Remote ischemic post-conditioning improves neurological function by AQP4 down-regulation in astrocytes

Behav Brain Res. 2015 Aug 1:289:1-8. doi: 10.1016/j.bbr.2015.04.024. Epub 2015 Apr 21.

Abstract

Cerebral ischemia is a primary cause of human death and long-term disability. Previous studies have suggested that remote ischemic post-conditioning (RIPC) is a potential useful tool for cerebral ischemic treatment. However, the protective mechanism of RIPC is not very clear. This study verified the hypothesis that, in remote post-conditioning of cerebral ischemic rats, down-regulation of aquaporin 4 (AQP4), which is an important player for water hemostasis in astrocytes, could attenuate cerebral damage after transient middle cerebral artery occlusion (MCAO). In this study, RIPC model was established after MCAO. Each hind limb of rat was clamped by small rubber tubes for 10 min, and then the tubes were opened for 10 min. The clamping and opening were operated for a total of three cycles to block the hind limbs blood flow. The results showed that, RIPC could significantly improve neurological function, decrease the percentage of the infarct volume and edema, and elevate the integrity of blood-brain barrier (BBB). In addition, the numbers of AQP4 and glial fibrillary acidic protein (GFAP) positive cells were significantly lower in the RIPC group. Moreover, we found that AQP4 expression decreased in response to ischemia/reperfusion in the RIPC group. Our findings indicated that RIPC could attenuate focal cerebral ischemia/reperfusion injury, and the neuroprotective mechanism was related with the down-regulation of AQP4 in astrocytes.

Keywords: Aquaporin 4; Cerebral ischemic stroke; Middle cerebral artery occlusion; Remote ischemic post-conditioning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Aquaporin 4 / metabolism*
  • Astrocytes / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain / blood supply*
  • Brain / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Down-Regulation
  • Female
  • Humans
  • Infarction, Middle Cerebral Artery
  • Ischemic Postconditioning*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / therapy

Substances

  • Aqp4 protein, rat
  • Aquaporin 4