Orally administered glycolipid derivative LIGA20 reduces infarct volume and behavioral impairment after focal cerebral ischemia.
The efficacy of p.o. semisynthetic glycolipid LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-aceta mide-4-trans- octadecene) treatment in stroke was studied in a permanent left middle cerebral artery occlusion model in the rat. A dose-dependent increase of plasma LIGA20 and its presence in the brain were documented after p.o. drug application. Oral administration of 50 to 200 mg/kg of LIGA20, initiated 24 hr before middle cerebral artery occlusion and continued for 7 days, reduced the motor and cognitive impairment after the stroke, measured by the rotarod and the passive avoidance test, respectively. The 10-mg/kg dose was effective when given i.v. but not p.o. Oral treatment with 100 mg/kg of LIGA20 reduced the infarct size in the cortex but not in the ischemic core (the striatum). No biochemical or behavioral adverse effects of LIGA20 treatment were observed. Further studies are needed to evaluate the full therapeutic potential of this compound.
Seren
M S
MS
FIDIA Research Laboratories, Abano Terme (PD), Italy.
Lazzaro
A
A
Yang
C L
CL
Canella
R
R
Bassan
M
M
Zanoni
R
R
Manev
H
H
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C086919:LIGA 20; D005677:G(M1) Ganglioside; D013110:Sphingosine