Aquaporin water channels in the nervous system

Papadopoulos, Marios C.; Verkman, A. S.

doi:10.1038/nrn3468

Cited by 617 publications

(587 citation statements)

References 158 publications

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“…As AQP4 are simple passive pores, they lack sophisticated gating and transport mechanisms suitable for targeting with small molecules. Furthermore, mutations in the extracellular and cytoplasmic domains of AQP4 generally have little effect on water permeability through the channel, which suggests that the binding of an inhibitor has to occur deep in the narrow pore to physically prevent water conduction (Papadopoulos and Verkman, 2013; Verkman et al, 2014). Nevertheless, further large‐scale screening of random and computationally biased libraries in search of AQP4 blockers is warranted.…”

Section: Potential Therapeutic Targets In Astrocytesmentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem‐cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability. Support of neuroprotective functions of astrocytes is thus an important strategy for enhancing neuronal survival and improving outcomes in disease states. In this review, we first briefly examine how astrocytic dysfunction contributes to major neurological disorders, which are traditionally associated with malfunctioning of processes residing in neurons. Possible molecular entities within astrocytes that could underpin the cause, initiation and/or progression of various disorders are outlined. In the second section, we explore opportunities enhancing neuroprotective function of astroglia. We consider targeting astrocyte‐specific molecular pathways which are involved in neuroprotection or could be expected to have a therapeutic value. Examples of those are oxidative stress defense mechanisms, glutamate uptake, purinergic signaling, water and ion homeostasis, connexin gap junctions, neurotrophic factors and the Nrf2‐ARE pathway. We propose that enhancing the neuroprotective capacity of astrocytes is a viable strategy for improving brain resilience and developing new therapeutic approaches.

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Section: Potential Therapeutic Targets In Astrocytesmentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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“…63 It must be noted that in models of purely vasogenic edema, such as intraparenchymal fluid infusion or freeze-injury where there is a direct insult to the blood brain barrier, AQP4 expression facilitates reabsorption and minimizes injury. 64 So, although there is now a general consensus that following cerebral contusion AQP4 is up regulated, 65,66 studies aimed at understanding the mechanism and potential neuroprotective properties of pharmacological agents must consider that distinct brain injury models trigger vastly different cellular mechanism that may or may not be related to modulation of AQP4.…”

Section: Beneficial Effects Of V1ar Inhibition By Sr49059mentioning

confidence: 99%

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

Filippidis

Liang²,

Wang³

et al. 2014

Journal of Neurotrauma

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Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na. Ion-selective Na + and K + electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na + ] e , [K + ] e , and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na + ] e to 80.1 -15 and 87.9 -7.9 mM and increase in [K + ] e to 20.9 -3.8 and 13.4 -3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p < 0.001 vs. baseline; ns between groups). Importantly, [Na + ] e in CCI-SR49059-ISE was reduced 5-20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na + ] e recovery. In contrast, [K + ] e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na + ] e recovery and reduced ICP. By augmenting the [Na + ] e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI.

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“…In the spinal cord, AQP4 is localized in perivascular astrocyte foot processes and in the glial limiting membrane [1]. Studies have also shown that myelin oligodendrocyte glycoprotein (MOG) may also be a pathogenic antigen in AQP4-Ab negative patients [1,2]. One of the hallmark clinical syndromes suggestive of this disease is LETM, defined as a complete paralysis and sensory loss below the level of the lesion and loss of sphincter control.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Clinical Presentation and MRI Findings in Neuromyelitis optica Spectrum Disorder and Spinal Cord Infarct in Complex Patients with Multiple Co-Morbidities

Guerrero¹

2017

JNSK

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Neuromyelitis optica spectrum disorder (NMOSD) can be difficult to differentiate from other causes of longitudinally extensive transverse my elites (LETM), such as spinal cord infarct (SCI), especially when patients are complex and have multiple co-morbidities. It is therefore of utility to compare the MRI findings in such cases in order to further distil the key characteristics associated with each condition and improve diagnostic accuracy while predicting variability. This case comparison examines two patients with acute LETM that were followed by a single provider. Each patient's clinical history, cervical and thoracic MRI, CSF studies, AQP4-Ab serology and co morbidities are compared, ultimately leading to the final diagnosis of NMOSD and SCI in each patient respectively. In these patients, clinical history differed in time to nadir and precipitating factor of hypotension. Etiology specific features on MRI were found to be unreliable but associated features helped to synthesize the clinical picture. These difficult cases underscore the need for neurologists to be familiar with the differential diagnosis of LETM and to use key distinguishing findings on MRI to help differentiate NMOSD from other diseases such as SCI.

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Aquaporin water channels in the nervous system

Cited by 617 publications

References 158 publications

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

A Comparison of Clinical Presentation and MRI Findings in Neuromyelitis optica Spectrum Disorder and Spinal Cord Infarct in Complex Patients with Multiple Co-Morbidities

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