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Fingolimod against endotoxin‐induced fetal brain injury in a rat model
Author(s) -
Yavuz And,
Sezik Mekin,
Ozmen Ozlem,
Asci Halil
Publication year - 2017
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.13444
Subject(s) - fingolimod , medicine , neuroprotection , saline , fetus , pharmacology , sphingosine 1 phosphate , inflammation , multiple sclerosis , anesthesia , sphingosine , endocrinology , immunology , receptor , pregnancy , biology , genetics
Aim Fingolimod is a sphingosine‐1‐phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Methods Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)‐6, caspase‐3, and S100β on immunohistochemistry. Results Maternal fingolimod treatment attenuated endotoxin‐related fetal brain injury and led to lower immunoreactions for IL‐6, caspase‐3, and S100β compared with endotoxin controls ( P < 0.0001 for all comparisons). Conclusion Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth‐related fetal brain injury with inhibitory effects on inflammation and apoptosis.