Local carboxyfullerene protects cortical infarction in rat brain.
The neuroprotective effect of carboxyfullerene, a water-soluble derivative of fullerene, on the transient focal ischemia-reperfusion injury was investigated in rat brain. A focal infarction in the cerebral cortex was consistently observed 24 h after a 60-min transient ischemia by occlusion of the right middle cerebral artery and bilateral common carotid arteries. The fluorescent end products of lipid peroxidation were increased in the infarcted cortical area. Furthermore, the GSH level was decreased in the infarcted cortex. Carboxyfullerene was either intravenously (6 mg/kg) or intracerebroventricularly (0.1, 0.3 mg per rat) infused to the chloral hydrate-anesthetized Sprague-Dawley rats 30 min prior to transient ischemia-reperfusion. No protection of cortical infarction was observed after intravenous administration of carboxyfullerene. In contrast, intracerebroventricular infusion of carboxyfullerene not only attenuated cortical infarction but also prevented both the elevated lipid peroxidation and the depleted GSH level induced by transient ischemia-reperfusion. Adverse behavioral changes were simultaneously observed in rats receiving intracerebroventricular infusion of carboxyfullerene (0.3 mg per rat), including writhing accompanied by trunk stretch and even death. Our data suggest that intracerebroventricular infusion of carboxyfullerene may attenuate oxidative injuries by transient ischemia-reperfusion. Nevertheless, undesired side effects may limit the usefulness of carboxyfullerene in biological organisms.
Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan, ROC.
Anya Maan-Yuh
AM
Lin
Su-Feng
SF
Fang
Shin-Zong
SZ
Lin
Cheng-Kong
CK
Chou
Tieng-Yau
TY
Luh
Low-Tone
LT
Ho
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002244:Carbon / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D008054:Lipid Peroxides; D018696:Neuroprotective Agents; D002244:Carbon; D005978:Glutathione