RESUMEN
Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.
RESUMEN
BACKGROUND: Adequate function of the nervous system depends on the balance of glianeuron complex interactions. Astrocytes, in particular, are key elements in this process due to the significant participation of these cells in essential properties of the nervous system such as neuroinflammation, regulation of neurotransmitters, release of gliotransmitters and control of synaptic plasticity, among others. Astrocytes express the receptor for advanced glycation end products (RAGE) which is very important in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. RAGE can bind several advanced glycation end products, S100 proteins, HMGB1, amyloid-ß and other additional DAMP molecules. The nuclear factorkappa B (NF-κB) transcription pathway is the main intracellular signaling pathway activated by the RAGE receptor, inducing an increase in the expression and release of proinflammatory cytokines. Due to its numerous interactions, RAGE is suspected to be involved in various physiological and pathological processes. CONCLUSION: It is plausible that a prolonged exposure to RAGE ligands or abnormally increased concentrations of some ligands may induce lengthy periods of intracellular proinflammatory activation, which may induce the appearance of reactive astrocytes involved in the development and/or progression of neurodegenerative disorders. Blocking or reducing the duration of activation of RAGE/NF-κB signaling in astrocytes may become an important therapeutic alternative for the treatment of neurodegenerative disorders in the future.