The Role of Astrocyte Dysfunction in the Pathogenesis of Epilepsy

Kieran Boochoon

Introduction: Astrocytes are a subtype of glial cell that have important functions maintaining ion concentrations, water transport, and neurotransmitter levels during neuronal activity.1 Recent studies have implicated that astrocytes could an important role in the pathogenesis of epilepsy. Different processes such as astrocytic Kir channels2, aquaporin channels3, gap junctions4, glutamate transporters5,6, and glutamine synthase7 have demonstrated potential links between astrocyte dysfunction and the development of epilepsy in animal models. Current treatments for epilepsy are only beneficial in suppressing symptoms8 and the effectiveness of the antiepileptic drugs have not improved drastically over the past decade.9 Studies are now focusing on patient models to figure out the correlation between astrocyte dysfunction and the onset of epilepsy. Methods: Based on an experiment from Das et. al. the tissue hippocampal samples were obtained with patient consent from six patients with pharmacoresistant temporal lobe epilepsy and three sudden death patient control samples. Hippocampal slices were surgically removed from patients by the same neurosurgeon with the equivalent surgical technique. The clinicopathological characteristics of the astrocytes were identified using a hematoxylin and eosin stain. Also, immunohistological staining and Western blotting were used to analyze the samples for AQP4 channels, Kir Channels, connexon 43 gap junctions, dystrophin, and alpha-syntrophin .10 Results: The immunofluorescence stain identified an increase and more widespread AQP4 channels in epileptic tissue compared to the sudden death control. In addition, there was approximately a 50% decrease in the amount of Kir channels in the patients with temporal lobe epilepsy leading to the idea that dysregulation of potassium channels is an important part in the pathogenesis of epilepsy. Furthermore, the Western blot analysis demonstrated a reduced amount of alpha-syntrophin and dystrophin, however the Cx43 levels increased 1.5 fold in the epileptic samples.10 Conclusion: This study has demonstrated that there are multiple changes in astrocytic function from patients with refractory temporal lobe epilepsy. Current studies have not elucidated if these changes are involved the pathogenesis of epilepsy or are an effect of epilepsy. Future studies that use in vivo models and modern molecular processes may give researchers the opportunity to clarify the specific roles of astrocytes in epilepsy. In conclusion, research of astrocytes in epilepsy is still in its infancy, however increasing evidence suggests a critical role of astrocytes in homeostasis and seizure generation. The role of astrocytes in epilepsy suggests a new avenue of treatment that can potentially revolutionize the effectiveness of current antiepileptic therapies.

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