Cerebral ischemia-reperfusion injury: a novel therapeutic approach with TAK-218.
The goal of the present study was to evaluate the potential neuroprotective effect of TAK-218 in an in vivo rat focal cerebral ischemia/reperfusion model. TAK-218 is a novel compound with multiple antiischemic properties, including suppression of aberrant dopamine release, modulation of sodium channels, and inhibition of lipid peroxidation. The study was a blinded, randomized, placebo-controlled study of TAK-218 in a three-vessel focal ischemic rat model. A total of 22 rats were randomly assigned to the treatment or placebo group. Animals were injected intrapertoneally with either a 2 mg/kg dose of drug or saline at 2 hours after reperfusion. Infarction volume was measured with use of 2,3,5-triphenyltetrazolium chloride. Total adjusted infarction volume in treated animals decreased by 10%. With use of a statistical analysis requiring 80% power with a 20% reduction desired effect, there was no statistically significant difference in the end-point of infarction volume between drug and placebo treatment groups. In light of the proven efficacy of thrombolytic therapy for acute stroke, it is now desirable to test neuroprotective agents during the 3-hour therapeutic window after ischemia. Further research is necessary to discern if a therapeutic agent with multiple antiischemic properties may provide a more robust neuroprotective effect than an agent with a single neuroprotective action.
Solenski
N J
NJ
Department of Neurology, Health Sciences Center, University of Virginia, Charlottesville 22908, USA.
diPierro
C G
CG
Kassell
N F
NF
Helm
G A
GA
D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D006439:Hemodynamics / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
D001572:Benzofurans; D018696:Neuroprotective Agents; C104755:TAK 218