Brain inflammation may play an important role in the pathophysiology of early
brain injury after
subarachnoid hemorrhage (SAH). Our aim was to demonstrate
brain inflammation development and to determine whether
isoflurane, a clinically available volatile
anesthetic agent, prevents
brain inflammation after SAH. This study used 162 8-week-old male CD-1 mice. We induced SAH with endovascular perforation in mice and randomly assigned animals to
sham-operated (n=21), SAH+vehicle-air (n=35) and SAH+2%
isoflurane (n=31). In addition to the evaluation of
brain injury (neurological scores,
brain edema and
Evans blue dye extravasation),
brain inflammation was evaluated by means of expression changes in markers of inflammatory cells (ionized
calcium binding adaptor molecule-1,
myeloperoxidase),
cytokines (
tumor necrosis factor [TNF]-α,
interleukin-1β),
adhesion molecules (intercellular adhesion molecule [ICAM]-1,
P-selectin), inducers of
inflammation (
cyclooxygenase-2, phosphorylated
c-Jun N-terminal kinase [p-JNK]) and endothelial cell activation (
von Willebrand factor) at 24h post-SAH.
Sphingosine kinase inhibitor (
N, N-dimethylsphingosine [DMS]) and
sphingosine-1-phosphate receptor-1/3 antagonist (
VPC23019) were used to block
isoflurane's effects (n=22, each). SAH caused early
brain injury, which was associated with
inflammation so that all evaluated markers of
inflammation were increased.
Isoflurane significantly inhibited both
brain injury (P<0.001, respectively) and
inflammation (
myeloperoxidase, P=0.022;
interleukin-1β, P=0.002; TNF-α, P=0.015;
P-selectin, P=0.010; ICAM-1, P=0.016; p-JNK, P<0.001;
cyclooxygenase-2, P=0.003, respectively). This beneficial effect of
isoflurane was abolished with DMS and
VPC23019.
Isoflurane may suppress post-SAH
brain inflammation possibly via the
sphingosine-related pathway.