Yonsei Med J.  2008 Feb;49(1):1-18.

Role of Brain Inflammation in Epileptogenesis

• Choi J
• Koh S

Abstract

Inflammation is known to participate in the mediation of a growing number of acute and chronic neurological disorders. Even so, the involvement of inflammation in the pathogenesis of epilepsy and seizure-induced brain damage has only recently been appreciated. Inflammatory processes, including activation of microglia and astrocytes and production of proinflammatory cytokines and related molecules, have been described in human epilepsy patients as well as in experimental models of epilepsy. For many decades, a functional role for brain inflammation has been implied by the effective use of anti-inflammatory treatments, such as steroids, in treating intractable pediatric epilepsy of diverse causes. Conversely, common pediatric infectious or autoimmune diseases are often accompanied by seizures during the course of illness. In addition, genetic susceptibility to inflammation correlated with an increased risk of epilepsy. Mounting evidence thus supports the hypothesis that inflammation may contribute to epileptogenesis and cause neuronal injury in epilepsy. We provide an overview of the current knowledge that implicates brain inflammation as a common predisposing factor in epilepsy, particularly childhood epilepsy.

Keyword

Epilepsy; childhood; steroid; cytokine; innate immunity; microglia; astrocytes

MeSH Terms

Animals
Blood-Brain Barrier
Chronic Disease
Encephalitis/genetics/immunology/metabolism/*pathology
Epilepsy/immunology/metabolism/*pathology/therapy
Gene Expression Regulation
Humans
Nervous System Diseases/immunology/pathology

Figure

• 

  Fig. 1 Acute activation of microglia after KA-induced seizures in CX3cr1EGFP/+ transgenic mice. (A) Low magnification view of a brain section from a Cx3cr1GFP/+ transgenic mouse showing that all parenchymal microglia are fluorescently labeled green because the Cx3cr1-encoding fractalkine chemokine receptor has been replaced by a green fluorescent protein (GFP) reporter gene. The box points to massively accumulated microglia one week after KA-induced seizures, likely at the area of injury, shown in high magnification view (B). High magnification view of PBS control (C) and KA-induced seizures (D). Within two days after status epilepticus, a nearly two-fold increase in the area of fluorescent cells and significant microglial proliferation were noted in KA-treated mice compared to control littermates. Note the ramified processes and apparent increase in the number of GFP+ microglia.

• 

  Fig. 2 Time course of changes in expression of select inflammation-related genes significantly regulated in rats after KA at P15 and P30 compared to controls. Genes (C) for transcription factors known to be early mediators of immune and inflammation responses, as well as cytokines associated with microglial activation, are rapidly and dramatically up-regulated after KA-induced seizures at P15 (postnatal day 15; juvenile rats) (A) and P30 (postnatal day 30; adult rats) (B). Note that some of these inflammation-related genes are increased to a greater extent than at P15 and are often persistently elevated beyond 72 hours only in adult rats (P30, B) that show seizure-induced cell death and develop spontaneous recurrent seizures.

• 

  Fig. 3 Triple immunofluorescence confocal images of neurons, microglia, and astrocytes in the epileptogenic cortex of patients with chronic intractable childhood epilepsy. (A) Activated microglia (blue) and astrocytes (red) are found in close contact with each other and with neurons (green). Bar = 100µm. (B) Microglial processes (red) wrap around a neuron (green), engulfing fragmented DNA (blue). Bar = 10µm.

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