Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

Han, Xinjia; Huang, Qian; Liu, Lei; Sha, Xiaoyan; Hu, Bihui; Liu, Huishu

doi:10.3390/ijms19010300

Cited by 15 publications

(7 citation statements)

References 41 publications

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“…Consistent with the present findings, our previous study showed that KA treatment increases the number of AQP4-positive astrocytes in the hippocampus [40]. In another study, AQP4 mRNA and protein levels in the hippocampus were significantly upregulated after eclampsia-like seizures [45]. Ex-4 attenuated all symptoms of BBB leakage, indicating that Ex-4 stabilized KA-induced BBB breakdown.…”

Section: Discussionsupporting

confidence: 92%

Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death

Ahn

Shin

Jeong

et al. 2021

Cells

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Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that protects against brain injury. However, little is known about the effect of Ex-4 on kainic acid (KA)-induced seizures and hippocampal cell death. Therefore, this study evaluated the neuroprotective effects of Ex-4 pretreatment in a mouse model of KA-induced seizures. Three days before KA treatment, mice were intraperitoneally injected with Ex-4. We found that Ex-4 pretreatment reversed KA-induced reduction of GLP-1R expression in the hippocampus and attenuated KA-induced seizure score, hippocampal neuronal death, and neuroinflammation. Ex-4 pretreatment also dramatically reduced hippocampal lipocalin-2 protein in KA-treated mice. Furthermore, immunohistochemical studies showed that Ex-4 pretreatment significantly alleviated blood–brain barrier leakage. Finally, Ex-4 pretreatment stimulated hippocampal expression of phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), a known target of GLP-1/GLP-1R signaling. These findings indicate that Ex-4 pretreatment may protect against KA-induced neuronal damage by regulating GLP-1R/CREB-mediated signaling pathways.

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Section: Discussionsupporting

confidence: 92%

Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death

Ahn

Shin

Jeong

et al. 2021

Cells

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“…Moreover, an increase in AQP4 in the placenta and fetal membrane from the patient in our study, may be indirect evidence of the increase of AQP4 in the circulation and the brain (27,59). Previous study has found a significant increase in the AQP4 protein in the whole brain during pregnancy in Sprague-Dawley rats (59)(60)(61), suggesting that the increase may be an adaptive adjustment during gestation. However, it has been revealed in rodent experiments that the upregulation of AQP4 in the brain increases the susceptibility of tissues to an autoimmune demyelinating disease attack during and after pregnancy (62).…”

Section: Relationship Between Pregnancy-related Dynamic Immune Changes and Acute Disseminated Encephalomyelitis Pathogenesissupporting

confidence: 60%

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

Deng

Qiu

et al. 2021

Front. Immunol.

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The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion. The expression of HMGB1, TLR4, Nf-κB, AQP4, IL-2, IL-4, IL-6, and TNF-α in the fetal membrane and placenta was compared between the patient with pregnancy-related ADEM and a woman with a normal pregnancy using Real-time qPCR and western blotting (WB). The patient was diagnosed with ADEM in the early stage of pregnancy after showing limb weakness symptoms. In the third month of gestation, the symptoms worsened, with a disturbance of consciousness and breathing. After the abortion, the patient relapsed with vertigo and visual rotation. Analysis of lymphocyte subsets by flow cytometry showed that B lymphocytes increased, while natural killer T lymphocytes decreased. WB and Real-time qPCR showed that the expression levels of HMGB1, TLR4, Nf-κB, AQP4, and IL-6 in the fetal membrane and placenta were higher in the patient with pregnancy-related ADEM than in the woman with a normal pregnancy, while those of IL-2 were lower in the patient than in the woman with a normal pregnancy. The local immune changes and the activation of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface may be related to the pathogenesis of ADEM.

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“…29 Previous studies demonstrated in preeclamptic placenta an increment of AQP9 expression by Western blot or immunostaining. 15,20,22,26,29 To the best of our knowledge, this is the first study to the current time that has assessed circulating levels of AQP9 in patients with early-onset preeclampsia and compared them with normotensive pregnant women. Also, we included the control and early-onset preeclampsia patient groups that were matched for maternal age, gestational age at blood sample collection, and BMI.…”

Section: Discussionmentioning

confidence: 97%

“…Also, these results might present some evidence towards the brain edema after eclampsia-like seizure and help in the research for treatments for gestational hypertensive disorders. 29 Previous studies demonstrated in preeclamptic placenta an increment of AQP9 expression by Western blot or immunostaining. 15,20,22,26,29 To the best of our knowledge, this is the first study to the current time that has assessed circulating levels of AQP9 in patients with early-onset preeclampsia and compared them with normotensive pregnant women.…”

Section: Discussionmentioning

confidence: 97%

Increased maternal serum aquaporin‐9 expression in pregnancies complicated with early‐onset preeclampsia

Ölmez

Oğlak

Özköse

2021

J of Obstet and Gynaecol

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Objectives We aimed to evaluate maternal serum aquaporin‐9 (AQP9) concentrations in patients with early‐onset preeclampsia and compare them with the uncomplicated control group with normal blood pressure. Methods This was a prospective case–control study including pregnant women who were diagnosed with early‐onset preeclampsia between 200/7–340/7 weeks of gestation. Demographic and clinical characteristics, complete blood count and biochemical parameters, and serum AQP9 concentrations were documented. A receiver operating characteristic (ROC) curve was constructed to illustrate the sensitivity and specificity performance characteristics of AQP9 and a cut‐off value was estimated by using the Youden index. Results The mean serum concentrations of maternal AQP9 were significantly increased in the early‐onset preeclampsia group (722.22 ± 211.80 pg/mL) than the control group (499.97 ± 68.89 pg/mL, p < 0.001). When we analyze the area under the ROC curve (AUC), the serum AQP9 value can be considered a statistically significant parameter for diagnosing preeclampsia. According to the Youden index, a 587.70 ng/mL cut‐off value of serum AQP9 level can be used to diagnose early‐onset preeclampsia with 80.0% sensitivity and 89.7% specificity. Conclusion Maternal serum AQP9 concentrations were significantly increased in early‐onset preeclampsia patients than healthy normotensive pregnant patients. We suggest that AQP9 might be a crucial biomarker of the inflammatory process in early‐onset preeclampsia.

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Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

Cited by 15 publications

References 41 publications

Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death

Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

Increased maternal serum aquaporin‐9 expression in pregnancies complicated with early‐onset preeclampsia

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