Low-dose edaravone injection into the clamped aorta prevents ischemic spinal cord injury.
Previous studies have indicated that high-dose intravenous edaravone (3-10mg/kg) protects against ischemic spinal cord injury. This study examined whether direct injection of low-dose edaravone into the clamped segment of the aorta prevents ischemic spinal cord injury. Spinal cord ischemia was induced in rabbits by aortic clamping below the renal artery and above the aortic bifurcation for 15min at normothermia. In groups A and B, 3 and 1mg/kg of edaravone, respectively, was injected into the clamped segment of the aorta immediately following aortic clamping. In group C, saline was injected. Neurological function was assessed at 8, 24, and 48hr and 7 days after reperfusion with Tarlov criteria. The spinal cord was histologically examined at 7 days with hematoxylin-eosin staining and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The Tarlov score remained grade 4 throughout the period in groups A and B, whereas it dropped to grade 0 or 1 at 7 days in group C, significantly higher in the former two groups. The number of intact motor neurons was significantly greater in groups A and B with less necrotic motor neurons than in group C. There was no significant difference in terms of spinal cord protection between groups A and B. There was no TUNEL-positive neuron in any group, indicating the absence of apoptosis. Low-dose intra-aortic edaravone injection prevents immediate neuronal injury by reducing neuronal cell damage in the early stage as well as delayed neuronal injury at 7 days.
Hamaishi
Makoto
M
Division of Clinical Medical Science, Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. mhtaker@yahoo.co.jp
Orihashi
Kazumasa
K
Isaka
Mitsuhiro
M
Kumagai
Hajime
H
Takahashi
Shinya
S
Okada
Kenji
K
Ohtaki
Megu
M
Sueda
Taijiro
T
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001011:Aorta / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects; D003250:Constriction; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling; D007269:Injections, Intra-Arterial; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011817:Rabbits; D012720:Severity of Illness Index; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine