Neuroprotective effects of guanosine on stroke models in vitro and in vivo.
Deprivation of oxygen and glucose for 5h induces apoptosis in SH-SY5Y neuroblastoma cell cultures. After combined glucose and oxygen deprivation (CGOD) addition of guanosine (100 microM), a non-adenine-based purine nucleoside, significantly reduced the proportion of cells undergoing apoptosis. To determine whether guanosine was also neuroprotective in vivo, we undertook middle cerebral artery occlusion (MCAo) on male Wistar rats and administered guanosine (8mg/kg), intraperitoneally, or saline (vehicle control) daily for 7 days. Guanosine prolonged rat survival and decreased both neurological deficits and tissue damage resulting from MCAo. These data are the first to demonstrate that guanosine protects neurons from the effects of CGOD even when administered 5h after the stimulus, and is neuroprotective in experimental stroke in rats.
Chang
Ruby
R
Department of Neurosurgery, McMaster University, Health Sciences Centre, 4N71B, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Algird
Almunder
A
Bau
Christian
C
Rathbone
Michel P
MP
Jiang
Shucui
S
D000818:Animals; D002461:Cell Line, Transformed; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D006151:Guanosine / Q000627:therapeutic use*; D000860:Hypoxia; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D006151:Guanosine; D005947:Glucose