Animal, Tamoxifen, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Neurology, Integrin alpha M, Somatosensory Disorders, biology.protein, Female, medicine.symptom, 030217 neurology & neurosurgery, Demyelinating Diseases |
| الوصف: | p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 8.0px Helvetica; color: #2f2a2b} span.s1 {font: 5.5px Helvetica} Na1/H1 exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1-CreER;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)- treated mice at 48 hr and 14 days post-stroke. However, the Tam-treated mice showed significantly higher survival rate and faster neurological function recovery during day 1–14 post-stroke. Deletion of microglial Nhe1 prevented the elevation of CD11b1/CD45low-med microglia in the ischemic hemisphere at day 3 post-stroke, but stimulated expression of Ym1, CD68, TGF-b, IL-10, decreased expression of CD86 and IL-1b, and reduced GFAP1 reactive astrocytes. Moreover, at day 14 post-stroke, enhanced white matter myelination was detected in the microglial Nhe1 deleted mice. In comparison, neuronal Nhe1-null mice (the CamKII-Cre1/2;Nhe1f/f mice) showed a significant reduction in both acute and subacute infarct volume, along with increased survival rate and moderate neurological function recovery. However, these neuronal Nhe1-null mice did not exhibit reduced activation of CD11b1/CD45low-med microglia or CD11b1/CD45hi macrophages in the ischemic brains, and they exhibited no reductions in white matter lesions. Taken together, this study demonstrated that deletion of microglial and neuronal Nhe1 had differential effects on ischemic brain damage. Microglial NHE1 is involved in pro-inflammatory responses during post-stroke brain tissue repair. In contrast, neuronal NHE1 activation is directly associated with the acute ischemic neuronal injury but not inflammation. Our study reveals that NHE1 protein is a potential therapeutic target critical for differential regulation of ischemic neuronal injury, demyelination and tissue repair. |
| تدمد: | 1098-1136 0894-1491 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec240635431314f5f40739c333db0308 https://doi.org/10.1002/glia.23456 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ec240635431314f5f40739c333db0308 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981136 08941491 |
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