Naslov
LIGA20, a lyso derivative of ganglioside GM1, given orally after cortical thrombosis reduces infarct size and associated cognition deficit

Autori
Kharlamov, August ; Živković, Ilija ; Guidotti, Alessandro ; Costa Emilio

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 91 (1994), 14; 6303-6307

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Liga20 ; ganglioside GM! ; cortical trombosis ; cognition deficit

Sažetak
A bilateral photochemically induced thrombotic lesion of rat sensorimotor cortex (approximate to 3 mm in diameter and 25 mm(3) in volume) is associated with a persistent cognition (learning and memory) deficit, which was evaluated with water maze tasks. The N-dichloroacetylsphingosine derivative of lysoGM1 (LIGA20) administered after the lesion either i.v., or per os reduces the infarct size by 30-40% and attenuates the associated cognition deficits, presumably by limiting the extent of damage of neurons at risk located in the surroundings of the infarcted core (i.e., area penumbra). The LIGA20 protection is dose and time dependent. Maximal protection is afforded by a single dose of LIGA20 of 34 mu mol/kg i.v. 1 hr after lesion or by a dose of 270 mu mol/kg per os when administered 1 hr and 24 hr after the lesion. The protective effect of LIGA20 can be observed when the drug is administered i.v. up to 6 hr after the lesion. The protective efficacy of the oral administration of LIGA20 is related to its physicochemical properties, which, unlike those of GM1, allow absorption from the gastrointestinal tract. LIGA20 given orally reaches the brain promptly and rapidly inserts into the neuronal membranes. Here, by an unknown molecular mechanism, LIGA20 selectively reduces the pathological amplification of Ca2+ signaling elicited by persistent stimulation of ionotropic glutamate receptors in the area penumbra.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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