Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease, which is characterized by the degeneration of motor neurons in the motor cortex and the spinal cord and subsequently by muscle atrophy. To date, numerous gene mutations have been linked to both sporadic and familial ALS, but the effort of many experimental groups to develop a suitable therapy has not, as of yet, proven successful. The original focus was on the degenerating motor neurons, when researchers tried to understand the pathological mechanisms that cause their slow death. However, it was soon discovered that ALS is a complicated and diverse pathology, where not only neurons, but also other cell types, play a crucial role via the so-called non-cell autonomous effect, which strongly deteriorates neuronal conditions. Subsequently, variable glia-based in vitro and in vivo models of ALS were established and used for brand-new experimental and clinical approaches. Such a shift towards glia soon bore its fruit in the form of several clinical studies, which more or less successfully tried to ward the unfavourable prognosis of ALS progression off. In this review, we aimed to summarize current knowledge regarding the involvement of each glial cell type in the progression of ALS, currently available treatments, and to provide an overview of diverse clinical trials covering pharmacological approaches, gene, and cell therapies.

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The proper function of the nervous system is dependent on the balance of ions and water between the intracellular and extracellular space (ECS). It has been suggested that the interaction of aquaporin‐4 (AQP4) and the transient receptor potential vaniloid isoform 4 (TRPV4) channels play a role in water balance and cell volume regulation, and indirectly, of the ECS volume. Using the real‐time iontophoretic method, we studied the changes of the ECS diffusion parameters: ECS volume fraction α (α = ECS volume fraction/total tissue volume) and tortuosity λ (λ2 = free/apparent diffusion coefficient) in mice with a genetic deficiency of AQP4 or TRPV4 channels, and in control animals. The used models of cytotoxic edema included: mild and severe hypotonic stress or oxygen‐glucose deprivation (OGD) in situ and terminal ischemia/anoxia in vivo. This study shows that an AQP4 or TRPV4 deficit slows down the ECS volume shrinkage during severe ischemia in vivo. We further demonstrate that a TRPV4 deficit slows down the velocity and attenuates an extent of the ECS volume decrease during OGD treatment in situ. However, in any of the cytotoxic edema models in situ (OGD, mild or severe hypotonic stress), we did not detect any alterations in the cell swelling or volume regulation caused by AQP4 deficiency. Overall, our results indicate that the AQP4 and TRPV4 channels may play a crucial role in severe pathological states associated with their overexpression and enhanced cell swelling. However, detailed interplay between AQP4 and TRPV4 channels requires further studies and additional research.