Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation
Open accessAbstract
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 alpha (TNFalpha) levels. Central antagonism of TNFalpha 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 TNFalpha 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 TNFalpha-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation.
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Increased intestinal inflammation driven by either LPS or bacterial infection correlates with elevated levels of microglial activation and release of pro-inflammatory cytokines.
“Indeed, increased intestinal inflammation driven by either LPS or bacterial infection correlates with elevated levels of microglial activation and release of pro-inflammatory cytokines (Riazi et al., 2008; Henry et al., 2009).”
From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Riazi et al., 2008
Increased circulation of BBB-permeable pro-inflammatory cytokines and neurotoxic compounds may contribute to heightened microglial activation and production of pro-inflammatory cytokines in the brain.
“Increased circulation of BBB-permeable pro-inflammatory cytokines and neurotoxic compounds may contribute to heightened microglial activation and production of pro-inflammatory cytokines in the brain (Qin et al., 2008; Riazi et al., 2008).”
From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Riazi et al., 2008
Cites
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · see citing works
Hapten-Induced Model of Chronic Inflammation and Ulceration in the Rat Colon
Morris, G. P., Beck, P. L., Herridge, M. S., Depew, W. T., Szewczuk, M. R., & Wallace, J. L. (1989) · Gastroenterology · doi:10.1016/s0016-5085(89)80079-4 · Cited by 1,832 · see citing works
Synaptic scaling mediated by glial TNF-α
Stellwagen, D., & Malenka, R. C. (2006) · Nature · doi:10.1038/nature04671 · Cited by 1,715 · see citing works
Brain Inflammation in Epilepsy: Experimental and Clinical Evidence
Vezzani, A., & Granata, T. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00298.x · Cited by 1,038 · see citing works
Differential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α
Stellwagen, D., Beattie, E. C., Seo, J. Y., & Malenka, R. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4486-04.2005 · Cited by 985 · cited 1× · see citing works
“TNF can independently enhance excitatory synaptic strength by increasing membrane trafficking of AMPA receptors in cultured hippocampal pyramidal neurons (2) and reduce the overall inhibitory currents mediated through GABAA receptors in vitro (2, 5).”
BackgroundTikka, T., Fiebich, B. L., Goldsteins, G., Keinänen, R., & Koistinaho, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02580.2001 · Cited by 958 · see citing works
Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity
Dantzer, R. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.07.040 · Cited by 743 · see citing works
Vezzani, A., Conti, M., Luigi, A. D., Ravizza, T., Moneta, D., Marchesi, F., & Simoni, M. D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-12-05054.1999 · Cited by 603 · see citing works
Mechanisms of inflammatory pain
Kidd, B. L., & Urbán, L. (2001) · British Journal of Anaesthesia · doi:10.1093/bja/87.1.3 · Cited by 595 · see citing works
The role of cytokines in the pathophysiology of epilepsy
Vezzani, A., Balosso, S., & Ravizza, T. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.03.009 · Cited by 558 · see citing works
“Inflammatory” Cytokines: Neuromodulators in Normal Brain?
Vitkovic, L., Bockaert, J., & Jacque, C. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740457.x · Cited by 506 · see citing works
Vezzani, A., Moneta, D., Conti, M., Richichi, C., Ravizza, T., Luigi, A. D., Simoni, M. D., Sperk, G., Andell-Jonsson, S., Lundkvist, J., et al. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.190206797 · Cited by 477 · see citing works
Molecular insights on the cerebral innate immune system
Rivest, S. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00055-7 · Cited by 417 · see citing works
Löscher, W., Hönack, D., Fassbender, C. P., & Nolting, B. (1991) · Epilepsy Research · doi:10.1016/0920-1211(91)90062-k · Cited by 403 · see citing works
Chen, J., Buchanan, J. B., Sparkman, N. L., Godbout, J. P., Freund, G. G., & Johnson, R. W. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.014 · Cited by 396 · see citing works
Effects of cytokines and infections on brain neurochemistry
Dunn, A. J. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.04.002 · Cited by 336 · see citing works
Perreault, P., & Avoli, M. (1991) · Journal of Neurophysiology · doi:10.1152/jn.1991.65.4.771 · Cited by 330 · see citing works
Maier, S. F. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(03)00032-1 · Cited by 300 · see citing works
Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats
Galic, M. A., Riazi, K., Heida, J. G., Mouihate, A., Fournier, N. M., Spencer, S. J., Kalynchuk, L. E., Teskey, G. C., & Pittman, Q. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1901-08.2008 · Cited by 283 · see citing works
Self-citationRutecki, P. A., Lebeda, F. J., & Johnston, D. (1987) · Journal of Neurophysiology · doi:10.1152/jn.1987.57.6.1911 · Cited by 277 · see citing works
New Roles for Interleukin-1 Beta in the Mechanisms of Epilepsy
Vezzani, A., & Baram, T. (2007) · Epilepsy Currents · doi:10.1111/j.1535-7511.2007.00165.x · Cited by 266 · see citing works
Somatic Comorbidity of Epilepsy in the General Population in Canada
Téllez‐Zenteno, J. F., Matijevic, S., & Wiebe, S. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00344.x · Cited by 254 · see citing works
Neugebauer, V., Li, W., Bird, G. C., Bhave, G. B., & Gereau, R. W. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00052.2003 · Cited by 249 · see citing works
Turrin, N. P., Gayle, D. A., Ilyin, S. E., Flynn, M. C., Langhans, W., Schwartz, G. J., & Plata‐Saláman, C. R. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00445-2 · Cited by 235 · see citing works
Wang, S., Cheng, Q., Malik, S., & Yang, J. H. (2000) · PubMed · Cited by 232 · see citing works
Carson, M. J. (2002) · Glia · doi:10.1002/glia.10145 · Cited by 227 · see citing works
Effect of cytokines on neuronal excitability
Schäfers, M., & Sorkin, L. S. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.03.052 · Cited by 224 · see citing works
Tumor necrosis factor‐α inhibits seizures in mice via p75 receptors
Balosso, S., Ravizza, T., Perego, C., Peschon, J. J., Campbell, I. L., Simoni, M. G. D., & Vezzani, A. (2005) · Annals of Neurology · doi:10.1002/ana.20480 · Cited by 209 · see citing works
Cui, Y., Liao, X., Liu, W., Guo, R., Wu, Z.-Z., Zhao, C., Chen, P., & Feng, J. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.07.014 · Cited by 207 · see citing works
Tomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203 · see citing works
Causal Links between Brain Cytokines and Experimental Febrile Convulsions in the Rat
Heida, J. G., & Pittman, Q. J. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00294.x · Cited by 202 · see citing works
Self-citationNeurath, M. F., Fuss, I. J., & Strober, W. (2000) · International Reviews of Immunology · doi:10.3109/08830180009048389 · Cited by 192 · see citing works
van Dam, A., Bauer, J., Tilders, F. J. H., & BERKENBOSCH, F. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00549-k · Cited by 190 · see citing works
Mandhane, S. N., Aavula, K., & Rajamannar, T. (2007) · Seizure · doi:10.1016/j.seizure.2007.05.005 · Cited by 179 · see citing works
Lestage, J., Verrier, D., Palin, K., & Dantzer, R. (2002) · Brain, Behavior, and Immunity · doi:10.1016/s0889-1591(02)00014-4 · Cited by 170 · see citing works
Brain-derived TNFα mediates neuropathic pain
Ignatowski, T. A., Covey, W. C., Knight, P. R., Severin, C. M., Nickola, T. J., & Spengler, R. N. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01782-5 · Cited by 167 · see citing works
Sayyah, M., Javadpour, M., & Ghazi‐Khansari, M. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.043 · Cited by 164 · see citing works
Beneficial effects of local or systemic lidocaine in experimental colitis
McCafferty, D., Sharkey, K. A., & Wallace, J. L. (1994) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1994.266.4.g560 · Cited by 132 · see citing works
Self-citationHarré, E. ‐., Galic, M. A., Mouihate, A., Noorbakhsh, F., & Pittman, Q. J. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06031.x · Cited by 130 · see citing works
Self-citationThe protective effect of the vagus nerve in a murine model of chronic relapsing colitis
Ghia, J., Blennerhassett, P. A., El–Sharkawy, R. T., & Collins, S. M. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00240.2007 · Cited by 123 · see citing works
Anticonvulsant properties of hypothermia in experimental status epilepticus
Schmitt, F. C., Buchheim, K., Meierkord, H., & Holtkamp, M. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.05.008 · Cited by 115 · see citing works
Neurologic manifestations of ulcerative colitis
Scheid, R., & Teich, N. (2007) · European Journal of Neurology · doi:10.1111/j.1468-1331.2007.01718.x · Cited by 114 · see citing works
Interleukin‐1 System in CNS Stress
Bartfai, T., Sánchez-Alavez, M., Andell, S., Schultzberg, M., Vezzani, A., Danielsson, E., & Conti, B. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1391.022 · Cited by 112 · see citing works
Synaptic plasticity in the amygdala in a visceral pain model in rats
Han, J. S., & Neugebauer, V. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.12.027 · Cited by 110 · see citing works
TNF‐α–secreting monocytes are recruited into the brain of cholestatic mice†‡
Kerfoot, S. M., D’Mello, C., Nguyen, H. H., Ajuebor, M. N., Kubes, P., Le, T. P., & Swain, M. G. (2005) · Hepatology · doi:10.1002/hep.21003 · Cited by 105 · see citing works
Central nervous system recognition of peripheral inflammation: a neural, hormonal collaboration.
Hopkins, S. J. (2007) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 103 · see citing works
Traub, R. D., Bibbig, R., Piechotta, A., Draguhn, R., & Schmitz, D. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.85.3.1246 · Cited by 97 · see citing works
Brückner, C., & Heinemann, U. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02348-3 · Cited by 87 · see citing works
Disruption of the blood–brain barrier during TNBS colitis
Natah, S. S., Mouihate, A., Pittman, Q. J., & Sharkey, K. A. (2005) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2005.00654.x · Cited by 79 · see citing works
Self-citationChronic interleukin‐6 alters the level of synaptic proteins in hippocampus in culture and in vivo
Vereyken, E. J. F., Bajova, H., Chow, S., Graan, P. N. E. D., & Gruol, D. L. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05615.x · Cited by 61 · see citing works
Reynolds, J. L., Ignatowski, T. A., Sud, R., & Spengler, R. N. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.067835 · Cited by 61 · see citing works
Yonekawa, W. D., Kapetanović, I. M., & Kupferberg, H. J. (1995) · Epilepsy Research · doi:10.1016/0920-1211(94)00077-a · Cited by 58 · see citing works
Role of tumor necrosis factor receptors in an animal model of acute colitis
Rojas‐Cartagena, C., Flores, I., & Appleyard, C. B. (2005) · Cytokine · doi:10.1016/j.cyto.2005.08.001 · Cited by 57 · see citing works
Yuhas, Y., Shulman, L. M., Weizman, A., et al. (1999) · Infection and Immunity · doi:10.1128/iai.67.3.1455-1460.1999 · Cited by 55 · see citing works
Protective role of vagal afferents in experimentally-induced colitis in rats
Mazelin, L., Theodorou, V., Moré, J., Fioramonti, J., & Bueno, L. P. (1998) · Journal of the Autonomic Nervous System · doi:10.1016/s0165-1838(98)00113-1 · Cited by 52 · see citing works
Endotoxaemia and cytokine production in experimental colitis
Neilly, P., Gardiner, K. R., Kirk, S., et al. (1995) · British journal of surgery · doi:10.1002/bjs.1800821110 · Cited by 39 · see citing works
Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-α
Spencer, S. J., Hyland, N. P., Sharkey, K. A., & Pittman, Q. J. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00398.2006 · Cited by 28 · see citing works
Self-citationNakai, M., Sudo, K., Yamada, Y., Kojima, Y., Kato, T., Saito, K., Moriwaki, H., & Seishima, M. (2005) · Digestive Diseases and Sciences · doi:10.1007/s10620-005-2913-1 · Cited by 25 · see citing works
Intestinal inflammation alters the susceptibility to pentylenetetrazole‐induced seizure in mice
Riazi, K., Honar, H., Homayoun, H., Demehri, S., Bahadori, M., & Dehpour, A. R. (2004) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2003.03284.x · Cited by 25 · see citing works
Self-citationCentral and peripheral minocycline suppresses motor activity in rats
Kofman, O., van Embden, S., Alpert, C., et al. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90481-8 · Cited by 21 · see citing works
Balter-Seri, J., Yuhas, Y., Weizman, A., et al. (1999) · Infection and Immunity · doi:10.1128/iai.67.12.6364-6368.1999 · Cited by 21 · see citing works
Compromised neuroimmune status in rats with experimental colitis
Boisse, L., Sickle, M. D. V., Sharkey, K. A., & Pittman, Q. J. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.00929.x · Cited by 11 · see citing works
Self-citationCompromised neuroimmune status in rats with experimental colitis
Lomax, L. B., Sickle, M. D. V., Sharkey, K. A., & Pittman, Q. J. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.034546 · Cited by 9 · see citing works
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da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00362 · Cited by 572 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“Indeed, increased intestinal inflammation driven by either LPS or bacterial infection correlates with elevated levels of microglial activation and release of pro-inflammatory cytokines (Riazi et al., 2008; Henry et al., 2009).”
BackgroundSex differences in neuroimmunity and pain
Rosen, S., Ham, B., & Mogil, J. S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23831 · Cited by 318 · see citing works
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Chesnokova, V., Pechnick, R. N., & Wawrowsky, K. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.01.017 · Cited by 299 · see citing works
TNF-alpha-induced microglia activation requires miR-342: Impact on NF-kB signaling and neurotoxicity
Brás, J. P., Bravo, J., Freitas, J., Barbosa, M. A., Santos, S. G., Summavielle, T., & Almeida, M. I. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2626-6 · Cited by 236 · see citing works
Ge, L., Liu, S., Li, S., Yang, J., Hu, G., Xu, C., & Song, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1016578 · Cited by 187 · see citing works
Benson, M. J., Manzanero, S., & Borges, K. (2015) · Epilepsia · doi:10.1111/epi.12960 · Cited by 176 · see citing works
Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease
Craig, C. F., Filippone, R. T., Stavely, R., Bornstein, J. C., Apostolopoulos, V., & Nurgali, K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02354-1 · Cited by 124 · see citing works
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Morris, G., & Maes, M. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-012-9324-8 · Cited by 117 · see citing works
Can we ‘seize’ the gut microbiota to treat epilepsy?
De Caro, C., Iannone, L. F., Citraro, R., Striano, P., De Sarro, G., Constanti, A., Cryan, J. F., & Russo, E. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.002 · Cited by 110 · see citing works
Haj-Mirzaian, A., Amiri, S., Amini-Khoei, H., Hosseini, M.-J., Haj-Mirzaian, A., Momeny, M., Rahimi-Balaei, M., & Dehpour, A. R. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.023 · Cited by 100 · see citing works
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Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jačan, A., & Reichmann, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01613 · Cited by 84 · see citing works
Vermersch, P., Airas, L., Berger, T., Deisenhammer, F., Grigoriadis, N., Hartung, H.-P., Magyari, M., Popescu, V., Pozzilli, C., Pugliatti, M., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1495529 · Cited by 21 · see citing works
de Souza Bernardino, T. C., Teixeira, A. L., Miranda, A. S., Guidine, P. M., Rezende, G., Doretto, M. C., Castro, G. P., Drummond, L., Moraes, M. F. D., Tito, P. A. L., et al. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.04.046 · Cited by 18 · see citing works
- Authors
- Riazi, K., Galic, M. A., Kuzmiski, J. B., Ho, W., Sharkey, K. A., & Pittman, Q. J.
- Affiliations
- University of Calgary (CA)
- Scripps Research Institute (US)
- Corresponding author
- Pittman, Quentin J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-11-04
- Volume
- 105
- Issue
- 44
- Pages
- 17151-17156
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2579393
- OpenAlex
- W2059491535
- Cited by
- 400
- References
- 64
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 22 · 2023: 20 · 2022: 36 · 2021: 39 · 2020: 33 · 2019: 27 · 2018: 15 · 2017: 24 · 2016: 25 · 2015: 33 · 2014: 18 · 2013: 14 · 2012: 24
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation
- Crohn's and Colitis Foundation of Canada
- Fondation pour la Recherche Médicale
- Alberta Heritage Foundation for Medical Research
- Killam Trusts
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- peripheral inflammation, microglial activation, TNF-α, CNS excitability, seizure susceptibility, TNBS-induced colitis, hippocampal excitability, minocycline, neuroinflammation, gut-brain axis, chronic inflammation
- MeSH terms
- Animals, Central Nervous System, Colitis, Hippocampus, Male, Seizures, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha, Cytokines, Rats, Sprague-Dawley, Microglia, Rats
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