Abstract
Epilepsy, which affects about 1 % of the population worldwide, leads to poor prognosis and increased morbidity. However, effective drugs providing satisfactory control on seizure relapse were rare, which encouraged more etiological studies. Whether inflammation is one of key events underlying seizure is in debate. In order to explore the role of inflammatory in the pathogenesis and development of epilepsy, we conducted intra-caudal vein injection of leukocytes to aggravated brain inflammatory process in kainic acid-induced seizure model in this study. The results showed that intravenous administration of activated leukocytes increased the frequency and reduced the latent phase of seizure recurrences in rat models of epileptic seizure, during which leukocyte inflammation, brain–blood barrier damage, and neuron injury were also significantly aggravated, indicating that leukocyte infiltration might facilitate seizure recurrence through aggravating brain inflammation, brain–blood barrier damage, and neuron injury.
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Abbreviations
- BBB:
-
Blood–brain barrier
- CD:
-
Cluster of differentiation
- CNS:
-
Central nervous system
- DAB:
-
Diaminobenzidine
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- HRP:
-
Horseradish peroxidase
- ICAM-1:
-
Intercellular cell adhesion molecule-1
- PSGL-1:
-
P-selectin glycoprotein ligand 1
- PVDF:
-
Polyvinylidene fluoride
- SDS-PAGE:
-
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- TLE:
-
Temporal lobe epilepsy
- ZO-1:
-
Zona occludens 1 (tight junction protein 1)
References
Bhalla, D., K. Chea, C. Hun, V. Chan, P. Huc, S. Chan, R. Sebbag, D. Gerard, M. Dumas, S. Oum, M. Druet-Cabanac, and P.M. Preux. 2013. Epilepsy in Cambodia—treatment aspects and policy implications: a population-based representative survey. PLoS One 8, e74817.
Sendrowski, K., and W. Sobaniec. 2013. Hippocampus, hippocampal sclerosis and epilepsy. Pharmacological Reports 65: 555–565.
Tellez-Zenteno, J.F., and L.D. Ladino. 2013. Temporal epilepsy: clinical, diagnostic and therapeutic aspects. Revista de Neurologia 56: 229–242.
Yu, N., H. Liu, and Q. Di. 2013. Modulation of immunity and the inflammatory response: a new target for treating drug-resistant epilepsy. Current Neuropharmacology 11: 114–127.
Janigro, D., P.H. Iffland 2nd, N. Marchi, and T. Granata. 2013. A role for inflammation in status epilepticus is revealed by a review of current therapeutic approaches. Epilepsia Suppl 6: 30–32.
Roberts, J., M.P. Kahle, and G.J. Bix. 2012. Perlecan and the blood-brain barrier: beneficial proteolysis? Frontiers in Pharmacology 3: 155.
Zanini, G.M., P. Cabrales, W. Barkho, J.A. Frangos, and L.J. Carvalho. 2011. Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice. Journal of Neuroinflammation 8: 66.
Lang, K.S., P.A. Lang, A. Meryk, A.A. Pandyra, L.M. Boucher, V.I. Pozdeev, M.W. Tusche, J.R. Gothert, J. Haight, A. Wakeham, A.J. You-Ten, D.R. McIlwain, K. Merches, V. Khairnar, M. Recher, G.P. Nolan, Y. Hitoshi, P. Funkner, A.A. Navarini, A. Verschoor, N. Shaabani, N. Honke, L.Z. Penn, P.S. Ohashi, D. Haussinger, K.H. Lee, and T.W. Mak. 2013. Involvement of Toso in activation of monocytes, macrophages, and granulocytes. Proceedings of the National Academy of Sciences of the United States of America 110: 2593–2598.
Kim, S.Y., M. Buckwalter, H. Soreq, A. Vezzani, and D. Kaufer. 2012. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis. Epilepsia Suppl 6: 37–44.
Vezzani, A., S. Auvin, T. Ravizza, and E. Aronica. 2012. Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators. In Jasper’s basic mechanisms of the epilepsies [Internet], 4th edition, ed. J.L. Noebels, M. Avoli, M.A. Rogawski, R.W. Olsen, and A.V. Delgado-Escueta. Bethesda, MD: National Center for Biotechnology Information (US).
Lyck, R., and B. Engelhardt. 2012. Going against the tide—how encephalitogenic T cells breach the blood-brain barrier. Journal of Vascular Research 49: 497–509.
Wang, H., S. Liu, Z. Tang, and J. Liu. 2014. Some cross-talks between immune cells and epilepsy should not be forgotten. Neurological Sciences 35: 1843–1849.
Engelhardt, B. 2009. PSGL-1—the hidden player in T cell trafficking into the brain in multiple sclerosis? Journal of Leukocyte Biology 86: 1023–1025.
Loacker, S., M. Sayyah, W. Wittmann, H. Herzog, and C. Schwarzer. 2007. Endogenous dynorphin in epileptogenesis and epilepsy: anticonvulsant net effect via kappa opioid receptors. Brain 130(Pt 4): 1017–1028.
Zattoni, M., M.L. Mura, F. Deprez, R.A. Schwendener, B. Engelhardt, K. Frei, and J.M. Fritschy. 2011. Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. The Journal of Neuroscience 31(11): 4037–4050.
Giori, L., S. Gironi, P. Scarpa, A. Anselmi, M. Gualtieri, and S. Paltrinieri. 2011. Grey eosinophils in sighthounds: frequency in 3 breeds and comparison of eosinophil counts determined manually and with 2 hematology analyzers. Veterinary Clinical Pathology 40(4): 475–483.
Fabene, P.F., G. Navarro Mora, M. Martinello, B. Rossi, F. Merigo, L. Ottoboni, S. Bach, S. Angiari, D. Benati, A. Chakir, L. Zanetti, F. Schio, A. Osculati, P. Marzola, E. Nicolato, J.W. Homeister, L. Xia, J.B. Lowe, R.P. McEver, F. Osculati, A. Sbarbati, E.C. Butcher, and G. Constantin. 2008. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nature Medicine 14: 1377–1383.
Fermino, M.L., C.D. Polli, K.A. Toledo, F.T. Liu, D.K. Hsu, M.C. Roque-Barreira, G. Pereira-da-Silva, E.S. Bernardes, and L. Halbwachs-Mecarelli. 2011. LPS-induced galectin-3 oligomerization results in enhancement of neutrophil activation. PLoS One 6(10), e26004.
Harhausen, D., V. Sudmann, U. Khojasteh, J. Muller, M. Zille, K. Graham, A. Thiele, T. Dyrks, U. Dirnagl, and A. Wunder. 2013. Specific imaging of inflammation with the 18 kDa translocator protein ligand DPA-714 in animal models of epilepsy and stroke. PLoS One 8, e69529.
Seiffert, E., J.P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman. 2004. Lasting blood brain barrier disruption induces epileptic focus in the rat somatosensory cortex. The Journal of Neuroscience 24: 7829–7836.
David, Y., L.P. Cacheaux, S. Ivens, E. Lapilover, U. Heinemann, D. Kaufer, and A. Friedman. 2009. Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? The Journal of Neuroscience 29: 10588–10599.
Vezzani, A., J. French, T. Bartfai, and T.Z. Baram. 2011. The role of inflammation in epilepsy. Nature Reviews Neurology 7: 31–40.
Viviani, B., F. Gardoni, and M. Marinovich. 2007. Cytokines and neuronal ion channels in health and disease. International Review of Neurobiology 82: 247–263.
Wetherington, J., G. Serrano, and R. Din-gledine. 2008. Astrocytes in the epileptic brain. Neuron 58: 168–178.
Friedman, A., D. Kaufer, and U. Heinemann. 2009. Blood–brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Research 85: 142–149.
Devinsky, O., A. Vezzani, S. Najjar, N.C. De Lanerolle, and M.A. Rogawski. 2013. Glia and epilepsy: excitability and inflammation. Trends in Neurosciences 36: 174–184.
Tombini, M., R. Squitti, F. Cacciapaglia, M. Ventriglia, G. Assenza, A. Benvenga, G. Pellegrino, C. Campana, F. Assenza, M. Siotto, L. Pacifici, A. Afeltra, and P.M. Rossini. 2013. Inflammation and iron metabolism in adult patients with epilepsy: does a link exist? Epilepsy Research 107: 244–252.
Acknowledgments
This work was supported by a grant from National Natural Science Foundation of China (Contract grant number 81271441). The authors are grateful to Sibo Liu for completing the data collection and analysis.
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Suping Wang and Zanhua Liu contributed equally to this work.
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Liu, Z., Wang, S., Liu, J. et al. Leukocyte Infiltration Triggers Seizure Recurrence in a Rat Model of Temporal Lobe Epilepsy. Inflammation 39, 1090–1098 (2016). https://doi.org/10.1007/s10753-016-0340-4
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DOI: https://doi.org/10.1007/s10753-016-0340-4