Edaravone Attenuates Brain Edema and Neurologic Deficits in a Rat Model of Acute Intracerebral Hemorrhage

Abstract

Background and Purpose-Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury. Methods-These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 L autologous whole blood (ICH), FeCl 2 , or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2Ј-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron-and thrombin-induced brain injury. Results-Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (PϽ0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (PϽ0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2Ј-deoxyguanosine and reduced iron-and thrombin-induced brain injury. Conclusions-Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron-and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

“…It has been used clinically to reduce neuronal damage resulting from cerebral ischemic stroke in Japan and China (Nakamura et al 2008). In addition, edaravone has displayed its protective effects in a variety of brain diseases, including traumatic brain injury (Ohta et al 2013), Alzheimer's disease (Yan et al 2012), and Parkinson's disease (Yuan et al 2008).…”

Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke

“…In a rat model of acute intracerebral hemorrhage, the administration of edaravone attenuated neurological deficits, brain edema, oxidative injury and iron-and thrombin-induced neuronal injury (49). Edaravone, therefore, inhibited hemorrhagic transformation, while attenuating brain injury subsequent to hemorrhage.…”

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction

“…ICH is an often-fatal stroke subtype (24) and accounts for 8-15% of all strokes in Western populations and 20-30% in Asian populations (25). ICH frequently produces severe neurologic deficits due to secondary brain edema (24).…”

“…Edaravone was found to attenuate ICH-induced brain edema, neurologic deficits and oxidative injury in rats. In addition, edaravone was found to reduce iron-and thrombininduced brain injury (24).…”