Aquaporin 4 changes in rat brain with severe hydrocephalus

Mao, Xiaoyan; Enno, Terry L.; Bigio, Marc R. Del

doi:10.1111/j.1460-9568.2006.04829.x

Cited by 84 publications

(85 citation statements)

References 78 publications

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“…AQP4, the most abundant water channel in the brain, is expressed in astrocytes, particularly in the end feet, and promotes water clearance from swelling cells (39). Increased expression of AQP4 in the brain is associated with cerebral edema and related neurological disorders (40)(41)(42)(43), and AQP4-deficient mice survive better than wild-type mice in a model of brain edema (41).…”

Section: Discussionmentioning

confidence: 99%

Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

Chen

Yang

Kong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca 2+, and PKCe; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1+ and AQP4 + , we show that transfected CRFR1+ contributes to edema via transfected AQP4 + . In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema.water permeability | high altitude | acute mountain sickness A pproximately 140 million people around the world live at altitudes of >2,500 m, including >8 million who live on the Qinghai-Tibet plateau of China at an average elevation of >4,000 m. Living at these altitudes requires physiological adaptations to compensate for the lower partial pressure of oxygen (1). In travelers who ascend to altitudes too high or too quickly (2-4) or in people with fatigue and infection or psychological stress (3, 4), hypoxia can induce acute mountain sickness (AMS) that can develop into high-altitude cerebral edema (HACE), a serious and often fatal condition (2-6). Today's ability to travel rapidly to high altitudes means that, every year, millions of people are exposed to the risk of AMS and HACE (7).In human volunteers exposed for 32 h to hypobaric hypoxia (corresponding to 4,572 m altitude), brain volume increases by 2.77% (8), whereas normobaric hypoxia (12% O 2 , corresponding to a simulated altitude of 4,500 m) for 16 h produces 50% AMS, headache, a mild increase in brain volume, and cytotoxic cerebral edema (9). A recent study reported that seven of nine male students exposed to isobaric hypoxia (inhaled room air enriched with N 2 for 6 h to obtain arterial saturation values of 75-80%) developed AMS; the mean apparent diffusion coefficient (ADC) increased by 2.12% in these subjects, indicating mild extracellular (vasogenic) cerebral edema. The ADC changes were negatively correlated with AMS scores, suggesting that severe AMS is associated with intracellular (cytotoxic) cerebral edema in addition to vasogenic edema (10).In parallel with the increasing brain water content, hypoxia acutely activates the hypothalamic-pituitary-adrenal axis in rats (11-13), increasing corticotropin-releasing factor (CRF) and endothelin-1 (ET-1)...

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Section: Discussionmentioning

confidence: 99%

Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

Chen

Yang

Kong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Increased expression of AQP4 or Aqp4 mRNA has been found in numerous conditions, including bacterial meningitis (141), inflammation secondary to intraparenchymal injection of lipopolysaccharides (LPS) (187) or lysolecithin (190), subarachnoid hemorrhage (198), intracerebral hemorrhage (182), brain tumors (32,135,164), and hydrocephalus (100,144,168,170,189). It is still not known whether changes in surface expression of AQP4 occur under physiological conditions.…”

Section: Regulationmentioning

confidence: 99%

Physiological Roles of Aquaporin-4 in Brain

Nagelhus

Ottersen

2013

Physiological Reviews

596

520

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(AQP4) is one of the most abundant molecules in the brain and is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. While AQP4 has been implicated in a number of pathophysiological processes, its role in brain physiology has remained elusive. Only recently has evidence accumulated to suggest that AQP4 is involved in such diverse functions as regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, interstitial fluid resorption, waste clearance, neuroinflammation, osmosensation, cell migration, and Ca 2ϩ signaling. AQP4 is also required for normal function of the retina, inner ear, and olfactory system. A review will be provided of the physiological roles of AQP4 in brain and of the growing list of data that emphasize the polarized nature of astrocytes.

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“…42 In contrast, ependymal AQP4 is upregulated in the late stages of hydrocephalus, possibly as a compen-satory mechanism to maintain water homeostasis. 19,86 In addition, it has been well documented that the ependymal cells lining the ventricular space have motile cilia and that defects in motile cilia lead to hydrocephalus. 6,84 Mice with mutations in the cilia proteins Spag6 or hydin, or the transcription factor Hfh4 (Foxj1, Mouse Genome Informatics) that lack ependymal cell cilia all exhibit hydrocephalus.…”

Section: Hydrocephalus and Csf Productionmentioning

confidence: 99%

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

Karimy¹,

Durán²,

Hu³

et al. 2016

FOC

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Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

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Aquaporin 4 changes in rat brain with severe hydrocephalus

Cited by 84 publications

References 78 publications

Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

Physiological Roles of Aquaporin-4 in Brain

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

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