Astrocytes and Epilepsy

Abstract

Summary: Astrocytes form a significant constituent of seizure foci in the human brain. For a long time it was believed that astrocytes play a significant role in the causation of seizures. With the increase in our understanding of the unique biology of these cells, their precise role in seizure foci is receiving renewed attention. This article reviews the information now available on the role of astrocytes in the hippocampal seizure focus in patients with temporal lobe epilepsy with hippocampal sclerosis. Our intent is to try to integrate the available data. Astrocytes at seizure foci seem to not be a homogeneous population of cells, and in addition to typical glial fibrillary acidic protein, positive reactive astrocytes also include a population of neuron glia-2-like cells The astrocytes in sclerotic hippocampi differ from those in nonsclerotic hippocampi in their membrane physiology, having elevated Naϩ channels and reduced inwardly rectifying potassium ion channels, and some having the capacity to generate action potentials. They also have reduced glutamine synthetase and increased glutamate dehydrogenase activity. The molecular interface between the astrocyte and microvasculature is also changed. The astrocytes are also associated with increased expression of many molecules normally concerned with immune and inflammatory functions. A speculative mechanism postulates that neuron glia-2-like cells may be involved in creating a high glutamate environment, whereas the function of more typical reactive astrocytes contribute to maintain high extracellular Kϩ levels; both factors contributing to the hyperexcitability of subicular neurons to generate epileptiform activity. The functions of the astrocyte vascular interface may be more critical to the processes involved in epileptogenesis.

The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus

“…We demonstrated that a PPARc agonist can modulate the GSH system balance, and inhibit astrocyte activation, which may relate to an antioxidative mechanism as astrocytes support neurons with precursors for GSH synthesis [33] and release of GSH from astrocytes is neuroprotective. However, under epileptic conditions, astrocytes are not neurosupportive, but rather release proinflammatory cytokines and free radicals which accelerate neuronal loss [34]. Therefore, our data suggest that increased release of GSH by rosiglitazone plays a key role in attenuating oxidative damage in epileptic rats, potentially through its inhibitory actions on astrocyte activation.…”

Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats

“…In epilepsy, astrocytes have been reported to transform into ''reactive astrocytes'' (Belluardo et al, 1996;Hansen et al, 1990;Pollen and Trachtenberg, 1970), which are morphologically characterized by increased volume in humans (Binder and Steinhauser, 2006;de Lanerolle et al, 2010;Kim et al, 2009Kim et al, , 2010 and by disorganized architecture of process tufts and domain overlapping in mice (Oberheim et al, 2008).…”

Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes

“…Reactive astrogliosis occurs in response to all forms of CNS insults including trauma, infections, stroke, neurodegeneration, and epilepsy (1)(2)(3). In most cases, astrocytes become transiently hypertrophic and express high levels of intermediate filament proteins such as glial fibrillary acid protein (GFAP) 3 and vimentin (4,5).…”