Fingolimod exerts neuroprotective effects in a mouse model of intracerebral hemorrhage

Brain Res. 2014 Mar 25:1555:89-96. doi: 10.1016/j.brainres.2014.01.048. Epub 2014 Feb 3.

Abstract

Recent studies have shown that fingolimod (FTY720) is neuroprotective in CNS injury models of cerebral ischemia and spinal cord injury. The purpose of the study was to examine the effect of fingolimod in a mouse model of intracerebral hemorrhage. ICH was produced in adult CD1 mice by injecting collagenase VII-S (0.5 µL, 0.06 U) into the basal ganglia. Fingolimod (or saline) was given 30 min after surgery and once daily for two days. Three days after intracerebral hemorrhage, brain edema, hematoma volume and the number of apoptotic cells were quantified. In another cohort of mice, brain atrophy was evaluated two weeks following intracerebral hemorrhage. Neurobehavioral tests were performed on the 3rd, the 7th and the 14th day. Fingolimod significantly decreased edema, apoptosis and brain atrophy. More importantly, fingolimod enhanced neurobehavioral recovery. Preliminary experiments showed no difference in the number of inflammatory (CD68-positive) cells between the two groups. In conclusion, fingolimod exerts protective effects in a mouse model of intracerebral hemorrhage; the mechanisms underlying these neuroprotective effects deserve further study.

Keywords: FTY720; Intracerebral hemorrhage; Neuroprotection; Sphingosine 1-phosphate; Stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Edema / complications
  • Brain Edema / drug therapy
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Disease Models, Animal
  • Fingolimod Hydrochloride
  • Hematoma / drug therapy
  • Male
  • Mice
  • Neuroprotective Agents / therapeutic use*
  • Propylene Glycols / therapeutic use*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Weight Loss / drug effects

Substances

  • Neuroprotective Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine