Abstract
Mounting evidence supports the involvement of brain inflammation and the associated blood–brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in brain vessels was upregulated 24 h after kainic acid (KA) induced seizures. The aim of the present study was to investigate soluble AM levels in the cerebrospinal fluid (CSF) and serum of epilepsy patients. Paired CSF and serum samples were analyzed by sandwich enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Increased serum concentrations of sICAM-1 were present in epileptic patients (41 localization-related of unknown etiology, 19 idiopathic generalized). Serum sICAM-1 level in drug-refractory epilepsy was elevated as compared to new diagnosis epilepsy and drug-responsive epilepsy. CSF sVCAM-1 and serum sVCAM-1 concentrations in the epilepsy group were higher as compared to the neurosis group. Moreover, CSF sVCAM-1 and serum sVCAM-1 concentrations in drug-refractory epilepsy were raised as compared to drug-responsive epilepsy and new diagnosis epilepsy. However, there were no significant differences in concentrations of CSF sICAM-1 between the epilepsy and neurosis groups. Our results suggest that sVCAM-1 and sICAM-1 could play an important role in the drug-refractory epilepsy.
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References
Aronica E, Crino PB (2011) Inflammation in epilepsy: clinical observations. Epilepsia 52:26–32
Bö L, Peterson JW, Mørk S, Hoffman PA, Gallatin MW, Ransohoff RM, Trapp BD (1996) Distribution of Immunoglobulin superfamily members ICAM-1,-2,-3, and the β2 Integrin LFA-1 in Multiple Sclerosis Lesions. J Neuropathol Exp Neurol 55:1060–1072
Bialer M, White HS (2010) Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68–82
Correale J, Bassani Molinas MM (2003) Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS. J Neuroimmunol 140:198–209
Das A, Wallace Iv G, Holmes C, McDowell M, Smith J, Marshall J, Bonilha L, Edwards J, Glazier S, Ray S (2012) Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors. Neuroscience 220:237–246
Dubé CM, Brewster AL, Richichi C, Zha Q, Baram TZ (2007) Fever, febrile seizures and epilepsy. Trends Neurosci 30:490–496
Fabene PF, Laudanna C, Constantin G (2013) Leukocyte trafficking mechanisms in epilepsy. Mol Immunol 55:100–104
Fabene PF, Mora GN, Martinello M, Rossi B, Merigo F, Ottoboni L, Bach S, Angiari S, Benati D, Chakir A (2008) A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med 14:1377–1383
Khoury S, Orav E, Guttmann C, Kikinis R, Jolesz F, Weiner H (1999) Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis. Neurology 53:758
Kraus J, Oschmann P, Leis S, Neundörfer B, Heckmann J (2002) High concentrations of sVCAM-1 and sICAM-1 in the cerebrospinal fluid of patients with intracerebral haemorrhage are associated with poor outcome. J Neurol Neurosurg Psychiatry 73:346–347
Kwan P, Schachter SC, Brodie MJ (2011) Drug-resistant epilepsy. N Engl J Med 365:919–926
Lee SJ, Benveniste EN (1999) Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol 98:77–88
Librizzi L, Noè F, Vezzani A, de Curtis M, Ravizza T (2012) Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann Neurol 72:82–90
Ma Q, Chen S, Klebe D, Zhang JH, Tang J (2013) Adhesion molecules in CNS Disorders: biomarker and therapeutic targets. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 12:392–404
Oby E, Janigro D (2006) The blood–brain barrier and epilepsy. Epilepsia 47:1761–1774
Rigau V, Morin M, Rousset M-C, de Bock F, Lebrun A, Coubes P, Picot M-C, Baldy-Moulinier M, Bockaert J, Crespel A (2007) Angiogenesis is associated with blood–brain barrier permeability in temporal lobe epilepsy. Brain 130:1942–1956
Seino M (2006) Classification criteria of epileptic seizures and syndromes. Epilepsy Res 70:27–33
Tesa V, Jelinkova E, Jirsa M Jr, Bakosova M, Pitha P, Chabova V (2000) Soluble adhesion molecules and cytokines in patients with myasthenia gravis treated by plasma exchange. Blood Purif 18:115–120
Vezzani A, Aronica E, Mazarati A, Pittman QJ (2013a) Epilepsy and brain inflammation. Exp Neurol 244:11–21
Vezzani A, Friedman A (2011) Brain inflammation as a biomarker in epilepsy. Biomark Med 5:607–614
Vezzani A, Friedman A, Dingledine RJ (2013b) The role of inflammation in epileptogenesis. Neuropharmacology 69:16–24
Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743
Witkowska AM, Borawska MH (2004) Soluble intercellular adhesion molecule-1 (sICAM-1): an overview. Eur Cytokine Netw 15:91–98
Xiao F, Chen D, Lu Y, Xiao Z, Guan L-f, Yuan J, Wang L, Xi Z-q, Wang X-f (2009) Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy. Brain Res 1255:180–189
Zattoni M, Mura ML, Deprez F, Schwendener RA, Engelhardt B, Frei K, Fritschy J-M (2011) Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. J Neurosci 31:4037–4050
Acknowledgments
This work was supported by the funding from National Natural Science Foundation of China (NO. 81100966) and the Chongqing Municipal Education Commission (No. KJ 080307). We are deeply grateful to all of the patients and their families for their participation in this study. We sincerely thank the First Affiliated Hospital of Chongqing Medical University for the support and assistance in CSF and serum procurement. We also great appreciate the Chongqing Key Laboratory of Neurology for technical assistance.
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Jing Luo and Wei Wang contributed equally to this work.
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Luo, J., Wang, W., Xi, Z. et al. Concentration of Soluble Adhesion Molecules in Cerebrospinal Fluid and Serum of Epilepsy Patients. J Mol Neurosci 54, 767–773 (2014). https://doi.org/10.1007/s12031-014-0366-8
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DOI: https://doi.org/10.1007/s12031-014-0366-8