Roscovitine Attenuates Microglia Activation and Monocyte Infiltration via p38 MAPK Inhibition in the Rat Frontoparietal Cortex Following Status Epilepticus
| العنوان: | Roscovitine Attenuates Microglia Activation and Monocyte Infiltration via p38 MAPK Inhibition in the Rat Frontoparietal Cortex Following Status Epilepticus |
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| المؤلفون: | Seo-Hyeon Choi, Ji-Eun Kim, Min-Jeong Kong, Tae-Cheon Kang, Hana Park |
| المصدر: | Cells Volume 8 Issue 7 Cells, Vol 8, Iss 7, p 746 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, CCR2, animal diseases, p38 mitogen-activated protein kinases, seizure, LAMP1, p38 Mitogen-Activated Protein Kinases, Monocytes, Article, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Status Epilepticus, medicine, Roscovitine, Animals, Protein kinase A, lcsh:QH301-705.5, CD68, Neuroinflammation, Chemokine CCL2, Microglia, Iba-1, Chemistry, Kinase, Cyclin-dependent kinase 5, Monocyte, Lysosome-Associated Membrane Glycoproteins, General Medicine, biochemical phenomena, metabolism, and nutrition, Cell biology, Frontal Lobe, Rats, SB202190, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), nervous system, Blood-Brain Barrier, IB4, epilepsy, 030217 neurology & neurosurgery, NFκB |
| الوصف: | Under physiological conditions, microglia are unique immune cells resident in the brain that is isolated from the systemic immune system by brain-blood barrier. Following status epilepticus (SE, a prolonged seizure activity), microglia are rapidly activated and blood-derived monocytes that infiltrate the brain therefore, the regulations of microglia activation and monocyte infiltration are one of the primary therapeutic strategies for inhibition of undesirable consequences from SE. Roscovitine, a potent (but not selective) cyclin-dependent kinase 5 (CDK5) inhibitor, has been found to exert anti-inflammatory and microglia-inhibiting actions in several in vivo models, although the underlying mechanisms have not been clarified. In the present study, roscovitine attenuated SE-induces monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC), accompanied by reducing expressions of monocyte chemotactic protein-1 (MCP-1) and lysosome-associated membrane protein 1 (LAMP1) in resident microglia, while it did not affect microglia transformation to amoeboid form. Furthermore, roscovitine ameliorated the up-regulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, but not nuclear factor-κB-S276 phosphorylation. Similar to roscovitine, SB202190, a p38 MAPK inhibitor, mitigated monocyte infiltration and microglial expressions of MCP-1 and LAMP1 in the FPC following SE. Therefore, these findings suggest for the first time that roscovitine may inhibit SE-induced neuroinflammation via regulating p38 MAPK-mediated microglial responses. |
| وصف الملف: | application/pdf |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5572531333ed44bd3639f683be60d90fTest https://pubmed.ncbi.nlm.nih.gov/31331032Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5572531333ed44bd3639f683be60d90f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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