Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains

Dupuis, N, Mazarati, A, Desnous, B, Chhor, V, Fleiss, B, Le Charpentier, T, Lebon, S, Csaba, Z, Gressens, P, Dournaud, P and Auvin, S 2016, 'Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains', Journal of Neuroinflammation, vol. 13, no. 1, pp. 1-11.


Document type: Journal Article
Collection: Journal Articles

Title Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains
Author(s) Dupuis, N
Mazarati, A
Desnous, B
Chhor, V
Fleiss, B
Le Charpentier, T
Lebon, S
Csaba, Z
Gressens, P
Dournaud, P
Auvin, S
Year 2016
Journal name Journal of Neuroinflammation
Volume number 13
Issue number 1
Start page 1
End page 11
Total pages 11
Publisher BioMed Central Ltd.
Abstract Background Infectious encephalitides are most often associated with acute seizures during the infection period and are risk factors for the development of epilepsy at later times. Mechanisms of viral encephalitis-induced epileptogenesis are poorly understood. Here, we evaluated the contribution of viral encephalitis-associated inflammation to ictogenesis and epileptogenesis using a rapid kindling protocol in rats. In addition, we examined whether minocycline can improve outcomes of viral-like brain inflammation. Methods To produce viral-like inflammation, polyinosinic-polycytidylic acid (PIC), a toll-like receptor 3 (TLR3) agonist, was applied to microglial/macrophage cell cultures and to the hippocampus of postnatal day 13 (P13) and postnatal day 74 (P74) rats. Cell cultures permit the examination of the inflammation induced by PIC, while the in vivo setting better suits the analysis of cytokine production and the effects of inflammation on epileptogenesis. Minocycline (50 mg/kg) was injected intraperitoneally for 3 consecutive days prior to the kindling procedure to evaluate its effects on inflammation and epileptogenesis. Results PIC injection facilitated kindling epileptogenesis, which was evident as an increase in the number of full limbic seizures at both ages. Furthermore, in P14 rats, we observed a faster seizure onset and prolonged retention of the kindling state. PIC administration also led to an increase in interleukin 1β (IL-1β) levels in the hippocampus in P14 and P75 rats. Treatment with minocycline reversed neither the pro-epileptogenic effects of PIC nor the increase of IL-1β in the hippocampus in both P14 and P75 rats. Conclusions Hippocampal injection of PIC facilitates rapid kindling epileptogenesis at both P14 and P75, suggesting that viralinduced inflammation increases epileptogenesis irrespective of brain maturation. Minocycline, however, was unable to reverse the increase of epileptogenesis, which might be linked to its absence of effect o
Subject Neurology and Neuromuscular Diseases
Keyword(s) Encephalitis
Epileptogenesis
Kindling
Microglia
Minocycline
Toll-like receptor
Virus
DOI - identifier 10.1186/s12974-016-0773-6
Copyright notice © The Author(s). 2016
ISSN 1742-2094
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