Abstract
Non-convulsive status epilepticus (NCSE) is a prolonged epileptic seizure with subtle symptoms that may delay clinical diagnosis. Emerging experimental evidence shows brain pathology and epilepsy development following NCSE. New diagnostic/prognostic tools are therefore needed for earlier and better stratification of treatment. Here we examined whether NCSE initiates a peripheral immune response in blood serum from rats that experienced electrically-induced NCSE. ELISA analysis showed an acute transient increase in serum protein levels including interleukin-6 6 h post-NCSE, similar to the immune reaction in the brain. At 4 weeks post-NCSE, when 75% of rats subjected to NCSE had also developed spontaneous seizures, several immune proteins were altered. In particular, markers associated with microglia, macrophages and antigen presenting cells, such as CD68, MHCII, and galectin-3, were increased and the T-cell marker CD4 was decreased in serum compared to both non-stimulated controls and NCSE rats without spontaneous seizures, without correlation to interictal epileptiform activity. Analyses of serum following intracerebral injection of lipopolysaccharide (LPS) showed an acute increase in interleukin-6, but at 4 weeks unaltered levels of MHCII and galectin-3, an increase in CD8 and CD11b and a decrease in CD68. None of the increased serum protein levels after NCSE or LPS could be confirmed in spleen tissue. Our data identifies the possibility to detect peripheral changes in serum protein levels following NCSE, which may be related to the development of subsequent spontaneous seizures.
Highlights
Status epilepticus (SE) is a prolonged epileptic seizure with continuous epileptiform brain activity that if not interrupted can develop into a serious medical condition
Continuous video-EEG recordings after non-convulsive SE (NCSE) showed that 75% of the rats that were subjected to NCSE in the 4 w survival group exhibited spontaneous seizures during week 2–4 and 25% only displayed acute symptomatic seizures within the first week
The immune response within the epileptic focus in the brain included an acute release of IL-6, keratinocyte chemoattractant/growth related oncogene (KC/GRO), and tumor necrosis factor (TNF)-α following NCSE and was associated with a simultaneous increase in IL-6 and KC/GRO in serum but not in spleen tissue
Summary
Status epilepticus (SE) is a prolonged epileptic seizure with continuous epileptiform brain activity that if not interrupted can develop into a serious medical condition. An innate immune reaction in the brain as a result of NCSE leads to activation and recruitment of systemic immune cells, as observed experimentally in a kainic acid model of temporal lobe epilepsy [9]. Acute infiltration of CD4+ and CD8+ T cells into the brain at 24–72 h following a single tonic-clonic seizure has been reported [10, 11], along with long-lasting monocyte and lymphocyte infiltration in both clinical and experimental studies of epilepsy [12]. Altered levels of CD8 have been observed in experimental models of SE [13, 14] and infiltrating CD45+ leukocytes and CD3+ lymphocytes have been observed within resected temporal lobes from patients with severe therapy-resistant temporal lobe epilepsy [9]
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