'Therapeutic window's for multiple drug treatment of experimental cerebral ischemia in gerbils.
The effects of the following drugs: nimodipine (1 mg/kg b.w., i.p.), 2-amino-5-phosphonovaleric acid (4 mg/kg b.w., i.p.) and propentofylline (25 mg/kg b.w., i.p.), administered (alone or in combination) at the end of 15 min bilateral ischemia in gerbils were evaluated on mitochondrial superoxide dismutase (SOD), glutathione reductase (GR), glucose-6 phosphate dehydrogenase (G6PD), monoamine oxidase (MAO) activities, and thiobarbituric acid reactive material (TBARM), and brain water content at 1 hour of reperfusion. The combined treatment virtually abolished early postischemic brain edema (4.1% v.s. 0.6%) and efficiently counteracted ischemia-induced changes [decreased SOD (79% v.s. 98%), GR (52% v.s. 105%) and MAO (25% v.s. 79%), and increased TBARM (198% v.s. 108%)]. The same combination of drugs administered 15 min before ischemia had a similar effect (e.g., reduced brain swelling and lipid peroxidation) as when given at the end of ischemia, whereas a limited or absent impact was seen when the drugs were given 15 min or 1 hour after ischemia, respectively. The data suggest that (post)ischemic brain swelling and mitochondrial dysfunction can be reduced by drugs which synchronously prevent processes induced in the early stages of reperfusion.
Stanimirovic
D B
DB
Stroke Branch, NINDS, NIH, Bethesda, Maryland 20892.
Micic
D V
DV
Markovic
M
M
Spatz
M
M
Mrsulja
B B
BB
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage*; D000818:Animals; D004359:Drug Therapy, Combination; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009553:Nimodipine / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000188:drug therapy; D013997:Time Factors; D014970:Xanthines / Q000008:administration & dosage*
D014970:Xanthines; D009553:Nimodipine; C032114:propentofylline; D015763:2-Amino-5-phosphonovalerate