Neurosurgery and Neuroscience

Edaravone is a free radical scavenger, which is the first clinical drug for neuroprotection in the world which has been approved from 2001 in most ischemic stroke patients in Japan, and some of China and India. Edaravone scavenges hydroxyl radicals both in hydrophilic and hydrophobic conditions and is especially useful in thrombolytic therapy with tissue plasminogen activator (tPA). Combination therapy of Edaravone with tPA greatly increased survival of stroke animals, reduced infarct size, and inhibited molecular markers of oxidative damage in lipid, protein and DNA. Use of Edaravone greatly reduced hemorrhagic transformation accompanied by tPA treatment, and may also extend therapeutic time window with tPA therapy for more than 4.5 hrs in human stroke patients for preserving neurovascular unit (NVU). An intensive Edaravone therapy for 3 days now showed a favorite recovery in 3 European countries. Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease caused by selective death of motor neurons. Among our own 390 ALS patients, 4.1% show familial ALS (FALS), in which 50% is associated with missense mutations of SOD1, 25% were TDP43 and FUS mutations, and 6.3% is an optineurin mutation. Although the underlying mechanism of ALS has not yet been fully clarified, several reports have implicated the involvement of oxidative stress under selective death of motor neurons in both ALS patients and animal models. A recent multicenter prospective double-blind placebo-control clinical trial with edaravone for ALS patients conducted in Japan showed a positive effect for delaying the clinical score (ALS FRS-R) during the course of examination (24 weeks). Serious or critical adverse eff ect was not noted in this clinical trial. Of particular was that this clinical benefit of edaravone was shown as an add-on therapy after anti-glutamatergic riluzole. These data strongly suggest a potential underlying mechanism of oxidative stress in ALS and a clinical delay by a free radical scavenger. These translational studies on a free radical scavenger Edaravone allowed governmental permissions both for acute ischemic stroke after 2001 and for ALS after 2015. Edaravone was approved for ALS at 2015 in Japan, 2016 in Korea, and 2017 in USA.