دورية أكاديمية
Endothelial cell disruption drives increased blood-brain barrier permeability and cerebral edema in the Dahl SS/jr rat model of superimposed preeclampsia.
| العنوان: | Endothelial cell disruption drives increased blood-brain barrier permeability and cerebral edema in the Dahl SS/jr rat model of superimposed preeclampsia. |
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| المؤلفون: | Maeda KJ; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi., McClung DM; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.; Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi., Showmaker KC; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.; Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi., Warrington JP; Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi., Ryan MJ; Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi., Garrett MR; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.; Department of Medicine (Nephrology), University of Mississippi Medical Center, Jackson, Mississippi., Sasser JM; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi. |
| المصدر: | American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2021 Feb 01; Vol. 320 (2), pp. H535-H548. Date of Electronic Publication: 2020 Dec 04. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Capillary Permeability*, Blood-Brain Barrier/*metabolism , Brain Edema/*pathology , Endothelial Cells/*ultrastructure , Pre-Eclampsia/*pathology, Animals ; Basement Membrane/ultrastructure ; Blood-Brain Barrier/ultrastructure ; Brain Edema/metabolism ; Cytoplasmic Vesicles/ultrastructure ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/ultrastructure ; Female ; Pre-Eclampsia/metabolism ; Pregnancy ; Rats ; Rats, Inbred Dahl ; Rats, Sprague-Dawley ; Tight Junctions/ultrastructure |
| مستخلص: | Preeclampsia is characterized by increases in blood pressure and proteinuria in late pregnancy, and neurological symptoms can appear in the form of headaches, blurred vision, cerebral edema, and, in the most severe cases, seizures (eclampsia). The causes for these cerebral manifestations remain unknown, so the use of animal models that mimic preeclampsia is essential to understanding its pathogenesis. The Dahl salt-sensitive (Dahl SS/jr) rat model develops spontaneous preeclampsia superimposed on chronic hypertension; therefore, we hypothesized that the Dahl SS/jr rat would display cerebrovascular features similar to those seen in human preeclampsia. Furthermore, we predicted that this model would allow for the identification of mechanisms underlying these changes. The pregnant Dahl SS/jr rat displayed increased cerebral edema and blood-brain barrier disruption despite tighter control of cerebral blood flow autoregulation and vascular smooth muscle myogenic tone. Analysis of cerebral endothelial cell morphology revealed increased opening of tight junctions, basement membrane dissolution, and vesicle formation. RNAseq analysis identified that genes related to endothelial cell tight junctions and blood-brain barrier integrity were differentially expressed in cerebral vessels from pregnant Dahl SS/jr compared with healthy pregnant Sprague Dawley rats. Overall, our data reveal new insights into mechanisms involved in the cerebrovascular dysfunction of preeclampsia. NEW & NOTEWORTHY This study uses the Dahl SS/jr rat as a preclinical model of spontaneous superimposed preeclampsia to demonstrate uncoupling of cerebral vascular permeability and blood-brain barrier disruption from cerebral blood flow autoregulatory dysfunction and myogenic tone. Additionally, the data presented in this study lay the foundational framework on which future experiments assessing specific transcellular transport components such as individual transporter protein expression and components of the vesicular transport system (caveolae) can be built to help reveal a potential direct mechanistic insight into the causes of cerebrovascular complications during preeclamptic pregnancies. |
| References: | J Obstet Gynaecol Res. 2015 Apr;41(4):540-50. (PMID: 25370989) J Cereb Blood Flow Metab. 2013 Apr;33(4):465-78. (PMID: 23321787) J Hypertens. 2017 Dec;35(12):2479-2485. (PMID: 28800041) Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H541-50. (PMID: 18055511) Semin Perinatol. 2009 Jun;33(3):130-7. (PMID: 19464502) Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308) J Transl Med. 2011 Jun 26;9:98. (PMID: 21703019) Neurology. 1998 Nov;51(5):1369-76. (PMID: 9818862) Sci Rep. 2017 Jul 19;7(1):5887. (PMID: 28725005) Hypertension. 2007 Feb;49(2):334-40. (PMID: 17200432) Minerva Ginecol. 2012 Aug;64(4):309-20. (PMID: 22728575) Transl Stroke Res. 2011 Dec;2(4):492-516. (PMID: 22299022) Am J Obstet Gynecol. 2013 Jun;208(6):468.e1-6. (PMID: 23395926) CNS Neurosci Ther. 2017 Dec;23(12):947-960. (PMID: 28961379) Integr Blood Press Control. 2015 Mar 03;8:7-12. (PMID: 25767405) Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677) Neurobiol Dis. 2017 Nov;107:41-56. (PMID: 27425887) J Pharm Sci Exp Pharmacol. 2017;2017(1):21-27. (PMID: 29333537) Hypertension. 2001 Sep;38(3 Pt 2):718-22. (PMID: 11566964) J Drug Target. 2006 May;14(4):191-214. (PMID: 16777679) Nucleic Acids Res. 2012 May;40(10):4288-97. (PMID: 22287627) J Endocrinol. 2017 Jan;232(1):R27-R44. (PMID: 27729465) Stroke. 2003 Jun;34(6):1484-90. (PMID: 12750541) Am J Physiol Regul Integr Comp Physiol. 2015 Jul 1;309(1):R62-70. (PMID: 25904684) Physiology (Bethesda). 2015 Mar;30(2):139-47. (PMID: 25729059) Cardiovasc J Afr. 2016 Mar-Apr;27(2):89-94. (PMID: 27213856) Curr Hypertens Rep. 2019 May 23;21(7):52. (PMID: 31123841) Sci Rep. 2020 Jan 16;10(1):467. (PMID: 31949182) Hypertension. 2011 Dec;58(6):1126-31. (PMID: 22068864) Hypertension. 2012 Sep;60(3):705-11. (PMID: 22824983) BMJ. 2014 Apr 15;348:g2301. (PMID: 24735917) Am J Physiol Regul Integr Comp Physiol. 2015 Dec 1;309(11):R1425-31. (PMID: 26400187) Early Hum Dev. 2016 Nov;102:47-50. (PMID: 27659865) Biomolecules. 2020 Feb 14;10(2):. (PMID: 32075042) Curr Hypertens Rep. 2016 Sep;18(9):68. (PMID: 27590522) J Clin Invest. 2008 Jan;118(1):29-39. (PMID: 18097473) FASEB J. 2012 Jan;26(1):355-62. (PMID: 21911594) Reprod Sci. 2013 Sep;20(9):1046-54. (PMID: 23420820) Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886) Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H1071-6. (PMID: 17056666) Semin Reprod Endocrinol. 1998;16(1):5-15. (PMID: 9654603) Eur J Epidemiol. 2013 Jan;28(1):1-19. (PMID: 23397514) J Appl Physiol (1985). 2011 Feb;110(2):329-39. (PMID: 21071591) Clin Exp Obstet Gynecol. 2008;35(3):194-7. (PMID: 18754291) Nat Rev Nephrol. 2014 Aug;10(8):466-80. (PMID: 25003615) Physiol Rep. 2014 Aug 28;2(8):. (PMID: 25168877) Bioinformatics. 2005 Aug 15;21(16):3439-40. (PMID: 16082012) |
| معلومات مُعتمدة: | P20 GM103476 United States GM NIGMS NIH HHS; R01 HL136684 United States HL NHLBI NIH HHS; T32 HL105324 United States HL NHLBI NIH HHS; P20 GM104357 United States GM NIGMS NIH HHS; R01HL134711 HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI); R01 HL134711 United States HL NHLBI NIH HHS; R01 HL137673 United States HL NHLBI NIH HHS; R01HL136684 HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI); T32HL105324 HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI); P20 GM121334 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: autoregulation; cerebral blood flow; electron microscopy; fluorescent dextran; myogenic tone |
| تواريخ الأحداث: | Date Created: 20201204 Date Completed: 20210218 Latest Revision: 20220202 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8082793 |
| DOI: | 10.1152/ajpheart.00383.2020 |
| PMID: | 33275518 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1539 |
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| DOI: | 10.1152/ajpheart.00383.2020 |