The role of inflammation in epilepsy - PubMed (original) (raw)
Review
The role of inflammation in epilepsy
Annamaria Vezzani et al. Nat Rev Neurol. 2011 Jan.
Abstract
Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.
Figures
Figure 1. Pathophysiological cascade of inflammatory events in epilepsy
Pathological events intiated in the CNS by local injuries, or peripherally following infections or as a result of autoimmune disorder, can lead to activation of brain cells or leukocytes, respectively. These cells release inflammatory mediators into the brain or blood, thereby eliciting a cascade of inflammatory events that cause a spectrum of physiopathological outcomes. The effects of brain inflammation contribute to the generation of individual seizures and cell death, which, in turn, activates further inflammation, thereby establishing a vicious circle of events that contributes to the development of epilepsy. The peripheral pathway is shown in yellow, the CNS pathway is shown in blue, and the inflammatory molecules are shown in pink. The merged colors indicate the contribution of each pathway to inflammation and BBB damage. Abbreviations: AP1, activator protein 1; BBB, blood–brain barrier; COX, cyclooxygenase; GABA, γ-aminobutyric acid; HMGB1, high-mobility group box 1; MAPK, mitogen-activated protein kinase; NFκB, nuclear factor kappa B; PI3K, phosphoinositide 3-kinase; PLA2, phospholipases A2; TGF-β, transforming growth factor β; TNF, tumor necrosis factor.
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