Expression of Water Channel mRNA Following Cerebral Ischemia

Sato, Seiji; Umenishi, Fuminori; Inamasu, G.; Sato, Minako; Ishikawa, M.; Nishizawa, Mikio; Oizumi, Taro

doi:10.1007/978-3-7091-6346-7_48

Cited by 28 publications

(19 citation statements)

References 16 publications

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“…We found that SCI induces both early down-regulation and late up-regulation of AQP4. Similar observations were reported in brain ischemic models; AQP4 was reduced within the first 48 h after onset (Sato et al, 2000;Yamamoto et al, 2001) while marked upregulation occurs at later time points (Taniguchi et al, 2000).…”

Section: Sci-induced Changes In Aqp4 Expressionsupporting

confidence: 86%

Acute and chronic changes in aquaporin 4 expression after spinal cord injury

et al. 2006

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The effect of spinal cord injury (SCI) on the expression levels and distribution of water channel aquaporin 4 (AQP4) has not been studied. We have found AQP4 in gray and white matter astrocytes in both uninjured and injured rat spinal cords. AQP4 was detected in astrocytic processes that were tightly surrounding neurons and blood vessels, but more robustly in glia limitans externa and interna, which were forming an interface between spinal cord parenchyma and cerebrospinal fluid (CSF). Such spatial distribution of AQP4 suggests a critical role that astrocytes expressing AQP4 play in the transport of water from blood/CSF to spinal cord parenchyma and vice versa. SCI induced biphasic changes in astrocytic AQP4 levels, including its early down-regulation and subsequent persistent up-regulation. However, changes in AQP4 expression did not correlate well with the onset and magnitude of astrocytic activation, when measured as changes in GFAP expression levels. It appears that reactive astrocytes began expressing increased levels of AQP4 after migrating to the wound area (thoracic region) two weeks after SCI, and AQP4 remained significantly elevated for months after SCI. We also showed that increased levels of AQP4 spread away from the lesion site to cervical and lumbar segments, but only in chronically injured spinal cords. Although overall AQP4 expression levels increased in chronically-injured spinal cords, AQP4 immunolabeling in astrocytic processes forming glia limitans externa was decreased, which may indicate impaired water transport through glia limitans externa. Finally, we also showed that SCI-induced changes in AQP4 protein levels correlate, both temporally and spatially, with persistent increases in water content in acutely and chronically injured spinal cords. Although correlative, this finding suggests a possible link between AQP4 and impaired water transport/edema/syringomyelia in contused spinal cords.

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Section: Sci-induced Changes In Aqp4 Expressionsupporting

confidence: 86%

Acute and chronic changes in aquaporin 4 expression after spinal cord injury

et al. 2006

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“…After transient focal brain ischemia in mice, two peaks of maximal hemispheric swelling at 1 h and at 48 h post-ischemia coincided with two peaks of AQP4 expression (Ribeiro Mde et al, 2006). Following experimental cerebral ischemia in the rat, AQP4 mRNA levels have been reported to be decreased at 24 h in ischemic compared to non-ischemic hemispheres (Sato et al, 2000), while in another study, researchers found AQP4 mRNA to be increased in the peri-infarcted area, and it peaked on day 3 (Taniguchi et al, 2000). In experimental traumatic brain injury (TBI) in the rat, AQP4 mRNA was increased at the injury site in a cortical contusion model at 24 h , whereas in another study AQP4 mRNA was decreased in edematous contusional cortex with impaired BBB integrity (Ke et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The specific anatomical and cellular localization of aquaporin 4 (AQP 4) water channels in the central nervous system suggests that this protein plays a crucial role in the cerebral water balance . Recently, the role of AQP4 in maintaining water homeostasis during the development of post-traumatic or ischemic brain edema has been described, although conflicting results have been obtained using different models (Hu et al, 2005;Ke et al, 2001;Kiening et al, 2002;Lu and Sun, 2003;Manley et al, 2000;Meng et al, 2004;Sato et al, 2000;Sun et al, 2003;Taniguchi et al, 2000;Vizuete et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The Protein Kinase C Activator Phorbol Myristate Acetate Decreases Brain Edema by Aquaporin 4 Downregulation after Middle Cerebral Artery Occlusion in the Rat

Fazzina

Amorini

Marmarou

et al. 2010

Journal of Neurotrauma

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The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) is known to interact with aquaporin 4 (AQP 4), a water-selective transporting protein that is abundant in astrocytes, and has experimentally been found to decrease osmotically-induced cell swelling. The purpose of this study was to examine whether PMA reduces brain edema following focal ischemia induced by middle cerebral artery (MCA) occlusion by modulation of AQP4 expression. Male Sprague-Dawley rats were randomly assigned to either sham surgery (n ¼ 6), or a continuous intravenous infusion of vehicle (1% dimethylsulfoxide), followed by MCA occlusion (n ¼ 18), and administration of PMA at 50 mg=kg (n ¼ 6) or at 200 mg=kg (n ¼ 6) starting 60 min before or 30 min (200 mg=kg; n ¼ 6) or 60 min (200 mg=kg; n ¼ 6) after MCA occlusion. Cerebral blood flow was monitored with laser Doppler over the MCA territory, and confirmed a 70% reduction during occlusion. After a 2-h period of ischemia and 2 h of reperfusion, the animals were sacrificed for assessment of brain water content and sodium and potassium concentration. AQP4 expression was assessed by immunoblotting and quantified by densitometry (n ¼ 24). Statistical analysis was performed by ANOVA followed by Tukey's post-hoc test. PMA treatment at 200 mg=kg significantly reduced brain water concentration in the infarcted area when started 60 min before or 30 min after occlusion ( p < 0.001 and p ¼ 0.022, respectively), and prevented the subsequent sodium shift ( p < 0.05). PMA normalized the AQP4 upregulation in ischemia ( p ¼ 0.021). A downregulation of AQP4 in the ischemic area paralleling the reduction in brain edema formation following PMA treatment suggests that the effect was mediated by AQP4 modulation.

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“…Sato et al demonstrated in a rat model of permanent focal cerebral ischemia that AQP4 mRNA expression was slightly decreased at 30 minutes and six hours and remarkably decreased at 24 hours after ischemia. 25 In rats subjected to traumatic brain injury, AQP4 protein and mRNA expressions were decreased along with traumatic brain edema at 24 hours of injury. 9,23 The reasons for the discrepancy in the expression of AQP4 in the brain between these studies and the present study are not clear.…”

Section: Discussionmentioning

confidence: 95%

“…[20][21][22] Several studies have shown a key role of AQP4 in the development of brain edema in animal models of brain tumor, acute water intoxication, focal cerebral I/R, and traumatic brain injury. 6,7,9,[23][24][25][26] However, little is known about the role of AQP4 in the development of brain edema caused by CA.…”

Section: Discussionmentioning

confidence: 99%