Behavioral comorbidities of epilepsy and neuroinflammation: Evidence from experimental and clinical studies

Currently, a significant amount of data is accumulated showing that neuroinflammation is one of the key processes in the development of brain pathology in trauma, neurodegenerative diseases, and epilepsy. Various brain insults, such as prolonged seizure activity, trigger the activation of microglia and astrocytes in the brain. These cells, in turn, begin to synthesize pro-inflammatory cytokines. The inflammatory response to the insult causes a cascade of processes leading to a wide range of pathological effects, including changes in neuronal excitability, long-term plastic changes, astrocyte dysfunction, impaired blood-brain barrier (BBB) permeability, and neurodegeneration. These effects may ultimately contribute to the development of chronic spontaneous seizures. On the other hand, neuroinflammation contributes to the pathogenesis of a number of neuropsychiatric disorders. Therefore, neuroinflammation can be a link between epilepsy and its comorbidities, such as mood and anxiety disorders and memory impairment. The mechanisms behind these behavioral and cognitive impairments remain not fully understood. In this paper, clinical evidence of an important role of neuroinflammation in epilepsy and potentially comorbid neurological disorders is reviewed, as well as possible mechanisms of its involvement in the pathogenesis of these conditions obtained from experimental data.