scholarly journals Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jacek Szczygielski ◽  
Marta Kopańska ◽  
Anna Wysocka ◽  
Joachim Oertel

In the past, water homeostasis of the brain was understood as a certain quantitative equilibrium of water content between intravascular, interstitial, and intracellular spaces governed mostly by hydrostatic effects i.e., strictly by physical laws. The recent achievements in molecular bioscience have led to substantial changes in this regard. Some new concepts elaborate the idea that all compartments involved in cerebral fluid homeostasis create a functional continuum with an active and precise regulation of fluid exchange between them rather than only serving as separate fluid receptacles with mere passive diffusion mechanisms, based on hydrostatic pressure. According to these concepts, aquaporin-4 (AQP4) plays the central role in cerebral fluid homeostasis, acting as a water channel protein. The AQP4 not only enables water permeability through the blood-brain barrier but also regulates water exchange between perivascular spaces and the rest of the glymphatic system, described as pan-cerebral fluid pathway interlacing macroscopic cerebrospinal fluid (CSF) spaces with the interstitial fluid of brain tissue. With regards to this, AQP4 makes water shift strongly dependent on active processes including changes in cerebral microcirculation and autoregulation of brain vessels capacity. In this paper, the role of the AQP4 as the gatekeeper, regulating the water exchange between intracellular space, glymphatic system (including the so-called neurovascular units), and intravascular compartment is reviewed. In addition, the new concepts of brain edema as a misbalance in water homeostasis are critically appraised based on the newly described role of AQP4 for fluid permeation. Finally, the relevance of these hypotheses for clinical conditions (including brain trauma and stroke) and for both new and old therapy concepts are analyzed.

Neurology ◽  
2018 ◽  
Vol 91 (11) ◽  
pp. 515-522 ◽  
Author(s):  
Stéphanie Lenck ◽  
Ivan Radovanovic ◽  
Patrick Nicholson ◽  
Mojgan Hodaie ◽  
Timo Krings ◽  
...  

The recent discoveries of the glymphatic and lymphatic systems of the brain have helped advance our understanding of CSF physiology and may allow new insights in the understanding of idiopathic intracranial hypertension (IIH). The clinical and radiologic presentations of IIH appear to be related to congestion of the glymphatic system associated with an overflow of the lymphatic CSF outflow pathway. By revisiting the role of “vascular arachnoid granulations” in the brain, we hypothesize that an initial impairment of the transport of interstitial fluid from the glymphatic system to the venous blood of the dural sinuses may trigger the hydrodynamic cascade of IIH. Furthermore, we speculate that, similar to other water-exchange systems in the brain, a specific subtype of aquaporin is involved in this transport. This theory may eventually help to provide an underlying explanation for IIH and its associated conditions, since in most of them, the expression of several aquaporins is altered.


2016 ◽  
Vol 41 (3) ◽  
pp. E8 ◽  
Author(s):  
Bhargav Desai ◽  
Ying Hsu ◽  
Benjamin Schneller ◽  
Jonathan G. Hobbs ◽  
Ankit I. Mehta ◽  
...  

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.


2020 ◽  
Author(s):  
Xiaosong Liu ◽  
Yingxin Xie ◽  
Xiangdong Wan ◽  
Jianliang Wu ◽  
Zhenzeng Fan ◽  
...  

Abstract Background: Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear.Methods: AQP4−/− and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Morris water maze (MWM) was used to establish the cognitive functions of AQP4−/− and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay.Results: AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation.Conclusion: AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.


2016 ◽  
Vol 33 (4) ◽  
pp. 522-568
Author(s):  
Cory M. Gavito

Among the roughly 150 Italian songbooks published between 1610 and 1665 with the guitar tablature known as alfabeto, about thirteen are anthologies. These anthologies often advertise the role of a compiler who has gathered together music by diverse authors. The extent to which compilers also functioned as authors and editors is not well understood. This essay considers the case of Giovanni Stefani, a compiler who, in the preface to his Scherzi amorosi of 1622, describes the anthology as a collection of his choosing that contains “varie compositioni de Virtuosi della prima classe” (various compositions of first-class virtuosos). Intriguingly, none of the settings Stefani prints (in both this alfabeto anthology and two others) include attributions. Since the 1880s, scholars have been preoccupied with matters of transmission and attribution, unearthing a network of textual and musical concordances. This article expands the nexus of Stefani’s songs and their concordant sources, revealing an array of examples that range from identical copies to “partial” concordances that take over motives, phrases, refrains, or harmonic schemes. These examples indicate that in preparing his anthologies, Stefani mined a corpus of existing prints and manuscripts while also relying heavily on oral transmission. The complex nature of Stefani’s approach, taken together with his complete avoidance of composer attributions, points toward an editorial process shaped by a fluid exchange between oral and written musical practices.


Author(s):  
Junyuan Wu ◽  
Zhiwei Li ◽  
Wei Yuan ◽  
Qiang Zhang ◽  
Yong Liang ◽  
...  

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.


PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218415 ◽  
Author(s):  
Yifan Zhang ◽  
Kui Xu ◽  
Yuchi Liu ◽  
Bernadette O. Erokwu ◽  
Pan Zhao ◽  
...  

Water exchange between insects and their environment via the vapour phase includes influx and efflux components. The pressure cycle theory postulates that insects (and some other arthropods) can regulate the relative rates of influx and efflux of water vapour by modulating hydrostatic pressures at a vapour-liquid interface by compressing or expanding a sealed, gas-filled cavity. Some such cavities, like the tracheal system, could be compressed by elevated pressure in all or part of the haemocoele. Others, perhaps including the muscular rectum of flea prepupae, could be compressed by intrinsic muscles. Maddrell Insect Physiol . 8, 199 (1971)) suggested a pressure cycle mechanism of this kind to account for rectal uptake of water vapour in Thermobia but did not find it compatible with quantitative information then available. Newer evidence conforms better with the proposed mechanism. Cyclical pressure changes are of widespread occurrence in insects and have sometimes been shown to depend on water status. Evidence is reviewed for the role of the tracheal system as an avenue for net exchange of water between the insect and its environment. Because water and respiratory gases share common pathways, most published findings fail to distinguish between the conventional view that the tracheal system has evolved as a site for distribution and exchange of respiratory gases and that any water exchange occurring in it is generally incidental and nonadaptive, and the theory proposed here. The pressure cycle theory offers a supplementary explanation not incompatible with evidence so far available. The relative importance of water economy and respiratory exchange in the functioning of compressible cavities such as the tracheal system remains to be explored. Some further implications of the pressure cycle theory are discussed. Consideration is given to the possible involvement of vapour-phase transport in the internal redistribution of water within the body. It is suggested that some insect wings may constitute internal vapour-liquid exchange sites, where water can move from the body fluids to the intratracheal gas. Ambient and body temperature must influence rates of vapour-liquid mass transfer. If elevated body temperature promotes evaporative discharge of the metabolic water burden that has been shown to accumulate during flight in some large insects, their minimum threshold thoracic temperature for sustained flight may relate to the maintenance of water balance. The role of water economy in the early evolution of insect wings is considered. Pressure cycles might help to maintain water balance in surface-breathing insects living in fresh and saline waters, but the turbulence of the surface of the open sea might prevent truly marine forms from using this mechanism.


1998 ◽  
Vol 78 (1) ◽  
pp. 53-97 ◽  
Author(s):  
FRANK M. FARACI ◽  
DONALD D. HEISTAD

Faraci, Frank M., and Donald D. Heistad. Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiol. Rev. 78: 53–97, 1998. — Several new concepts have emerged in relation to mechanisms that contribute to regulation of the cerebral circulation. This review focuses on some physiological mechanisms of cerebral vasodilatation and alteration of these mechanisms by disease states. One mechanism involves release of vasoactive factors by the endothelium that affect underlying vascular muscle. These factors include endothelium-derived relaxing factor (nitric oxide), prostacyclin, and endothelium-derived hyperpolarizing factor(s). The normal vasodilator influence of endothelium is impaired by some disease states. Under pathophysiological conditions, endothelium may produce potent contracting factors such as endothelin. Another major mechanism of regulation of cerebral vascular tone relates to potassium channels. Activation of potassium channels appears to mediate relaxation of cerebral vessels to diverse stimuli including receptor-mediated agonists, intracellular second messengers, and hypoxia. Endothelial- and potassium channel-based mechanisms are related because several endothelium-derived factors produce relaxation by activation of potassium channels. The influence of potassium channels may be altered by disease states including chronic hypertension, subarachnoid hemorrhage, and diabetes.


1996 ◽  
Vol 2 (12) ◽  
pp. 1607-1615 ◽  
Author(s):  
Éva Tóth ◽  
Dirk Pubanz ◽  
Sylvain Vauthey ◽  
Lothar Helm ◽  
André E. Merbach

2017 ◽  
Vol 886 ◽  
pp. 012002 ◽  
Author(s):  
D Atochin ◽  
M Litvak ◽  
S Huang ◽  
Y R Kim ◽  
P Huang

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