Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus

Authors: Ji-Eun Kim, Hea Jin Ryu, Soo Young Choi, Tae-Cheon Kang

Published in: Journal of Neuroinflammation | Issue 1/2012

Login to get access

Abstract

Background

Status epilepticus (SE) induces severe vasogenic edema in the piriform cortex (PC) accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF)-α in blood-brain barrier (BBB) disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE.

Methods

SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R) prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunits.

Results

Following SE, most activated microglia showed strong TNF-α immunoreactivity. In addition, TNF p75 receptor expression was detected in endothelial cells as well as astrocytes. In addition, only p65-Thr435 phosphorylation was increased in endothelial cells accompanied by SMI-71 expression (an endothelial barrier antigen). Neutralization of TNF-α by soluble TNF p55 receptor (sTNFp55R) infusion attenuated SE-induced vasogenic edema and neuronal damages via inhibition of p65-Thr435 phosphorylation in endothelial cells. Furthermore, sTNFp55R infusion reduced SE-induced neutrophil infiltration in the PC.

Conclusion

These findings suggest that impairments of endothelial cell functions via TNF-α-mediated p65-Thr 485 NF-κB phosphorylation may be involved in SE-induced vasogenic edema. Subsequently, vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss.
Literature
1.
DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG: Epidemiology of status epilepticus. J Clin Neurophysiol 1995, 12:316–325.CrossRefPubMed
2.
Rice AC, DeLorenzo RJ: NMDA receptor activation during status epilepticus is required for the development of epilepsy. Brain Res 1998, 782:240–247.CrossRefPubMed
3.
Stewart LS, Persinger MA: Ketamine Prevents Learning Impairment When Administered Immediately after Status Epilepticus Onset. Epilepsy Behav 2001, 2:585–591.CrossRefPubMed
4.
Gale K: Subcortical structures and pathways involved in convulsive seizure generation. J Clin Neurophysiol 1992, 9:264–277.CrossRefPubMed
5.
Sheen SH, Kim JE, Ryu HJ, Yang Y, Choi KC, Kang TC: Decrease in dystrophin expression prior to disruption of brain-blood barrier within the rat piriform cortex following status epilepticus. Brain Res 2010, 1369:173–183.CrossRefPubMed
6.
Turski L, Ikonomidou C, Turski WA, Bortolotto ZA, Cavalheiro EA: Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse 1989, 3:154–171.CrossRefPubMed
7.
Jo SM, Ryu HJ, Kim JE, Yeo SI, Kim MJ, Choi HC, Song HK, Kang TC: Up-regulation of endothelial endothelin-1 expression prior to vasogenic edema formation in the rat piriform cortex following status epilepticus. Neurosci Lett 2011, 501:25–30.CrossRefPubMed
8.
Kim JE, Yeo SI, Ryu HJ, Kim MJ, Kim DS, Jo SM, Kang TC: Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus. J Comp Neurol 2010, 518:4612–4628.CrossRefPubMed
9.
10.
Nitsch C, Hubauer H: Distant blood-brain barrier opening in subfields of the rat hippocampus after intrastriatal injections of kainic acid but not ibotenic acid. Neurosci Lett 1986, 64:53–58.CrossRefPubMed
11.
Ates N, van Luijtelaar EL, Drinkenburg WH, Vossen JM, Coenen AM: Effects of loreclezole on epileptic activity and on EEG and behaviour in rats with absence seizures. Epilepsy Res 1992, 13:43–48.CrossRefPubMed
12.
Nitsch C, Suzuki R, Fujiwara K, Klatzo I: Incongruence of regional cerebral blood flow increase and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid. J Neurol Sci 1985, 67:67–79.CrossRefPubMed
13.
Cornford EM, Oldendorf WH: Epilepsy and the blood-brain barrier. Adv Neurol 1986, 44:787–812.PubMed
14.
Rodgers KM, Hutchinson MR, Northcutt A, Maier SF, Watkins LR, Barth DS: The cortical innate immune response increases local neuronal excitability leading to seizures. Brain 2009, 132:2478–2486.CrossRefPubMedPubMedCentral
15.
Deli MA, Abrahám CS, Kataoka Y, Niwa M: Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol 2005, 25:59–127.CrossRefPubMed
16.
Sztriha L, Joó F, Szerdahelyi P, Eck E, Koltai M: Effects of dexamethasone on brain edema induced by kainic acid seizures. Neuroscience 1986, 17:107–114.CrossRefPubMed
17.
Sriram K, O'Callaghan JP: Divergent roles for tumor necrosis factor-alpha in the brain. J Neuroimmune Pharmaco 2007, 2:140–153.CrossRef
18.
Kim JE, Ryu HJ, Kang TC: P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus. J Neuroinflammation 2011, 8:62.CrossRefPubMedPubMedCentral
19.
Fotin-Mleczek M, Henkler F, Samel D, Reichwein M, Hausser A, Parmryd I, Scheurich P, Schmid JA, Wajant H: Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8. J Cell Sci 2002, 115:2757–2770.PubMed
20.
Kim JE, Ryu HJ, Yeo SI, Kang TC: P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus. J Neuroinflammation 2010, 7:65.CrossRefPubMedPubMedCentral
21.
Hayashi M, Luo Y, Laning J, Strieter RM, Dorf ME: Production and function of monocyte chemoattractant protein-1 and other beta-chemokines in murine glial cells. J Neuroimmunol 1995, 60:143–150.CrossRefPubMed
22.
Otto VI, Heinzel-Pleines UE, Gloor SM, Trentz O, Kossmann T, Morganti-Kossmann MC: sICAM-1 and TNF-alpha induce MIP-2 with distinct kinetics in astrocytes and brain microvascular endothelial cells. J Neurosci Res 2000, 60:733–742.CrossRefPubMed
23.
Rhodes JK, Sharkey J, Andrews PJ: The temporal expression, cellular localization, and inhibition of the chemokines MIP-2 and MCP-1 after traumatic brain injury in the rat. J Neurotrauma 2009, 26:507–525.CrossRefPubMed
24.
Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates. 3rd edition. San Diego, Academic Press; 1997.
25.
Kang TC, Kim DS, Kwak SE, Kim JE, Won MH, Kim DW, Choi SY, Kwon OS: Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy. Glia 2006, 54:258–271.CrossRefPubMed
26.
Biagas KV, Uhl MW, Schiding JK, Nemoto EM, Kochanek PM: Assessment of posttraumatic polymorphonuclear leukocyte accumulation in rat brain using tissue myeloperoxidase assay and vinblastine treatment. J Neurotrauma 1992, 9:363–371.CrossRefPubMed
27.
Babcock AA, Kuziel WA, Rivest S, Owens T: Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci 2003, 23:7922–7930.PubMed
28.
Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A: Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 2004, 24:7829–7836.CrossRefPubMed
29.
Farkas G, Márton J, Nagy Z, Mándi Y, Takács T, Deli MA, Abrahám CS: Experimental acute pancreatitis results in increased blood-brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6. Neurosci Lett 1998, 242:147–150.CrossRefPubMed
30.
Viatour P, Merville MP, Bours V, Chariot A: Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci 2005, 30:43–52.CrossRefPubMed
31.
32.
Sternberger NH, Sternberger LA, Kies MW, Shear CR: Cell surface endothelial proteins altered in experimental allergic encephalomyelitis. J Neuroimmunol 1989, 21:241–248.CrossRefPubMed
33.
Perdiki M, Farooque M, Holtz A, Li GL, Olsson Y: Expression of endothelial barrier antigen immunoreactivity in blood vessels following compression trauma to rat spinal cord. Temporal evolution and relation to the degree of the impact. Acta Neuropathol 1998, 96:8–12.CrossRefPubMed
34.
Krum JM, Kenyon KL, Rosenstein JM: Expression of blood-brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin. Exp Neurol 1997, 146:33–45.CrossRefPubMed
35.
Ghabriel MN, Zhu C, Leigh C: Electron microscope study of blood-brain barrier opening induced by immunological targeting of the endothelial barrier antigen. Brain Res 2002, 934:140–151.CrossRefPubMed
36.
Lawrenson JG, Ghabriel MN, Reid AR, Gajree TN, Allt G: Differential expression of an endothelial barrier antigen between the CNS and the PNS. J Anat 1995, 186:217–221.PubMedPubMedCentral
37.
Rosenstein JM, Krum JM, Sternberger LA, Pulley MT, Sternberger NH: Immunocytochemical expression of the endothelial barrier antigen (EBA) during brain angiogenesis. Dev Brain Res 1992, 66:47–54.CrossRef
38.
Sternberger NH, Sternberger LA, Kies MW, Shear CR: Cell surface endothelial proteins altered in experimental allergic encephalomyelitis. J Neuroimmunol 1989, 21:241–248.CrossRefPubMed
39.
40.
Tinsley JM, Blake DJ, Zuellig RA, Davies KE: Increasing complexity of the dystrophin-associated protein complex. Proc Natl Acad Sci USA 1994, 91:8307–8313.CrossRefPubMedPubMedCentral
41.
Bird TA, Schooley K, Dower SK, Hagen H, Virca GD: Activation of nuclear transcription factor NF-kappaB by interleukin-1 is accompanied by casein kinase II-mediated phosphorylation of the p65 subunit. J Biol Chem 1997, 272:32606–32612.CrossRefPubMed
42.
De Simoni MG, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F, De Luigi A, Garattini S, Vezzani A: Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci 2000, 12:2623–2633.CrossRefPubMed
43.
Fuentes ME, Durham SK, Swerdel MR, Lewin AC, Barton DS, Megill JR, Bravo R, Lira SA: Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1. J Immunol 1995, 155:5769–5776.PubMed
Metadata
Title
Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus
Authors
Ji-Eun Kim
Hea Jin Ryu
Soo Young Choi
Tae-Cheon Kang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-6

Other articles of this Issue 1/2012

Journal of Neuroinflammation 1/2012 Go to the issue

Research

Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury

Research

NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9

Research

Variability in detection and quantification of interferon β-1b–induced neutralizing antibodies

Research

Decreased MHC I expression in IFN gamma mutant mice alters synaptic elimination in the spinal cord after peripheral injury

Research

Opposing effects of Toll-like receptors 2 and 4 on synaptic stability in the spinal cord after peripheral nerve injury

Short report

Preserved vascular integrity and enhanced survival following neuropilin-1 inhibition in a mouse model of CD8 T cell-initiated CNS vascular permeability