title: Therapeutic hypothermia modulates complement factor C3a and C5a levels in a rat model of hypoxic ischemic encephalopathy.
abstract: BACKGROUND
  Therapeutic hypothermia (HT) is the only intervention that improves outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). However, the multifactorial mechanisms by which HT impacts HIE are incompletely understood. The complement system plays a major role in the pathogenesis of ischemia-reperfusion injuries such as HIE. We have previously demonstrated that HT modulates complement activity in vitro.
  
  
  METHODS
  Term equivalent rat pups were subjected to unilateral carotid ligation followed by hypoxia (8% O2) for 45 min to simulate HIE. A subset of animals was subjected to HT (31-32°C for 6 h). Plasma and brain levels of C3a and C5a were measured. Receptors for C3a (C3aR) and C5a (C5aR) along with C1q, C3, and C9 were characterized in neurons, astrocytes, and microglia.
  
  
  RESULTS
  We found that HT increased systemic expression of C3a and decreased expression of C5a after HIE. In the brain, C3aR and C5aR are predominantly expressed on microglia after HIE. HT increased local expression of C3aR and decreased expression on C5aR after HIE. Furthermore, HT decreased local expression of C1q, C3-products, and C9 in the brain.
  
  
  CONCLUSIONS
  HT is associated with significant alteration of complement effectors and their cognate receptors. Complement modulation may improve outcomes in neonatal HIE.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.|Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia.|Children's Specialty Group, Norfolk, Virginia.|Division of Neonatology, Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: Tushar A
authors.initials: TA
authors.lastname: Shah
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Jasmine E
authors.initials: JE
authors.lastname: Nejad
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Haree K
authors.initials: HK
authors.lastname: Pallera
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Lattanzio
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Rawad
authors.initials: R
authors.lastname: Farhat
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Parvathi S
authors.initials: PS
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hair
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.|Children's Specialty Group, Norfolk, Virginia.|Division of Neonatology, Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: W Thomas
authors.initials: WT
authors.lastname: Bass
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.|Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Neel K
authors.initials: NK
authors.lastname: Krishna
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000097:blood* / Q000628:therapy; D015926:Complement C3a / Q000032:analysis*; D015936:Complement C5a / Q000032:analysis*; D007036:Hypothermia, Induced; D000860:Hypoxia; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000628:therapy; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013696:Temperature; D013997:Time Factors
chemical_list: D015926:Complement C3a; D015936:Complement C5a