Abstract
Astrocytes are key homeostatic regulators in the central nervous system and play important roles in physiology. After brain damage caused by e.g., status epilepticus, traumatic brain injury, or stroke, astrocytes may adopt a reactive phenotype. This process of reactive astrogliosis is important to restore brain homeostasis. However, persistent reactive astrogliosis can be detrimental for the brain and contributes to the development of epilepsy. In this review, we will focus on physiological functions of astrocytes in the normal brain as well as pathophysiological functions in the epileptogenic brain, with a focus on acquired epilepsy. We will discuss the role of astrocyte-related processes in epileptogenesis, including reactive astrogliosis, disturbances in energy supply and metabolism, gliotransmission, and extracellular ion concentrations, as well as blood-brain barrier dysfunction and dysregulation of blood flow. Since dysfunction of astrocytes can contribute to epilepsy, we will also discuss their role as potential targets for new therapeutic strategies.
Highlights
Epilepsy is a common neurological disease that is estimated to affect roughly 1–2% of the population [1]
It is hypothesized that worsening of seizure activity in mice deficient of astrocytic panx-1 is likely connected to increased adenosine kinase (ADK) levels in astrocytes
The most critical ion flux governed by astrocytes in relation to epilepsy is that of potassium
Summary
Epilepsy is a common neurological disease that is estimated to affect roughly 1–2% of the population [1]. Despite the fact that quite some anti-epileptic drugs (AEDs) have been developed in the last decades, a large number of patients still fail to respond to these AEDs. Despite the fact that quite some anti-epileptic drugs (AEDs) have been developed in the last decades, a large number of patients still fail to respond to these AEDs This is associated with increased morbidity and mortality and since these patients need life-long care this is an economic burden for society. Astrocytes should be considered as promising targets for new therapeutic strategies. The human brain is comprised of ∼100 billion cells, classically divided into neurons and glial cells, new types of brain cells are still being discovered up to date [3, 4]. Glia cells in the central nervous system are typically classified into four cell types: [1] astrocytes, [2] microglia, [3] oligodendrocytes, and [4] their progenitors, neuron-glial antigen 2(NG2)-glia [5]. It has been shown that the actual ratio of glial cells compared to neurons is closer to 1:1 and may be lower than
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