Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Edema formation can be observed using magnetic resonance imaging (MRI) in patients with stroke. Recent studies have shown that aquaporin-4 (AQP4), a water channel, is induced early after stroke and potentially participates in the development of brain edema. We studied whether induction of AQP4 correlated with edema formation in a rat pup filament stroke model using high field (11.7-Tesla) MRI followed by immunohistochemical investigation of AQP4 protein expression. At 24 h, we observed increased T2 values and decreased apparent diffusion coefficients (ADC) within injured cortical and striatal regions that reflected the edema formation. Coincident with these MR changes were significant increases in AQP4 expression on astrocytic end-feet in the border regions of injured tissues. Striatal imaging findings were still present at 72 h with a slow normalization of AQP4 expression in the border regions. At 28 d, AQP4 expression normalized in the border while in this region ADC values increased. We show that induction of AQP4 is increased during the period of active edema formation in the border region without regional correlation with edema. Finally, induction of AQP4 on astrocyte end-feet could participate in tissue preservation after ischemia in the immature rat brain.
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PMID:Temporal and regional evolution of aquaporin-4 expression and magnetic resonance imaging in a rat pup model of neonatal stroke. 1762 64

Previous RT-PCR experiments revealed the expression of gene transcripts for a variety of aquaporins in the neural retina, including aquaporin-0. We investigated by immunohistochemistry and Western blotting whether the aquaporin-0 protein is expressed in the retina of the rat. In addition to the lens, immunoreactivity for aquaporin-0 was expressed in the neural retina, but was absent in the pigment epithelium, choroidea, and sclera. In the neural retina, aquaporin-0 immunoreactivity was expressed by the nuclei and the synaptic terminals of protein kinase alpha- and beta-expressing bipolar and amacrine cells, and by the nuclei of neuronal cells in the ganglion cell layer. The immunoreactivity for aquaporin-0 did not co-localize with calbindin, a marker of horizontal cells, or with aquaporin-4, the glial water channel. Transient retinal ischemia caused a slight decrease in the retinal content of aquaporin-0, likely by degeneration of protein kinase alpha-expressing bipolar cells. It is concluded that aquaporin-0 may be involved in the regulation of the activity of retinal second order neurons.
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PMID:Localization of aquaporin-0 immunoreactivity in the rat retina. 1788 Nov 23

Stroke is the third leading cause of death and the leading cause of adult disability in the industrialized nations. One of the consequences of stroke is blood-brain barrier (BBB) leakage and subsequent edema, which is one of the causes of mortality in this pathology. Aquaporin-4 (AQP4) is the most abundant water channel in the brain. Studies in AQP4 knock-out mice have shown a prominent role of this water channel in edema development and resolution after ischemia. Here we have studied changes in AQP4 mRNA and protein expression in response to vascular endothelial growth factor (VEGF), a potent angiogenic factor. VEGF administration highly upregulated AQP4 mRNA and protein in the ventral midbrain. Perfusion of the animals with FITC-albumin prior to sacrifice demonstrated localization of AQP4 protein in close proximity to the VEGF-induced new blood vessels. Expression levels of AQP4 mRNA were maximum 7 days after VEGF injection whereas our previous report showed that BBB leakage is resolved at this time point. Therefore, we speculate a positive role of AQP4 in edema resolution, which may partially explain the previously reported beneficial effects of delayed VEGF administration in ischemic rats. Our results provide new insights into the molecular changes in the edematous brain and may help in future therapeutical directions.
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PMID:Intracerebral VEGF injection highly upregulates AQP4 mRNA and protein in the perivascular space and glia limitans externa. 1802 90

Aquaporin-4 (AQP4) has been shown to be important in the evolution of stroke-associated cerebral edema. However, the role of AQP4 in stroke-associated cerebral edema as it pertains to sex has not been previously studied. The perivascular pool of AQP4 is important in the influx and efflux of water during focal cerebral ischemia. We used mice with targeted disruption of the gene encoding alpha-syntrophin (alpha-Syn(-/-)) that lack the perivascular AQP4 pool but retain the endothelial pool of this protein. Infarct volume at 72 h after transient focal ischemia (90 mins) in isoflurane-anesthetized mice was attenuated in both sexes with alpha-Syn deletion as compared with their wild-type (WT) counterparts. There were no sex differences in hemispheric water content in WT and alpha-Syn(-/-) mice or regional AQP4 expression in WT mice. In neither sex did alpha-Syn deletion lead to alterations in end-ischemic regional cerebral blood flow (rCBF). These data suggest that after experimental stroke: (1) there is no difference in stroke-associated cerebral edema based on sex, (2) AQP4 does not involve in sex-based differences in stroke volume, and (3) perivascular pool of AQP4 has no significant role in end-ischemic rCBF.
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PMID:Lack of sex-linked differences in cerebral edema and aquaporin-4 expression after experimental stroke. 1864 81

The study investigated whether bradykinin (BK) preconditioning could regulate the expression of aquaporin-4 (AQP4) using an in vivo transient spinal cord ischemia model in rats. BK was infused continuously via the left femoral artery with infusion pump for 15 min (10 microg/kg/min) then we induced ischemia for 20 min and reperfusion for 24 and 72 h respectively. The results demonstrated that the central part of the white matter exhibited loss of perivascular AQP4 and showed a partial recovery toward 72 h of reperfusion. The border zone of white matter was different from the central part of the white matter by showing no loss of perivascular AQP4 at 24 h of reperfusion but rather a slight increase. BK significantly reduced the expression level of AQP4 protein in the white matter, but it had none of this effect in the gray matter region at 72 h post-reperfusion. There was no difference in AQP4 protein levels between BK group and control group at the two above-mentioned spinal cord regions at 24 h after reperfusion. In addition, the changes in AQP4 protein induced by BK preconditioning were obvious at 72 h after reperfusion, which were accompanied by a reduction of spinal cord edema. Our results demonstrated that the expression of AQP4 protein after spinal cord ischemia/reperfusion was region-specific, time-dependent and also indicated that the attenuation of AQP4 expression induced by BK could be one of the important molecular mechanisms in physiopathology of spinal cord ischemic edema.
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PMID:Bradykinin preconditioning modulates aquaporin-4 expression after spinal cord ischemic injury in rats. 1895 83

Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechanism of brain water transport and edema formation remain poorly understood. As a result, current therapeutic tools for managing cerebral edema have changed little in the past 90 years. "Malignant ischemic stroke" is characterized by high mortality (80%) and represents a major clinical problem in cerebrovascular disease. Widespread ischemic injury in these patients causes progressive cerebral edema, increased ICP, and rapid clinical decline. In response to these observations, a series of recent studies have begun to target cerebral edema in the management of large ischemic strokes. During cerebral edema formation, the glial water channel aquaporin-4 (AQP4) has been show to facilitate astrocyte swelling ("cytotoxic swelling"). AQP4 has also been seen to be responsible for the reabsorption of extracellular edema fluid ("vasogenic edema"). In the present review, the role of AQP4 in the development of cerebral edema is discussed with emphasis on its contribution to ischemic edema. We also examine the potential of AQP4 as a therapeutic target in edema associated with stroke.
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PMID:Role of aquaporin-4 in cerebral edema and stroke. 1909 76

Aquaporin-4 (AQP4) has been implicated in cytotoxic brain edema resulting from water intoxication, brain ischemia or meningitis. AQP4 inhibitors suitable for clinical use would thus be expected to help protect against brain edema. Here, we report the effect of inhibitors on water conduction by AQP4 and AQP1 reconstituted into liposomes. Acetazolamide (AZA), an inhibitor of sulfonamide carbonic anhydrase (CA), reversibly inhibits water permeation through AQP4, but not through AQP1. Methazolamide (MZA), another sulfonamide CA inhibitor similar in chemical structure to AZA, shows no significant effect on water conduction by AQP4 or AQP1. Our results thus demonstrate that AZA acts as a reversible inhibitor for AQP4-mediated water conduction and indicate that AZA is specific, at least to some degree, for AQP4. AZA may thus serve as a lead compound for the development of AQP4-specific inhibitors for clinical applications.
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PMID:Acetazolamide reversibly inhibits water conduction by aquaporin-4. 1911 9

The study was performed to investigate whether the ischemic gray matter and white matter show distinct patterns of aquaporin-4 (AQP4) expression in the reperfusion phase using an in-vivo transient spinal cord ischemia model in rats. We investigated to the time course of AQP4 expression at the blood-spinal cord interface by the quantitative immunogold and western blots methods. The results showed that disruption of AQP4 anchoring at the perivascular membrane did not lead to a net loss of protein. This is the first systematic and extensive study fully showing AQP4 expression dynamics after transient spinal cord ischemia and the findings are of major clinical and experimental interest.
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PMID:Temporary loss of perivascular aquaporin-4 in white matter after the spinal cord ischemic injury of rats. 2000 10

The cerebral ischemia-reperfusion injury remains a major medical problem due to the lack of effective treatment. The mechanism of brain injury is still unknown. The defensive and offensive factors, such as platelet-derived growth factor-BB (PDGF-BB), 5-lipoxygenase (5-LO), aquaporin-4 (AQP-4) and insulin-like growth factor-1 (IGF-1) may play important roles. So far, only individual factors were reported. What are the relationships among them in brain ischemia-reperfusion injury remains obscure. The present study is to investigate simultaneously the expression of PDGF-BB, 5-LO, AQP-4 and IGF-1 in middle cerebral artery occlusion/reperfusion (MCAO/R) in rats. We found that 5-LO and IGF-1 reached the peak level at 24h after reperfusion, AQP-4 at 72 h and PDGF-BB at 7 days. With these results we inferred that both defensive factors, such as PDGF-BB, AQP-4 and IGF-1, and offensive factor, like 5-LO, play some roles in the ischemia-reperfusion injury.
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PMID:Longitudinal changes of defensive and offensive factors in focal cerebral ischemia-reperfusion in rats. 1944 8

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.
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PMID:Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. 1973 35


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