Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 36

Available studies suggest that seizure-related or injury-related inflammation might contribute to cell loss and synaptic reorganization, which are important mediators of the development of hyperexcitable circuits that lead to epilepsy after insults such as status epilepticus or TBI in the adult rodent brain (Bartfai and Schultzberg, 1993; Buckmaster and Dudek, 1997; Pitkanen and Sutula, 2002). Inflammation is induced rapidly following such insults, preceding neurodegeneration in lesional models of seizures (Rizzi et al., 2003; Ravizza and Vezzani, 2006). This finding is consistent with the idea that inflammation augments cell death, which is further supported by data from studies involving injection of inflammatory mediators together with excitotoxic stimuli (Allan et al., 2005). Activation of microglia and astrocytes and production of cytokines and PGE2 can occur in seizure models where cell loss is not detected in immature or adult rodents (Vezzani et al., 1999, 2000a; Rizzi et al., 2003; Kovacs et al., 2006; Dube et al., 2010). Such observations suggest that rather than being a consequence of cell loss, seizure-induced brain inflammation can contribute to cell death (Vezzani and Baram, 2007). Additional interactions between inflammation and cell death in the context of epilepsy have been observed. Brain injury, such as TBI, causes tissue inflammation that seems to contribute to both cell death and long-term hyperexcitability (Clausen et al., 2009; Longhi et al., 2009). In the context of CNS injury (for example, in chronic neurodegenerative diseases or acute stroke), inflammation can have a neuroprotective role (Liesz et al., 2009; Schwartz and Shechter, 2010). Indeed, whether micro-glia, macrophages and/or T cells are destructive or neuroprotective seems to depend on their activation status, which is orchestrated by the specific inflammatory environment (Rothwell, 1989; Schwartz and Shechter, 2010). This balance, together with the specific brain regions in which inflammation develops, might account for the relatively low incidence of seizures in other neurological disorders associated with brain inflammation (Vezzani et al., 2013).