Document Detail


Pregnant serum induces neuroinflammation and seizure activity via TNFα.
MedLine Citation:
PMID:  22281105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective role of the BBB that prevents exposure of the brain to hyperexcitable factors.
Authors:
Marilyn J Cipolla; Aya D Pusic; Yelena Y Grinberg; Abbie C Chapman; Matthew E Poynter; Richard P Kraig
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-16
Journal Detail:
Title:  Experimental neurology     Volume:  234     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-14     Completed Date:  2012-05-04     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  398-404     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / drug effects,  metabolism
Evoked Potentials / physiology*
Female
Hippocampus / physiopathology*
Inflammation Mediators / metabolism
Microglia / physiology
Neurons / physiology*
Pregnancy
Rats
Rats, Wistar
Serum
Signal Transduction / physiology
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
ID/Acronym/Agency:
3-RO1 NS019108-23S1/NS/NINDS NIH HHS; 3R01 NS045940-05S1/NS/NINDS NIH HHS; 3R01 NS045940-06S1/NS/NINDS NIH HHS; P01 HD009402/HD/NICHD NIH HHS; P01 HD09402/HD/NICHD NIH HHS; P01 HL095488/HL/NHLBI NIH HHS; P01 HL095488/HL/NHLBI NIH HHS; P01 HL095488-02/HL/NHLBI NIH HHS; P01 HL095488-03/HL/NHLBI NIH HHS; P20RR15557/RR/NCRR NIH HHS; R01 HL089177/HL/NHLBI NIH HHS; R01 NS019108/NS/NINDS NIH HHS; R01 NS045940/NS/NINDS NIH HHS; R01 NS045940/NS/NINDS NIH HHS; R01 NS045940-05A2S1/NS/NINDS NIH HHS; R01 NS045940-06S1/NS/NINDS NIH HHS; R01 NS045940-07/NS/NINDS NIH HHS; R01 NS045940-08/NS/NINDS NIH HHS; R01 NS19108/NS/NINDS NIH HHS; T32-GM07839/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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