I am hoping to start using this model, but need more details about LPS administration.
For a 1-hour infusion, I would suggest to do a slight anesthesia (eg. isoflurane), because rats won't just tolerate the iv- line. Single injections are usually tolerated awake. Perhaps the publication of Podjarny Semin Nephrol. 2004 Nov; 24(6): 596–606 can be useful for your purposes to set up your model.
Thank you so much Tanja. Yes, I reviewed the Podjarny paper, and it gives a nice overview of the different models of pre-E. We like the LPS-based model the best, for our purposes. However, it seems that there's quite a bit of variation in timing of LPS administration, and routes of administration as well. I like the idea of dosing the LPS earlier in gestation, because it gives more time for the inflammation response and placental maldevelopment to occur before we trial a therapeutic intervention later in gestation. Do you know why someone would not just dose the LPS as a single injection awake, instead of a 1 hr infusion? Are single injections poorly tolerated, in that they increase morbidity and mortality? Thanks so much for your input here as we start to design a model that is well-tolerated, but also effective.
It depends on LPS- dosing, timing and even genetical background of your animals. Perhaps you know the publication of Shannon Copeland 10.1128/CDLI.12.1.60-67.2005. Depending on whether you want to mimic acute septical conditions (risk for high mortality and/or morbidity) or rather a chronic inflammatory state you will choose your appropriate model. For preeclampsia you probably "just" aim at a sympathetic hyperstimulation in your pregnant animals and would like to avoid neuroinflammation and acute vascular leakage etc. as a side effect of LPS justifying lower levels of LPS and a slow perfusion rate.
Xue et al (PLOS one 2015) https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0124001&type=printable
administered low single doses of LPS 0.5 μg/kg to pregnant rats on GD 5, perhaps this could be a suitable approach for you.
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