Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia–reperfusion brain injury

Yong Ming Zhu, Xue Gao, Yong Ni, Wei Li, Thomas A. Kent, Shi Gang Qiao, Chen Wang, Xiao Xuan Xu, Hui Ling Zhang

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)125-141
Number of pages17
JournalNeuroscience
Volume356
DOIs
StatePublished - Jul 25 2017

Keywords

  • astrocytes
  • astrogliosis
  • cathepsin B
  • glial scar
  • ischemic stroke
  • sevoflurane postconditioning

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia–reperfusion brain injury'. Together they form a unique fingerprint.

Cite this