A study published in the journal Brainindicates that the innate immune response to toll-like receptor 4 (TLR4) ligands, most likely involving activated microglia and release of interleukin (IL)-1, results in increased neuronal excitability sufficient to trigger experimental seizures in vivo.
An increasing body of evidence suggests that inflammatory processes may play an important role in the initiation of seizures and epileptogenesis. This includes both the generation of individual seizures and the process by which a previously normal brain might become epileptic (epileptogenesis).
Glial cells have long been thought to provide only metabolic/structural support in the cerebral cortex. Microglia are activated by central infection, trauma and ischemia. Of note, glial cells are clearly activated following seizures in experimental models of epileptic foci, and this is associated with increased local IL-1β mRNA expression.
In the Brain journal’s study Krista Rodgers and co-workers from the Department of Psychology and Neuroscience, University of Colorado, USA demonstrate that the cortical innate immune responses contribute to enhanced brain excitability resulting in focal seizures.
The authors found that the cortical application of bacterial lipopolysaccharide (LPS), binding to TLR4, produced spontaneous epileptiform discharges. Application of IL-1ra prior to LPS prevented both seizures and epileptiform spikes in tested animals, indicating the involvement of IL-1.
Rodgers et al. discuss that IL-1 may increase neuronal excitability through its activating effect on astrocytes, interfering with their control of glutamate homeostasis. IL-1 released by microglia and/or astrocytes may also have direct effects on neuronal channels and excitability.
This study suggests an important role of innate immune responses and pro-inflammatory cytokines in epileptogenesis. The findings could help prevent acquired epilepsy, which is often found in people who have suffered a brain injury or infection.