Wielokomórkowa plastyczność hamowania w epilepsji i śnie: znaczenie dla rozwoju epilepsji pourazowej

Traumatic brain injury (TBI) is a leading cause of acquired epilepsy, and the latent period before the first spontaneous seizure offers a window for anti-epileptogenic intervention. Glial cells are active participants in the pathophysiology of epilepsy and play a role beyond the classical supportive roles and in the control of inhibitory networks. Cumulatively, astrocytes, microglia and oligodendrocytes contribute to the GABAergic signal transduction via orchestrated pathways comprising neurotransmitter uptake, cytokine-mediated inflammation and myelin remodeling. GABA transporters (GAT-1, GAT-3) mediating astrocytes have a major role in modulation of inhibitory tone, connecting circadian genes (such as Bmal1) to sleep-associated alterations in seizure susceptibility. Microglial reactivity and neuroinflammation also disrupt astrocytic inhibitory homeostasis and promote both epileptogenesis and sleep instability. Oligodendrocytes exert activity-dependent myelination on inhibitory networks, affecting seizure propagation and oscillatory synchrony. However, it is unclear how these glial populations interact to control inhibition for NREM sleep, REM sleep, interictal, ictal, and postictal conditions. We present the results of a multi-glial inhibitory plasticity model in this review to extend on the classical tripartite synapse model to integrate astrocytic GABA transport, microglial inflammatory signaling and oligodendrocyte-driven circuit remodeling. This framework suggests that the glial-mediated modulation of inhibitory homeostasis is a state-specific regulatory mechanism in epilepsy and sleep-associated comorbidities, providing a basis for future treatments focusing on stability of the inhibitory network. Because sleep is disrupted early after TBI, the state-dependent glial control of inhibition described here is directly relevant to post-traumatic epileptogenesis.