S100B modulates IL-6 release and cytotoxicity from hypothermic brain cells and inhibits hypothermia-induced axonal outgrowth.
Brain protection is essential during neonatal and pediatric cardiac surgery. Deep hypothermia is still the most important method for achieving neuroprotection during cardiopulmonary bypass. Previously, we could demonstrate that deep hypothermia induces substantial cytotoxicity in brain cells as well as increased release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays an important role in neuroprotection and neuroregeneration. Deep hypothermia is also associated with increased levels of the astrocytic protein S100B in the serum and cerebrospinal fluid of patients. Since S100B may modulate pro-inflammatory cytokines and may stimulate neurite outgrowth, we have tested the hypothesis that nanomolar concentrations of S100B may increase IL-6 release from brain cells and support axonal outgrowth from organotypic brain slices under hypothermic conditions. S100B administration substantially reduced neuronal and glial cytotoxicity under hypothermic conditions. In the presence of S100B hypothermia-induced IL-6 release in primary astrocytes was significantly increased but reduced in BV-2 microglial cells and primary neurons. Surprisingly, deep hypothermia increased axonal outgrowth from brain slices and--in contrast to our hypothesis--this hypothermia-induced neurite outgrowth was inhibited by S100B. These data suggest that S100B differentially influences cytokine release and cytotoxicity from distinct brain cells and may inhibit neuroregeneration by suppressing hypothermia-induced axonal outgrowth.
Schmitt
Katharina R L
KR
Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. kschmitt@dhzb.de
Kern
Claudia
C
Lange
Peter E
PE
Berger
Felix
F
Abdul-Khaliq
Hashim
H
Hendrix
Sven
S
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects; D001369:Axons / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D007035:Hypothermia; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013696:Temperature; D013997:Time Factors
D015850:Interleukin-6; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse