Role of Brain Inflammation in Epileptogenesis

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.

Hydroalcoholic extract ofEmblica officinalisprotects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory, and neuroprotective intervention

“…However, the role of inflammatory responses in the pathogenesis of epilepsy and seizure-induced brain damage has been appreciated only recently. Inflammatory processes, including activation of microglia and astrocytes and production of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and related molecules, have been described in human epilepsy patients as well as in experimental models of epilepsy (Vezzani & Granata, 2005;Choi & Koh, 2008). TNF-α, IL-1β, and IL-1ra are highly inducible under different forms of stress, such as excitatory neurotransmitter excess occurring during seizures, in infection and inflammation, and during neurotrauma (Bartfai et al, 2007).…”

NNZ-2566, a Glypromate Analog, Attenuates Brain Ischemia-Induced Non-Convulsive Seizures in Rats

“…There is also compelling evidence that inflammatory cytokines or immune reactions after brain injury have an important role in neuronal excitability and epileptogenesis (Choi and Koh, 2008;Fabene et al, 2008;Vezzani et al, 2008a). Studies have shown that soon after an acute brain injury, activated microglia and astrocytes provide a rich source of cytokines such as interleukin (IL)-6, IL-1b, and tumor necrosis factor a (Choi and Koh, 2008;Ridet et al, 1997;Rizzi et al, 2003;Viviani et al, 2003), which promote neuronal excitability by modulating extracellular glutamate levels Vezzani et al, 2008b). IL-1b was reported to be responsible for increasing N-methyl-D-aspartate receptor-mediated Ca 2 + influx and surface expression of AMPA receptor by binding to the AMPA receptor IL-1RI, which colocalizes with N-methyl-D-aspartate receptors (Viviani et al, 2003).…”

Modulation of Immunity and the Inflammatory Response: A New Target for Treating Drug-resistant Epilepsy

“…Recently, growing evidence has demonstrated that immune system dysfunction and inflammatory signaling may play an instrumental role in all the phases of the epilepsy development [14-16]. Modulation of immunity and inflammatory response exerted remarkable protective effects on the epilepsy brain in experimental animal studies [17, 18]. Meanwhile, auto-antibodies were detected in the DRE patients and immunotherapy has been shown to benefit these patients [19].…”