title: C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model.
abstract: The concept of 'salvageble penumbra' has prompted both scientists and physicians to explore various neuroprotective approaches that could be beneficial during stroke therapy. Unfortunately, most of them have proved ineffective in targeting multiple cellular death cascades incited within the ischemic penumbra. Hypothermia has been shown to be capable of addressing this problem to some extent. Although many studies have shown that hypothermia targets several cellular processes, its effects on innate immune receptor-mediated apoptotic death still remain unclear. Moreover, whether inhibiting the signaling of innate immune receptors like complement anaphylatoxin C5a receptor (CD88) plays a role in this hypothermic neuroprotection still need to be deciphered. Using various types of ischemic insults in different neuronal cells, we confirm that hypothermia does indeed attenuate apoptotic neuronal cell death in vitro and this effect can be further enhanced by pharmacologically blocking or knocking out CD88. Thus, our study raises a promising therapeutic possibility of adding CD88 antagonists along with hypothermia to improve stroke outcomes.
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Thundyil
authors.forename: Dale
authors.initials: D
authors.lastname: Pavlovski
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Mathias
authors.initials: M
authors.lastname: Gelderblom
authors.forename: Tim
authors.initials: T
authors.lastname: Magnus
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000628:therapy*; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007036:Hypothermia, Induced; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D044087:Receptor, Anaphylatoxin C5a