Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model.
Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.
Ostrovskaya
R U
RU
Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. rita.o@postman.ru
Romanova
G A
GA
Barskov
I V
IV
Shanina
E V
EV
Gudasheva
T A
TA
Victorov
I V
IV
Voronina
T A
TA
Seredenin
S B
SB
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001931:Brain Mapping; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D020766:Intracranial Embolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004151:Dipeptides; D018697:Nootropic Agents; C103871:ethyl phenylacetyl-Pro-Gly