Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model
Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesize...
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| Veröffentlicht in: | Hypertension research 2020-04, Vol.43 (4), p.263-270 |
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| creator | Huang, Qian Hu, Bihui Han, Xinjia Yang, Jinying Di, Xiaodan Bao, Junjie Liu, Huishu |
| description | Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P |
| doi_str_mv | 10.1038/s41440-019-0387-3 |
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Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.</description><identifier>ISSN: 0916-9636</identifier><identifier>EISSN: 1348-4214</identifier><identifier>DOI: 10.1038/s41440-019-0387-3</identifier><identifier>PMID: 31932642</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Animals ; Blood pressure ; Blood Pressure - physiology ; Cyclosporine - therapeutic use ; Cytokines - blood ; Disease Models, Animal ; Eclampsia - blood ; Female ; Hypertension ; Immunosuppressive Agents - therapeutic use ; Inflammation ; Inflammation - blood ; Inflammation - drug therapy ; Preeclampsia ; Pregnancy ; Rats ; Seizures - blood ; Seizures - drug therapy ; Seizures - etiology</subject><ispartof>Hypertension research, 2020-04, Vol.43 (4), p.263-270</ispartof><rights>2020© The Japanese Society of Hypertension 2020</rights><rights>The Japanese Society of Hypertension 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-3c8251d47c582f7c2ac6e8fd95f77d02c419a2b6af41bd7a3f54af4a41f1c9183</citedby><cites>FETCH-LOGICAL-c381t-3c8251d47c582f7c2ac6e8fd95f77d02c419a2b6af41bd7a3f54af4a41f1c9183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31932642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Qian</creatorcontrib><creatorcontrib>Hu, Bihui</creatorcontrib><creatorcontrib>Han, Xinjia</creatorcontrib><creatorcontrib>Yang, Jinying</creatorcontrib><creatorcontrib>Di, Xiaodan</creatorcontrib><creatorcontrib>Bao, Junjie</creatorcontrib><creatorcontrib>Liu, Huishu</creatorcontrib><title>Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model</title><title>Hypertension research</title><addtitle>Hypertens Res</addtitle><description>Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.</description><subject>Animals</subject><subject>Blood pressure</subject><subject>Blood Pressure - physiology</subject><subject>Cyclosporine - therapeutic use</subject><subject>Cytokines - blood</subject><subject>Disease Models, Animal</subject><subject>Eclampsia - blood</subject><subject>Female</subject><subject>Hypertension</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Inflammation - drug therapy</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Rats</subject><subject>Seizures - blood</subject><subject>Seizures - drug therapy</subject><subject>Seizures - etiology</subject><issn>0916-9636</issn><issn>1348-4214</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFqGzEQhkVpqB23D9BLEPTSi1qNpF1Jx2DSpBDopTkLWSslcnZXjrR7cJ8-MnYTyCGnmYHv_xn4EPoK9AdQrn4WAUJQQkGTekrCP6AlcKGIYCA-oiXV0BLd8naBzkvZUspUo-ETWnDQnLWCLdHTeu_6VHYpxxFfYjv4PqZsJ1-wd70ddiVaXHz8N2ePp4ec5vsHnH03uzje47Ivkx-iw3EMFR7sFNNYD2zH1zjp46PHtRMPqfP9Z3QWbF_8l9NcobtfV3_XN-T2z_Xv9eUtcVzBRLhTrIFOSNcoFqRj1rVehU43QcqOMidAW7ZpbRCw6aTloRF1twICOA2Kr9D3Y-8up6fZl8kMsTjf93b0aS6Gca6oZqI5oN_eoNs057F-Z5iQrWwkheZdikuphQIpKwVHyuVUSvbB7HIcbN4boOZgzRytmWrNHKwZXjMXp-Z5M_juJfFfE38Gyi6TOw</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Huang, Qian</creator><creator>Hu, Bihui</creator><creator>Han, Xinjia</creator><creator>Yang, Jinying</creator><creator>Di, Xiaodan</creator><creator>Bao, Junjie</creator><creator>Liu, Huishu</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20200401</creationdate><title>Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model</title><author>Huang, Qian ; Hu, Bihui ; Han, Xinjia ; Yang, Jinying ; Di, Xiaodan ; Bao, Junjie ; Liu, Huishu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-3c8251d47c582f7c2ac6e8fd95f77d02c419a2b6af41bd7a3f54af4a41f1c9183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Blood pressure</topic><topic>Blood Pressure - physiology</topic><topic>Cyclosporine - therapeutic use</topic><topic>Cytokines - blood</topic><topic>Disease Models, Animal</topic><topic>Eclampsia - blood</topic><topic>Female</topic><topic>Hypertension</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Inflammation</topic><topic>Inflammation - blood</topic><topic>Inflammation - drug therapy</topic><topic>Preeclampsia</topic><topic>Pregnancy</topic><topic>Rats</topic><topic>Seizures - blood</topic><topic>Seizures - drug therapy</topic><topic>Seizures - etiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Qian</creatorcontrib><creatorcontrib>Hu, Bihui</creatorcontrib><creatorcontrib>Han, Xinjia</creatorcontrib><creatorcontrib>Yang, Jinying</creatorcontrib><creatorcontrib>Di, Xiaodan</creatorcontrib><creatorcontrib>Bao, Junjie</creatorcontrib><creatorcontrib>Liu, Huishu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Hypertension research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Qian</au><au>Hu, Bihui</au><au>Han, Xinjia</au><au>Yang, Jinying</au><au>Di, Xiaodan</au><au>Bao, Junjie</au><au>Liu, Huishu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model</atitle><jtitle>Hypertension research</jtitle><addtitle>Hypertens Res</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>43</volume><issue>4</issue><spage>263</spage><epage>270</epage><pages>263-270</pages><issn>0916-9636</issn><eissn>1348-4214</eissn><abstract>Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>31932642</pmid><doi>10.1038/s41440-019-0387-3</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Blood pressure Blood Pressure - physiology Cyclosporine - therapeutic use Cytokines - blood Disease Models, Animal Eclampsia - blood Female Hypertension Immunosuppressive Agents - therapeutic use Inflammation Inflammation - blood Inflammation - drug therapy Preeclampsia Pregnancy Rats Seizures - blood Seizures - drug therapy Seizures - etiology |
| title | Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model |
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