Rapamycin protects against early brain injury independent of cerebral blood flow changes in a mouse model of subarachnoid haemorrhage

Clin Exp Pharmacol Physiol. 2018 Aug;45(8):859-862. doi: 10.1111/1440-1681.12950.

Abstract

We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Pretreatment with rapamycin, an mTOR kinase inhibitor, resulted in better recovery from cerebral hypoxia early after SAH than control (P < .05), while the values of peak flow velocity in the middle cerebral artery did not change significantly (P > .05). Average distance travelled and the ratio of central-area distance/total travelled distance determined by open-field test after day 14 was significantly higher in mice pretreated with rapamycin than in control mice (P < .05). Inhibition of the mTOR pathway could be protective against post-SAH early brain injury, ameliorating brain tissue hypoxia and locomotor hypoactivity.

Keywords: cerebral blood flow; early brain injury; mammalian target of rapamycin; mouse model; subarachnoid haemorrhage.

Publication types

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

MeSH terms

  • Animals
  • Brain Ischemia / prevention & control*
  • Cerebrovascular Circulation / drug effects*
  • Male
  • Mice
  • Neuroprotective Agents / therapeutic use*
  • Sirolimus / therapeutic use*
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism
  • Subarachnoid Hemorrhage / physiopathology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Neuroprotective Agents
  • TOR Serine-Threonine Kinases
  • Sirolimus