The Contribution of Normal Pregnancy to Eclampsia
Eclampsia, clinically defined as unexplained seizure in a woman with preeclampsia, is a life threatening complication unique to the pregnant state. However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting...
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| description | Eclampsia, clinically defined as unexplained seizure in a woman with preeclampsia, is a life threatening complication unique to the pregnant state. However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting pregnancy alone may predispose the brain to seizure. Here, we hypothesized that normal pregnancy lowers seizure threshold and investigated mechanisms by which pregnancy may affect seizure susceptibility, including neuroinflammation and plasticity of gamma-aminobutyric acid type A receptor (GABAAR) subunit expression. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n = 6). Seizure-induced vasogenic edema was also measured. Further, activation of microglia, a measure of neuroinflammation (n = 6-8/group), and GABAAR δ- and γ2-subunit protein expression in the cerebral cortex and hippocampus (n = 6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg rats (36.7±9.6 vs. 65.0±14.5 mg/kg PTZ; p |
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However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting pregnancy alone may predispose the brain to seizure. Here, we hypothesized that normal pregnancy lowers seizure threshold and investigated mechanisms by which pregnancy may affect seizure susceptibility, including neuroinflammation and plasticity of gamma-aminobutyric acid type A receptor (GABAAR) subunit expression. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n = 6). Seizure-induced vasogenic edema was also measured. Further, activation of microglia, a measure of neuroinflammation (n = 6-8/group), and GABAAR δ- and γ2-subunit protein expression in the cerebral cortex and hippocampus (n = 6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg rats (36.7±9.6 vs. 65.0±14.5 mg/kg PTZ; p<0.01) that was associated with greater vasogenic edema formation (78.55±0.11 vs. 78.04±0.19% water; p<0.05). The % of active microglia was similar between groups; however, pregnancy was associated with downregulation of cortical GABAAR-δ and hippocampal GABAAR-γ2 expression. Overall, pregnancy appears to be a state of increased seizure susceptibility that is not due to neuroinflammation, but rather is associated with reduced expression of GABAAR subunits and greater edema. Understanding neurophysiological changes occurring in normal pregnancy could allow for better prevention and management of de novo seizure, including pathologic states such as eclampsia.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0133953</identifier><identifier>PMID: 26218425</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Binding sites ; Blood-brain barrier ; Brain ; Cerebral cortex ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Cerebral Cortex - physiopathology ; Eclampsia ; Eclampsia - metabolism ; Eclampsia - pathology ; Eclampsia - physiopathology ; Edema ; Female ; Gene expression ; Gene Expression Regulation ; Hippocampus ; Hippocampus - metabolism ; Hippocampus - pathology ; Hippocampus - physiopathology ; Hypertension ; Inflammation ; Medicine ; Microglia ; Neurosciences ; Pentylenetetrazole ; Pre-eclampsia ; Preeclampsia ; Pregnancy ; Pregnant women ; Rats ; Receptors, GABA-A - metabolism ; Rodents ; Seizing ; Seizures (Medicine) ; Seizures - metabolism ; Seizures - pathology ; Seizures - physiopathology ; γ-Aminobutyric acid A receptors</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0133953-e0133953</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Johnson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Johnson et al 2015 Johnson et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-373479aed7b5ef08b9ce9c436f198da022ba570e4b3d22b367953f0df057fcca3</citedby><cites>FETCH-LOGICAL-c692t-373479aed7b5ef08b9ce9c436f198da022ba570e4b3d22b367953f0df057fcca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517916/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517916/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26218425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Abbie Chapman</creatorcontrib><creatorcontrib>Nagle, Keith J</creatorcontrib><creatorcontrib>Tremble, Sarah M</creatorcontrib><creatorcontrib>Cipolla, Marilyn J</creatorcontrib><title>The Contribution of Normal Pregnancy to Eclampsia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Eclampsia, clinically defined as unexplained seizure in a woman with preeclampsia, is a life threatening complication unique to the pregnant state. However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting pregnancy alone may predispose the brain to seizure. Here, we hypothesized that normal pregnancy lowers seizure threshold and investigated mechanisms by which pregnancy may affect seizure susceptibility, including neuroinflammation and plasticity of gamma-aminobutyric acid type A receptor (GABAAR) subunit expression. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n = 6). Seizure-induced vasogenic edema was also measured. Further, activation of microglia, a measure of neuroinflammation (n = 6-8/group), and GABAAR δ- and γ2-subunit protein expression in the cerebral cortex and hippocampus (n = 6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg rats (36.7±9.6 vs. 65.0±14.5 mg/kg PTZ; p<0.01) that was associated with greater vasogenic edema formation (78.55±0.11 vs. 78.04±0.19% water; p<0.05). The % of active microglia was similar between groups; however, pregnancy was associated with downregulation of cortical GABAAR-δ and hippocampal GABAAR-γ2 expression. Overall, pregnancy appears to be a state of increased seizure susceptibility that is not due to neuroinflammation, but rather is associated with reduced expression of GABAAR subunits and greater edema. Understanding neurophysiological changes occurring in normal pregnancy could allow for better prevention and management of de novo seizure, including pathologic states such as eclampsia.</description><subject>Animals</subject><subject>Binding sites</subject><subject>Blood-brain barrier</subject><subject>Brain</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebral Cortex - physiopathology</subject><subject>Eclampsia</subject><subject>Eclampsia - metabolism</subject><subject>Eclampsia - pathology</subject><subject>Eclampsia - physiopathology</subject><subject>Edema</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Hippocampus - physiopathology</subject><subject>Hypertension</subject><subject>Inflammation</subject><subject>Medicine</subject><subject>Microglia</subject><subject>Neurosciences</subject><subject>Pentylenetetrazole</subject><subject>Pre-eclampsia</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Rats</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Rodents</subject><subject>Seizing</subject><subject>Seizures (Medicine)</subject><subject>Seizures - metabolism</subject><subject>Seizures - pathology</subject><subject>Seizures - physiopathology</subject><subject>γ-Aminobutyric acid A receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkk1v1DAQhiMEoh_wDxBEQkJw2MWOY3t9QapWBVaqKILC1XKccdYrJ97aCWr_Pd5uWm1QD8gHW-Nn3vGM3yx7hdEcE44_bvwQOuXmW9_BHGFCBCVPsmMsSDFjBSJPD85H2UmMG4QoWTD2PDsqWIEXZUGPM3y1hnzpuz7Yauit73Jv8m8-tMrl3wM0ner0bd77_Fw71W6jVS-yZ0a5CC_H_TT79fn8avl1dnH5ZbU8u5hpJop-RjgpuVBQ84qCQYtKaBC6JMxgsagVKopKUY6grEidzoTx9H6DaoMoN1orcpq92etunY9y7DZKzISguEQYJWK1J2qvNnIbbKvCrfTKyruAD41UobfagQTKBOCaaVzTEiFIRVGtOEOVSePhJGl9GqsNVQu1hjQR5Sai05vOrmXj_8iSYi4wSwLvR4HgrweIvWxt1OCc6sAP6d0cIUISKxL69h_08e5GqlGpAdsZn-rqnag8KwtSMlzQHTV_hEqrhtbqZA1jU3yS8GGSkJgebvpGDTHK1c8f_89e_p6y7w7YNSjXr6N3d56KU7Dcgzr4GAOYhyFjJHfOvp-G3Dlbjs5Oaa8PP-gh6d7K5C8HZfEM</recordid><startdate>20150728</startdate><enddate>20150728</enddate><creator>Johnson, Abbie Chapman</creator><creator>Nagle, Keith J</creator><creator>Tremble, Sarah M</creator><creator>Cipolla, Marilyn J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150728</creationdate><title>The Contribution of Normal Pregnancy to Eclampsia</title><author>Johnson, Abbie Chapman ; Nagle, Keith J ; Tremble, Sarah M ; Cipolla, Marilyn J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-373479aed7b5ef08b9ce9c436f198da022ba570e4b3d22b367953f0df057fcca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Binding sites</topic><topic>Blood-brain barrier</topic><topic>Brain</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnson, Abbie Chapman</au><au>Nagle, Keith J</au><au>Tremble, Sarah M</au><au>Cipolla, Marilyn J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Contribution of Normal Pregnancy to Eclampsia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-28</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0133953</spage><epage>e0133953</epage><pages>e0133953-e0133953</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Eclampsia, clinically defined as unexplained seizure in a woman with preeclampsia, is a life threatening complication unique to the pregnant state. However, a subpopulation of women with seemingly uncomplicated pregnancies experience de novo seizure without preeclamptic signs or symptoms, suggesting pregnancy alone may predispose the brain to seizure. Here, we hypothesized that normal pregnancy lowers seizure threshold and investigated mechanisms by which pregnancy may affect seizure susceptibility, including neuroinflammation and plasticity of gamma-aminobutyric acid type A receptor (GABAAR) subunit expression. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n = 6). Seizure-induced vasogenic edema was also measured. Further, activation of microglia, a measure of neuroinflammation (n = 6-8/group), and GABAAR δ- and γ2-subunit protein expression in the cerebral cortex and hippocampus (n = 6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg rats (36.7±9.6 vs. 65.0±14.5 mg/kg PTZ; p<0.01) that was associated with greater vasogenic edema formation (78.55±0.11 vs. 78.04±0.19% water; p<0.05). The % of active microglia was similar between groups; however, pregnancy was associated with downregulation of cortical GABAAR-δ and hippocampal GABAAR-γ2 expression. Overall, pregnancy appears to be a state of increased seizure susceptibility that is not due to neuroinflammation, but rather is associated with reduced expression of GABAAR subunits and greater edema. Understanding neurophysiological changes occurring in normal pregnancy could allow for better prevention and management of de novo seizure, including pathologic states such as eclampsia.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26218425</pmid><doi>10.1371/journal.pone.0133953</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Binding sites Blood-brain barrier Brain Cerebral cortex Cerebral Cortex - metabolism Cerebral Cortex - pathology Cerebral Cortex - physiopathology Eclampsia Eclampsia - metabolism Eclampsia - pathology Eclampsia - physiopathology Edema Female Gene expression Gene Expression Regulation Hippocampus Hippocampus - metabolism Hippocampus - pathology Hippocampus - physiopathology Hypertension Inflammation Medicine Microglia Neurosciences Pentylenetetrazole Pre-eclampsia Preeclampsia Pregnancy Pregnant women Rats Receptors, GABA-A - metabolism Rodents Seizing Seizures (Medicine) Seizures - metabolism Seizures - pathology Seizures - physiopathology γ-Aminobutyric acid A receptors |
| title | The Contribution of Normal Pregnancy to Eclampsia |
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