Immune Profile in Blood Following Non-convulsive Epileptic Seizures in Rats

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.

Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy

“…KC/GRO levels were, however, not significantly increased during control conditions, suggesting that the blocking of the release of KC/GRO via P2X7R is restricted to pathological conditions (i.e., status epilepticus, epilepsy) when high amounts of extracellular ATP are available to activate the P2X7R [ 61 ]. In contrast to our studies which showed no differences in KC/GRO levels between control conditions and status epilepticus/epilepsy in plasma, previous data have shown increased KC/GRO protein levels in the hippocampus of rats 12 h post-status epilepticus [ 62 ], in the brain and in plasma of rats with non-convulsive status epilepticus [ 63 ], and in the CSF of pediatric patients with febrile infection-related epilepsy syndrome [ 64 ]. Differences in models used, timing of sampling post-status epilepticus, or tissue may account for these observed differences between studies, which should be addressed in the future.…”

Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders

“…The signs of neuroinflamma tion following LPS administration were also maintained for a long time. Analysis of the microglia response to the intra hippocampal infusion of LPS (10 μg) showed an increased number of activated microglial cells at all times (6 and 24 h, 1 and 4 weeks) after endotoxin administra tion [76].…”

Emerging Roles of T Helper Cells in Non-Infectious Neuroinflammation: Savior or Sinner

“…Silverberg et al utilized extracranially placed electrodes to potentiate seizures in mice, and they observed peripheral lymphocytes (including Th cells) infiltration into the brain 24 h after a maximal seizure, which peaked at 48 h and became undetectable at 7 d ( 234). Avdic et al utilized intracranial electrode to induce non-convulsive status epileptics, a prolonged epileptic seizure with subtle symptoms, in rats (265). They reported increased levels of IL-6 in both brain and serum 6 h after non-convulsive epileptic seizures, and after 4 weeks when 75% of those rats exhibited spontaneous seizures (SS), they further compared those rats with SS to both those without and unstimulated rats, finding a decrease of CD4 + T cells in the peripheral blood.…”