TY - JOUR
TI - Administration of Human Protein-C concentrate prevents apoptotic brain
cell death after experimental sepsis
AU - Memos, Nikolaos
AU - Betrosian, Alex
AU - Messaris, Evangelos and
AU - Boutsikou, Maria
AU - Kataki, Agapi
AU - Chatzigianni, Emmy and
AU - Nikolopoulou, Marilena
AU - Leandros, Emmanuel
AU - Konstadoulakis,
AU - Manousos
JO - Brain Research
PY - 2009
VL - 1264
TODO - null
SP - 119-126
PB - ELSEVIER SCIENCE BV
SN - 0006-8993
TODO - 10.1016/j.brainres.2009.01.053
TODO - Sepsis; Brain; Apoptosis; Protein C zymogen
TODO - 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. (C) 2009 Elsevier B.V. All rights reserved.
ER -