Hypoxia‐induced astrocytic reaction and increased vascular permeability in the rat cerebellum

Kaur, Charanjit; Sivakumar, V.; Zhang, Y.; Ling, Eng‐Ang

doi:10.1002/glia.20420

Cited by 155 publications

(150 citation statements)

References 51 publications

(53 reference statements)

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“…Statistical analysis is referred to levels of ␤-actin expression. *, p Ͻ 0.05; **, p Ͻ 0.01; ***, p Ͻ 0.001. cells the AQP-5 gene is up-regulated by HIF through interaction with hypoxia-responsive elements in the promoter (40), and AQP-4 mRNA has also been shown to be up-regulated by hypoxia in astrocytes (41). This could explain why humans (14) and mice (12,13) lacking AQP-1 do not exhibit major gross physiological alterations related with either water or O 2 metabolism.…”

Section: Discussionmentioning

confidence: 99%

Development of Cytosolic Hypoxia and Hypoxia-inducible Factor Stabilization Are Facilitated by Aquaporin-1 Expression

Echevarría

Muñoz-Cabello

Sánchez-Silva

et al. 2007

Journal of Biological Chemistry

113

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O 2 is essential for aerobic life, and the classic view is that it diffuses freely across the plasma membrane. However, measurements of O 2 permeability of lipid bilayers have indicated that it is much lower than previously thought, and therefore, the existence of membrane O 2 channels has been suggested. We hypothesized that, besides its role as a water channel, aquaporin-1 (AQP-1) could also work as an O 2 transporter, because this transmembrane protein appears to be CO 2 -permeable and is highly expressed in cells with rapid O 2 turnover (erythrocytes and microvessel endothelium). Here we show that in mammalian cells overexpressing AQP-1 and exposed to hypoxia, the loss of cytosolic O 2 , as well as stabilization of the O 2 -dependent hypoxia-inducible transcription factor and expression of its target genes, is accelerated. In normoxic endothelial cells, knocking down AQP-1 produces induction of hypoxiainducible genes. Moreover, lung AQP-1 is markedly up-regulated in animals exposed to hypoxia. These data suggest that AQP-1 has O 2 permeability and thus could facilitate O 2 diffusion across the cell membrane.Oxygen (O 2 ) is necessary for aerobic life because of its central role in mitochondrial ATP synthesis by oxidative phosphorylation. Traditionally, O 2 is considered to diffuse freely across the plasma membrane (1, 2); however, recent studies have shown that O 2 permeability of lipid bilayers is some orders of magnitude lower than previously thought (3). Therefore, it has been suggested that there exist yet unknown plasmalemmal O 2 channels to ensure the fluxes required for O 2 uptake in conditions of high demand or limited O 2 availability. Good candidates are aquaporins, widely distributed intrinsic membrane proteins that form water-permeable complexes (3, 4). Mammalian aquaporin-1 (AQP-1) 4 is highly expressed in cells with rapid gas (O 2 /CO 2 ) turnover such as erythrocytes (5) and microvessel endothelium (6, 7), and experiments performed with recombinant AQP-1 expressed in Xenopus oocytes have suggested that it confers upon the cells increased membrane CO 2 permeability (8 -10). In addition, it has been shown that the AQP-1 tobacco plant homolog Nt-AQP-1 facilitates CO 2 transport, particularly in conditions of small transmembrane CO 2 gradient, and has a significant function in photosynthesis and in stomatal opening (11). Against a possible role of AQP-1 as a gas channel is that AQP-1 null mice do not show any obvious sign of respiratory distress or alteration of lung or erythrocyte CO 2 transport (12, 13). This observation could, however, be explained if other aquaporins can compensate, at least partially, for the lack of AQP-1. In fact, AQP-1 functions as a well established water channel, but AQP-1 null humans (Colton-null blood group) (14) and AQP-1-deficient mice (12) have only subtle changes of erythrocyte water diffusion or renal urine concentration. A recent study shows that after subcutaneous or intracranial malignant cell implantation, AQP-1 null animals present impaired tumor growth and v...

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Section: Discussionmentioning

confidence: 99%

Development of Cytosolic Hypoxia and Hypoxia-inducible Factor Stabilization Are Facilitated by Aquaporin-1 Expression

Echevarría

Muñoz-Cabello

Sánchez-Silva

et al. 2007

Journal of Biological Chemistry

113

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“…15 A recent study in rats demonstrated that under hypoxic conditions, upregulation of HIF1a was associated with AQP4 increase in the brain, and that HIF-1a inhibitor can benefit neurological outcomes by reducing water content or brain swelling rates with downregulation of AQP4. [36][37][38] Cigarette smoke exposure can upregulate water content and AQP4 expression, which is likely triggered by HIF-1a.…”

Section: Figmentioning

confidence: 99%

The Effect of Cigarette Smoke Exposure on Spinal Cord Injury in Rats

Fan

Cao

et al. 2013

Journal of Neurotrauma

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In this study, we examined whether cigarette smoke has neuroprotective or toxic effects on spinal cord injury (SCI). Male Sprague-Dawley rats were included in the study and received either cigarette smoke exposure or fresh air exposure. Twenty-four hours after the last cigarette smoke or fresh air exposure, all rats were injured at thoracic level 12 (T12), using an established static compression model. Our data showed that the cigarette smoke group had higher water content; higher permeability of the blood-spinal cord barrier (BSCB); higher malondialdehyde (MDA) levels, aquaporin-4 (AQP4) and hypoxia-inducible factor 1-alpha (HIF-1a) protein expression, and mRNA levels; and lower glutathione (GSH) levels than the control group values at 12 h, 24 h, and 48 h after SCI. There was no significant difference in these between the cigarette smoke group and the control group at 0 h after SCI. The results of the Basso, Beattie, and Bresnahan (BBB) hindlimb locomotor rating scale showed that rats in the cigarette smoke group had greater dysfunction in hindlimb movement than did rats in control group from 2 to day 6 after SCI. The extent of recovery did not make any difference from day 7 to day 10 after SCI between the cigarette smoke group and the control group. These results suggested that cigarette smoke can reinforce the oxidative stress injury via HIF-1a and AQP4 in the early stage after SCI. It is possible that cigarette smoke exposure does not affect SCI recovery in the long term; however, it can aggravate the edema and deteriorate BSCB disruption via HIF-1a and AQP4 in the early stage after SCI. More studies will be essential to consider this hypothesis and elucidate the mechanisms involved.

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“…However, other contributory factors could include increased expression of the aquaporin 4 water channel in astrocytes (30), and downregulation of angiopoietin-1, an important accessory protein for neovascularization and producing stable blood vessel structure, which is also correlated with increased blood-brain barrier leakage (31).…”

Section: Microvasculature and Fetal Hypoxiamentioning

confidence: 99%

VEGF expression and microvascular responses to severe transient hypoxia in the fetal sheep brain

2012

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Background: Fetal hypoxia contributes significantly to the pathogenesis of permanent perinatal brain injury. We hypothesized that hypoxia-induced cerebral angiogenesis and microvascular changes would occur in fetal sheep subjected to a severe hypoxic insult produced by umbilical cord occlusion (UcO) for 10 min. Methods: at 124-126 d of gestation, singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. a 10-min UcO or sham UcO (n = 5) was induced at 130 d gestation. The fetal brain was collected at 24 h (n = 5) or 48 h (n = 4) after UcO for immunohistochemical analysis of vascular endothelial growth factor (VeGF), Ki67, and serum albumin. results: By 48 h after UcO, the percentage of blood vessels expressing VeGF had increased in the subventricular zone, periventricular and subcortical white matter, corpus callosum, and cortex. alterations in vascular permeability (albumin extravasation) were observed only in the periventricular and subcortical white matter and the subventricular zone following UcO. conclusion: The upregulation of VeGF expression and increased leakage of plasma protein in the fetal sheep brain show that the microvasculature in white matter is sensitive to hypoxia in the near-term brain.

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Hypoxia‐induced astrocytic reaction and increased vascular permeability in the rat cerebellum

Cited by 155 publications

References 51 publications

Development of Cytosolic Hypoxia and Hypoxia-inducible Factor Stabilization Are Facilitated by Aquaporin-1 Expression

Development of Cytosolic Hypoxia and Hypoxia-inducible Factor Stabilization Are Facilitated by Aquaporin-1 Expression

The Effect of Cigarette Smoke Exposure on Spinal Cord Injury in Rats

VEGF expression and microvascular responses to severe transient hypoxia in the fetal sheep brain

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