Inflammation and endothelium response in epileptic patients: A case-control study

Authors

1 Department of Physiology, Applied Physiology Research Center; Medical Student Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Physiology, Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Isfahan Neurosciences Research Center, Isfahan Medical Education Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Blood brain barrier (BBB) permeability plays an important role in the brain impairments. The barrier is composed of endothelium cells, due to the presence of tight junctions that connect endothelium cells. The failure of BBB function has triggering chronic or acute seizures through brain inflammation and BBB permeability. Seizure induces vasodilation, BBB leakage and up-regulation of vascular cell adhesion molecules which able to bind integrins blood leukocytes.
Materials and Methods: In this case-control study we included 40 epileptic patients who were sampled during a seizure as a case group and 20 healthy subjects as a healthy control group. Plasma levels of the inflammation and endothelium markers including intercellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), interleukin 1 beta (IL-1β) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assays (ELISAs).
Results: The ICAM and VCAM concentration in the epileptic patients (135.8 ± 5.35) (52.04 ± 4.24) were significantly higher than healthy control group (110.32 ± 5.04) (23.38 ± 3.01) (P < 0.005). IL-1 beta concentration was not significantly different between groups (P = 0.594). However, CRP level was significantly up-regulated in epileptic patients (P < 0.005).
Conclusion: Epileptic patients have BBB leakage and dysfunction as the up-regulation of the endothelium cytokines showed. The BBB leakage may be the result of the inflammatory impairment

Keywords

1.
Ivens S, Gabriel S, Greenberg G, Friedman A, Shelef I. Blood-brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome. J Neurol 2010;257:615-20.  Back to cited text no. 1
    
2.
Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia 2006;47:1761-74.  Back to cited text no. 2
    
3.
Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med 2011;17:439-47.  Back to cited text no. 3
    
4.
Winkler MK, Chassidim Y, Lublinsky S, Revankar GS, Major S, Kang EJ, et al. Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: Possible link to blood-brain barrier dysfunction. Epilepsia 2012;53 Suppl 6:22-30.  Back to cited text no. 4
    
5.
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol 2011;7:31-40.  Back to cited text no. 5
    
6.
Vezzani A, Aronica E, Mazarati A, Pittman QJ. Epilepsy and brain inflammation. Exp Neurol 2011;232:143-8.  Back to cited text no. 6
    
7.
Kim SY, Buckwalter M, Soreq H, Vezzani A, Kaufer D. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis. Epilepsia 2012;53 Suppl 6:37-44.  Back to cited text no. 7
    
8.
Fabene PF, Navarro Mora G, Martinello M, Rossi B, Merigo F, Ottoboni L, et al. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med 2008;14:1377-83.  Back to cited text no. 8
    
9.
Zattoni M, Mura ML, Deprez F, Schwendener RA, Engelhardt B, Frei K, et al. Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. J Neurosci 2011;31:4037-50.  Back to cited text no. 9
    
10.
Marchi N, Oby E, Batra A, Uva L, De Curtis M, Hernandez N, et alIn vivo and in vitro effects of pilocarpine: Relevance to ictogenesis. Epilepsia 2007;48:1934-46.  Back to cited text no. 10
    
11.
Marchi N, Johnson AJ, Puvenna V, Johnson HL, Tierney W, Ghosh C, et al. Modulation of peripheral cytotoxic cells and ictogenesis in a model of seizures. Epilepsia 2011;52:1627-34.  Back to cited text no. 11
    
12.
Holtman L, van Vliet EA, Aronica E, Wouters D, Wadman WJ, Gorter JA. Blood plasma inflammation markers during epileptogenesis in post-status epilepticus rat model for temporal lobe epilepsy. Epilepsia 2013;54:589-95.  Back to cited text no. 12
    
13.
Lehtimäki KA, Keränen T, Palmio J, Mäkinen R, Hurme M, Honkaniemi J, et al. Increased plasma levels of cytokines after seizures in localization-related epilepsy. Acta Neurol Scand 2007;116:226-30.  Back to cited text no. 13
    
14.
Alapirtti T, Rinta S, Hulkkonen J, Mäkinen R, Keränen T, Peltola J. Interleukin-6, interleukin-1 receptor antagonist and interleukin-1beta production in patients with focal epilepsy: A video-EEG study. J Neurol Sci 2009;280:94-7.  Back to cited text no. 14
    
15.
Tuttolomondo A, Di Sciacca R, Di Raimondo D, Renda C, Pinto A, Licata G. Inflammation as a therapeutic target in acute ischemic stroke treatment. Curr Top Med Chem 2009;9:1240-60.  Back to cited text no. 15
    
16.
Librizzi L, Regondi MC, Pastori C, Frigerio S, Frassoni C, de Curtis M. Expression of adhesion factors induced by epileptiform activity in the endothelium of the isolated guinea pig brain in vitro. Epilepsia 2007;48:743-51.  Back to cited text no. 16
    
17.
Eid T, Brines ML, Cerami A, Spencer DD, Kim JH, Schweitzer JS, et al. Increased expression of erythropoietin receptor on blood vessels in the human epileptogenic hippocampus with sclerosis. J Neuropathol Exp Neurol 2004;63:73-83.  Back to cited text no. 17
    
18.
Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 2004;24:7829-36.  Back to cited text no. 18
    
19.
Uva L, Librizzi L, Marchi N, Noe F, Bongiovanni R, Vezzani A, et al. Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated Guinea-pig brain requires enhancement of blood-brain barrier permeability. Neuroscience 2008;151:303-12.  Back to cited text no. 19
    
20.
van Vliet EA, Aronica E, Gorter JA. Blood-brain barrier dysfunction, seizures and epilepsy. Semin Cell Dev Biol 2015;38:26-34.  Back to cited text no. 20
    
21.
Tomkins O, Feintuch A, Benifla M, Cohen A, Friedman A, Shelef I. Blood-brain barrier breakdown following traumatic brain injury: A possible role in posttraumatic epilepsy. Cardiovasc Psychiatry Neurol 2011;2011:765923.  Back to cited text no. 21
    
22.
Mantovani A, Garlanda C, Doni A, Bottazzi B. Pentraxins in innate immunity: From C-reactive protein to the long pentraxin PTX3. J Clin Immunol 2008;28:1-13.  Back to cited text no. 22
    
23.
Alapirtti T, Waris M, Fallah M, Soilu-Hänninen M, Mäkinen R, Kharazmi E, et al. C-reactive protein and seizures in focal epilepsy: A video-electroencephalographic study. Epilepsia 2012;53:790-6.  Back to cited text no. 23
    
24.
Tan TY, Lu CH, Chuang HY, Lin TK, Liou CW, Chang WN, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia 2009;50:1579-86.  Back to cited text no. 24