Cerebral ischemia leads to astrocyte's activation and
glial scar formation.
Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that
sevoflurane has
neuroprotective effects against
ischemic stroke, but its effects on
ischemia-induced formation of
astrogliosis and
glial scar are unknown. This study was designed to investigate the effect of
sevoflurane postconditioning on
astrogliosis and
glial scar formation in
ischemic stroke model both in vivo and in vitro. The results showed that 2.5% of
sevoflurane postconditioning could significantly reduce
infarction volume and improve
neurologic deficits. And it could also decrease the expression of the
glial scar marker
glial fibrillary acidic protein (GFAP),
neurocan and
phosphacan in the peri-
infarct region and markedly reduce the thickness of
glial scar after
ischemia/reperfusion (I/R). Consistent with the in vivo data, in the
oxygen and
glucose deprivation/reoxygenation (OGD/Re) model,
sevoflurane postconditioning could protect astrocyte against OGD/Re-induced injury, decrease the expression of GFAP,
neurocan and
phosphacan. Further studies demonstrated that
sevoflurane postconditioning could down-regulate the expression of Lamp1 and active
cathepsin B, and block I/R or OGD/Re-induced release of
cathepsin B from the lysosomes into cytoplasm. In order to confirm whether inhibition of
cathepsin B could attenuate the formation of
glial scar, we used
cathepsin B inhibitor
CA-074Me as a positive control. The results showed that inhibition of
cathepsin B could decrease the expression of GFAP,
neurocan and
phosphacan. Taken together,
sevoflurane postconditioning can attenuate
astrogliosis and
glial scar formation after
ischemic stroke, associating with inhibition of the activation and release of lysosomal
cathepsin B.