title: Methylprednisolone attenuates hypothermia- and rewarming-induced cytotoxicity and IL-6 release in isolated primary astrocytes, neurons and BV-2 microglia cells.
abstract: Brain protection is crucial during neonatal and pediatric cardiac surgery. The major methods for brain protection are the administration of steroids and deep hypothermia. Therefore, we have investigated the impact of methylprednisolone (MP) administration and deep hypothermia on neonatal mouse astrocytes, neurons and BV-2 microglia cells. Brain cells were pretreated with MP (100 mM) and incubated according to a deep hypothermia protocol mimicking temperature changes during cardiac surgery in children: deep hypothermia (2 h at 17 degrees C, phase 1), slow rewarming (2 h up to 37 degrees C, phase 2), and normothermia (20 h at 37 degrees C, phase 3). In all brain-related cell types cytotoxicity was investigated as well as the release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays a major role in neuroprotection and neuroregeneration. Deep hypothermia induces substantial cytotoxicity and the secretion of IL-6 by astrocytes, BV-2 microglia cells and neurons. MP administration has no influence on the cell survival and IL-6 release of normothermic astrocytes, BV-2 microglia cells and neurons, while hypothermia-induced cytotoxicity and IL-6 secretion are significantly suppressed by MP. These data suggest that MP increases cell survival after deep hypothermia but also suppresses important neuroprotective and regenerative processes induced by IL-6. Hence, more specific immune modulation than that provided by MP may be needed to protect the brain during neonatal and pediatric cardiac surgery.
authors.affiliation: Department for Congenital Heart Disease and Pediatric Cardiology, German Heart Institute Berlin, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. kschmitt@dhzb.de
authors.forename: Katharina R L
authors.initials: KR
authors.lastname: Schmitt
authors.forename: Claudia
authors.initials: C
authors.lastname: Kern
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.forename: Oliver
authors.initials: O
authors.lastname: Ullrich
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
authors.forename: Hashim
authors.initials: H
authors.lastname: Abdul-Khaliq
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000166:cytology; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008775:Methylprednisolone / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology*; D017694:Rewarming / Q000009:adverse effects*
chemical_list: D007155:Immunologic Factors; D015850:Interleukin-6; D018696:Neuroprotective Agents; D008775:Methylprednisolone