CoChat
Sign Up
Cited by 842

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures

Maroso, Mattia, Balosso, Silvia, Ravizza, Teresa, Liu, Jaron, Aronica, Eleonora, Iyer, Anand M, Rossetti, Carlo, Molteni, Monica, Casalgrandi, Maura, Manfredi, Angelo A, Bianchi, Marco E, Vezzani, Annamaria·2010·Nature Medicine
DOI 10.1038/nm.2127
Open this paper in CoChat — free account

Abstract

Brain inflammation is a major factor in epilepsy, but the impact of specific inflammatory mediators on neuronal excitability is incompletely understood. Using models of acute and chronic seizures in C57BL/6 mice, we discovered a proconvulsant pathway involving high-mobility group box-1 (HMGB1) release from neurons and glia and its interaction with Toll-like receptor 4 (TLR4), a key receptor of innate immunity. Antagonists of HMGB1 and TLR4 retard seizure precipitation and decrease acute and chronic seizure recurrence. TLR4-defective C3H/HeJ mice are resistant to kainate-induced seizures. The proconvulsant effects of HMGB1, like those of interleukin-1beta (IL-1beta), are partly mediated by ifenprodil-sensitive N-methyl-d-aspartate (NMDA) receptors. Increased expression of HMGB1 and TLR4 in human epileptogenic tissue, like that observed in the mouse model of chronic seizures, suggests a role for the HMGB1-TLR4 axis in human epilepsy. Thus, HMGB1-TLR4 signaling may contribute to generating and perpetuating seizures in humans and might be targeted to attain anticonvulsant effects in epilepsies that are currently resistant to drugs.

Overview

Integrity signals

Registry

Crossref · 10.1038/nm.2127

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 52

  1. Hauser, W.A., Annegers, J.F. & Kurland, L.T. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 34, 453–468 (1993). · DOI
  2. Perucca, E., French, J. & Bialer, M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol. 6, 793–804 (2007). · DOI
  3. Vezzani, A. & Granata, T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46, 1724–1743 (2005). · DOI
  4. Pitkänen, A. & Sutula, T.P. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol. 1, 173–181 (2002). · DOI
  5. Bartfai, T. et al. Interleukin-1 system in CNS stress: seizures, fever and neurotrauma. Ann. NY Acad. Sci. 1113, 173–177 (2007). · DOI
  6. Sheng, J.G., Boop, F.A., Mrak, R.E. & Griffin, W.S. Increased neuronal β-amyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1α immunoreactivity. J. Neurochem. 63, 1872–1879 (1994). · DOI
  7. Crespel, A. et al. Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis. Brain Res. 952, 159–169 (2002). · DOI
  8. Ravizza, T. et al. Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol. Dis. 29, 142–160 (2008). · DOI
  9. Ravizza, T. et al. The IL-1β system in epilepsy-associated malformations of cortical development. Neurobiol. Dis. 24, 128–143 (2006). · DOI · Paper page
  10. Boer, K. et al. Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Res. 78, 7–21 (2008). · DOI
  11. Vezzani, A., Balosso, S. & Ravizza, T. The role of cytokines in the pathophysiology of epilepsy. Brain Behav. Immun. 22, 797–803 (2008). · DOI
  12. Vezzani, A. et al. Interleukin-1β immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures. J. Neurosci. 19, 5054–5065 (1999). · DOI
  13. De Simoni, M.G. et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur. J. Neurosci. 12, 2623–2633 (2000). · DOI
  14. Ravizza, T. et al. Interleukin converting enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production. Neurobiol. Dis. 31, 327–333 (2008). · DOI
  15. Viviani, B. et al. Interleukin-1β enhances NMDA receptor–mediated intracellular calcium increase through activation of the Src family of kinases. J. Neurosci. 23, 8692–8700 (2003). · DOI · Paper page
  16. Balosso, S. et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1β. Brain 131, 3256–3265 (2008). · DOI
  17. Kawai, T. & Akira, S. Signaling to NF-κB by Toll-like receptors. Trends Mol. Med. 13, 460–469 (2007). · DOI
  18. Chakravarty, S. & Herkenham, M. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J. Neurosci. 25, 1788–1796 (2005). · DOI · Paper page
  19. Sayyah, M., Javad-Pour, M. & Ghazi-Khansari, M. The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins. Neuroscience 122, 1073–1080 (2003). · DOI
  20. Galic, M.A. et al. Postnatal inflammation increases seizure susceptibility in adult rats. J. Neurosci. 28, 6904–6913 (2008). · DOI
  21. Bianchi, M.E. & Manfredi, A.A. Immunology. Dangers in and out. Science 323, 1683–1684 (2009). · DOI · Paper page
  22. Müller, S., Ronfani, L. & Bianchi, M.E. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J. Intern. Med. 255, 332–343 (2004). · DOI
  23. Bonaldi, T. et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 22, 5551–5560 (2003). · DOI
  24. Park, J.S. et al. Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 279, 7370–7377 (2004). · DOI
  25. Ravizza, T. et al. Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy. Epilepsia 47, 1160–1168 (2006). · DOI
  26. Vezzani, A. et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc. Natl. Acad. Sci. USA 97, 11534–11539 (2000). · DOI
  27. Riban, V. et al. Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112, 101–111 (2002). · DOI
  28. Bouilleret, V. et al. Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience 89, 717–729 (1999). · DOI
  29. Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088 (1998). · DOI · Paper page
  30. Trisciuoglio, L. & Bianchi, M.E. Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway. PLoS One 4, e6234 (2009). · DOI
  31. Yang, H. et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc. Natl. Acad. Sci. USA 101, 296–301 (2004). · DOI · Paper page
  32. Sitia, G., Iannacone, M., Muller, S., Bianchi, M.E. & Guidotti, L.G. Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice. J. Leukoc. Biol. 81, 100–107 (2007). · DOI
  33. Muhammad, S. et al. The HMGB1 receptor RAGE mediates ischemic brain damage. J. Neurosci. 28, 12023–12031 (2008). · DOI
  34. Kutuzova, G.D., Albrecht, R.M., Erickson, C.M. & Qureshi, N. Diphosphoryl lipid A from Rhodobacter sphaeroides blocks the binding and internalization of lipopolysaccharide in RAW 264.7 cells. J. Immunol. 167, 482–489 (2001). · DOI
  35. Macagno, A. et al. A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. J. Exp. Med. 203, 1481–1492 (2006). · DOI
  36. Chenard, B.L. & Menniti, F.S. Antagonists selective for NMDA receptors containing the NR2B subunit. Curr. Pharm. Des. 5, 381–404 (1999). · DOI
  37. Ebert, U., Wlaz, P. & Loscher, W. Anticonvulsant effects by combined treatment with a glycineB receptor antagonist and a polyamine site antagonist in amygdala-kindled rats. Eur. J. Pharmacol. 322, 179–184 (1997). · DOI
  38. Yourick, D.L., Repasi, R.T., Rittase, W.B., Staten, L.D. & Meyerhoff, J.L. Ifenprodil and arcaine alter amygdala-kindling development. Eur. J. Pharmacol. 371, 147–152 (1999). · DOI
  39. De Sarro, G.B., Bagetta, G., Spagnolo, C. & Nistico, G. Antagonists of N-methyl-d-aspartate receptors block seizures induced by putrescine in the deep prepiriform cortex. Neuropharmacology 32, 43–50 (1993). · DOI
  40. Lee, M.S. & Kim, Y.J. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu. Rev. Biochem. 76, 447–480 (2007). · DOI
  41. Rodgers, K.M. et al. The cortical innate immune response increases local neuronal excitability leading to seizures. Brain 132, 2478–2486 (2009). · DOI
  42. Singh, G., Prabhakar, S. & Modi, M. Central nervous system infections and epilepsy. Epilepsia 49 Suppl 6, 1 (2008). · DOI
  43. Prince, D.A. et al. Epilepsy following cortical injury: cellular and molecular mechanisms as targets for potential prophylaxis. Epilepsia 50 Suppl 2, 30–40 (2009). · DOI
  44. Yu, X.M., Askalan, R., Keil, G.J. II & Salter, M.W. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275, 674–678 (1997). · DOI
  45. Tsung, A. et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J. Exp. Med. 204, 2913–2923 (2007). · DOI
  46. Andrassy, M. et al. High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation 117, 3216–3226 (2008). · DOI
  47. Zhao, M., Ma, H., Suh, M. & Schwartz, T.H. Spatiotemporal dynamics of perfusion and oximetry during ictal discharges in the rat neocortex. J. Neurosci. 29, 2814–2823 (2009). · DOI
  48. Ishida, I. et al. Hypoxia diminishes Toll-like receptor 4 expression through reactive oxygen species generated by mitochondria in endothelial cells. J. Immunol. 169, 2069–2075 (2002). · DOI
  49. Yang, H., Wang, H., Czura, C.J. & Tracey, K.J. HMGB1 as a cytokine and therapeutic target. J. Endotoxin Res. 8, 469–472 (2002). · DOI
  50. Kralic, J.E., Ledergerber, D.A. & Fritschy, J.M. Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures. Eur. J. Neurosci. 22, 1916–1927 (2005). · DOI
  51. Suzuki, F. et al. Glutamate receptor antagonists and benzodiazepine inhibit the progression of granule cell dispersion in a mouse model of mesial temporal lobe epilepsy. Epilepsia 46, 193–202 (2005). · DOI
  52. Paxinos, G. & Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates. (Academic Press, San Diego, 1997).

Cited by

Sorted by citations

See all 842

Metadata

Authors
Maroso, M., Balosso, S., Ravizza, T., Liu, J., Aronica, E., Iyer, A. M., Rossetti, C., Molteni, M., Casalgrandi, M., Manfredi, A. A., Bianchi, M. E., & Vezzani, A.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2010-03-28
Volume
16
Issue
4
Pages
413-419
ISSN
  • 1078-8956
  • 1546-170X
DOI
10.1038/nm.2127
Cited by
842
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review