Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation
| العنوان: | Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation |
|---|---|
| المؤلفون: | Kiarash Riazi, Michael A. Galic, Winnie Ho, Keith A. Sharkey, J. Brent Kuzmiski, Quentin J. Pittman |
| المصدر: | Proceedings of the National Academy of Sciences. 105:17151-17156 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Central Nervous System, Male, medicine.medical_treatment, Central nervous system, Hippocampus, Inflammation, Pharmacology, Hippocampal formation, Biology, Rats, Sprague-Dawley, Seizures, medicine, Animals, Multidisciplinary, Microglia, Seizure threshold, Tumor Necrosis Factor-alpha, Biological Sciences, Colitis, Rats, medicine.anatomical_structure, Cytokine, Trinitrobenzenesulfonic Acid, Immunology, Cytokines, Tumor necrosis factor alpha, medicine.symptom |
| الوصف: | Peripheral inflammation leads to a number of centrally mediated physiological and behavioral changes. The underlying mechanisms and the signaling pathways involved in these phenomena are not yet well understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. We induced inflammation in the gut by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to adult male rats. To examine the excitability of the brain in vivo , we administered pentylenetetrazole (PTZ; a GABAergic antagonist) intravenously to evoke clonic seizures. Rats treated with TNBS showed increased susceptibility to PTZ seizures that was strongly correlated with the severity and progression of intestinal inflammation. In vitro hippocampal slices from inflamed, TNBS-treated rats showed increased spontaneous interictal burst firing following application of 4-aminopyridine, indicating increased intrinsic excitability. The TNBS-treated rats exhibited a marked, reversible inflammatory response within the hippocampus, characterized by microglial activation and increases in tumor necrosis factor α (TNFα) levels. Central antagonism of TNFα using a monoclonal antibody or inhibition of microglial activation by i.c.v. injection of minocycline prevented the increase in seizure susceptibility. Moreover, i.c.v. infusion of TNFα in untreated rats for 4 days also increased seizure susceptibility and thus mimicked the changes in seizure threshold observed with intestinal inflammation. Our finding of a microglia-dependent TNFα-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c40b08202e2b7bfb5b107689bc9fad70Test https://doi.org/10.1073/pnas.0806682105Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c40b08202e2b7bfb5b107689bc9fad70 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
|---|