Περίληψη:
Objective. To investigate whether apoptosis is a possible mechanism of
brain dysfunction occurring in septic syndrome.
Design: Experimental prospective study.
Setting. Laboratory of Surgical Research at the University of Athens.
Subjects: Male pathogen-free Wistar rats.
Interventions. Rats (n = 112) were subjected to sepsis by cecal ligation
and puncture. Sham-operated animals (n = 40) underwent the same
procedure but without ligation or puncture. Septic animals were either
randomly divided (n = 62) in six groups and studied at 6,12, 24, 36, 48,
and 60 hrs after the operation or monitored (n = 50) for 48 hrs as a
survival study group. Sham-operated animals were killed at 6, 12, 24,
36, 48, and 60 hrs after the procedure. Brain and cecum were then
removed and postfixed in paraffin sections. Apoptosis was evaluated by
light microscopy in hematoxylin and eosin-stained specimens and by
transmission electron microscopy. In paraffin-embedded sections,
immunostaining for bax, bcl-2, cytochrome c, and caspase-8 was done.
Measurements and Main Results., In septic rats, increased apoptosis was
detected in neurons of the CA1 region of the hippocampus, in choroid
plexus, and in Purkinje cells of the cerebellum. Bax immunopositivity
was found decreased after the septic insult (p = .03). Bax
immunoreactivity was altered as the septic syndrome evolved; it was
up-regulated in the early stages (6-12 hrs) and progressively decreased
in the late phases (p = .001). Cytochrome c presented a similar regional
pattern of expression and was found to be the sole gene marker carrying
an independent prognostic role (p = .03). Both bcl-2 and caspase-8
expression remained at constant levels at all times evaluated.
Conclusions. There is evidence that more neurons undergo apoptosis
during sepsis than in normal brain tissue in certain sites where the
blood-brain barrier is compromised. In this phenomenon, mitochondrial
gene regulators such as bax and products such as cytochrome c seem to
play important regulating and prognostic roles, respectively.
Συγγραφείς:
Messaris, E
Memos, N
Chatzigianni, E
Konstadoulakis, MM and
Menenakos, E
Katsaragakis, S
Voumvourakis, C
Androulakis, G
