Inflammation and epilepsy in the developing brain: clinical and experimental evidence

Abstract

There is an increasing evidence to support a role of inflammatory processes in epilepsy. However, most clinical and experimental studies have been conducted in adult patients or using adult rodents. The pediatric epilepsies constitute a varied group of diseases that are most frequently age specific. In this review, we will focus on the possible role of inflammation in pediatric epilepsy syndromes. We will first describe the clinical data available and provide an overview of our current understanding of the role of inflammation in these clinical situations. We will then review experimental data regarding the role of inflammation in epilepsy in the developing brain. To summarize, inflammation contributes to seizure precipitation, and reciprocally, prolonged seizures induce inflammation. There is also a relationship between inflammation and cell injury following status epilepticus, which differs according to the developmental stage. Finally, inflammation seems to contribute to epileptogenesis even in the developing brain. Based on the available data, we highlight the need for further studies dissecting the exact role of inflammation in epilepsy during development.

Keywords: Developing Brain; Epilepsy; Epileptogenesis; IL-1; Inflammation.

Figure 1

Mechanisms of FSs. The association of several factors is involved in each patient, among which are an immature brain, an increase in body temperature, inflammatory responses, genetics, and viral infection. FSs are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Six FS susceptibility loci have been identified: FEB1 (8q13‐q21), FEB2 (19p13.3), FEB4 (5q14‐q15), FEB5 (6q22‐q24), FEB6 (18q11.2), and FEB7 (21q22). Recently, several association studies on FSs have been reported, but the results vary among groups and no consistent or convincing FS susceptibility gene has emerged. IL‐1β increases NMDA receptor function through the activation of tyrosine kinases and subsequent phosphorylation of the NR2A/B (GluN2A/B) subunit, resulting in an increase in NMDA‐induced calcium influx. TNF α causes an increase in the surface expression of neuronal AMPA receptors, responsible for an increase in synaptic efficacy. Viral infections are the most common causes of fever in cases of FSs. Human herpesvirus‐6 and influenza are frequently discussed as possible inducing factors for FSs because of their neurotropic properties, but the role of the viruses and the related inflammatory response remain poorly understood.