PMID- 19368819
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20091030
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1264
DP  - 2009 Apr 6
TI  - Administration of Human Protein-C concentrate prevents apoptotic brain cell death 
      after experimental sepsis.
PG  - 119-26
LID - 10.1016/j.brainres.2009.01.053 [doi]
AB  - Activated Protein C renders anti-apoptotic properties in neurons and endothelial 
      cells. The aim of the present study was to evaluate the in vivo cytoprotective 
      role of Protein C zymogen (PC) administration in septic rat brain. Male Wistar 
      rats (n=60) were subjected to sepsis via Cecal Ligation and Puncture (CLP). 
      Animals were randomly divided either to receive 100 IU/kg human PC concentrate at 
      1, 7 and 13 h post CLP (CLP+PC group) or placebo treatment (CLP group). At 
      pre-specified time points (6, 12, 24, 36, 48 and 60 h post CLP) five animals from 
      either group were euthanized and the brain tissue was removed. Apoptosis in both 
      neurons (Neu-N+) and astroglia (GFAP+) was assessed by flow cytometry using 
      7-aminoactinomycin D (7AAD). Immunohistochemical detection of cleaved caspase 3, 
      bax, bcl-2, cytochrome c and caspase 8 was also performed. PC treated animals had 
      significantly reduced apoptosis in neurons at 6 and 24 h post CLP (p=0.04 and 
      p=0.016 respectively) and necrosis at 6, 12 and 60 h post CLP (p=0.008, p=0.012 
      and p=0.032 respectively). Astrocyte necrosis was also decreased in septic rats 
      receiving PC (6, 12 and 60 h post CLP p=0.008, p=0.016 and p=0.008 respectively). 
      In addition, active caspase 3, bax, cytochrome c and caspase 8 expression was 
      significantly decreased during early sepsis (6-36 h) while bcl-2 expression was 
      increased (24 h p=0.001 and 60 h p=0.001) in the PC treated animals compared to 
      placebo. PC concentrate administration in experimental sepsis produced a time 
      dependent inhibition of apoptosis in rat neurons and astrocytes. The inhibition 
      of sepsis related apoptosis concerned both the mitochondrial and caspase 8 
      dependent pathways.
FAU - Memos, Nikolaos
AU  - Memos N
AD  - First Department of Propaedeutic Surgery, Athens University Medical School, 
      Hippocration General Hospital, Athens, Greece.
FAU - Betrosian, Alex
AU  - Betrosian A
FAU - Messaris, Evangelos
AU  - Messaris E
FAU - Boutsikou, Maria
AU  - Boutsikou M
FAU - Kataki, Agapi
AU  - Kataki A
FAU - Chatzigianni, Emmy
AU  - Chatzigianni E
FAU - Nikolopoulou, Marilena
AU  - Nikolopoulou M
FAU - Leandros, Emmanuel
AU  - Leandros E
FAU - Konstadoulakis, Manousos
AU  - Konstadoulakis M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090205
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Protein C)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Astrocytes/drug effects/metabolism/pathology
MH  - Brain/*drug effects/metabolism/pathology
MH  - Caspases/metabolism
MH  - Cytochromes c/metabolism
MH  - *Cytoprotection
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Male
MH  - Neurons/drug effects/metabolism/pathology
MH  - Protein C/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sepsis/metabolism/*pathology
MH  - Time Factors
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2009/04/17 09:00
MHDA- 2009/11/18 06:00
CRDT- 2009/04/17 09:00
PHST- 2008/11/12 00:00 [received]
PHST- 2009/01/23 00:00 [revised]
PHST- 2009/01/24 00:00 [accepted]
PHST- 2009/04/17 09:00 [entrez]
PHST- 2009/04/17 09:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
AID - S0006-8993(09)00216-9 [pii]
AID - 10.1016/j.brainres.2009.01.053 [doi]
PST - ppublish
SO  - Brain Res. 2009 Apr 6;1264:119-26. doi: 10.1016/j.brainres.2009.01.053. Epub 2009 
      Feb 5.