Fig 1.
(A) Study design, (B) the principle of experimental modelling of chronic and (C) acute brain ischemia (Fig 1B Republished from Tyurenkov IN et al. (2020) [11] under a CC BY license, with permission from OOO “Media Sphere Publishing House”, original copyright 2020). CCA–common carotid artery; ECA–external carotid artery; ICA–internal carotid artery; MCA–middle cerebral artery; MCAO–middle cerebral artery occlusion.
Fig 2.
The schematic representation of Morris water maze apparatus and the order of animal testing.
Table 1.
The severity of neurological deficit according to the Garcia and Combs & D’Alecy scales, observed 3 and 24 hours after acute brain ischemia modeling, as well as after 10 days of treatment.
Fig 3.
The number of animals that discovered and removed a foreign object during the adhesive tape test in 10- and 3-day follow-up experiments in acute brain ischemia model (A and B, correspondingly) (%).
#–p <0.05 compared to Intact; *–p <0.05 compared to placebo group (χ2 test); data shown as the number of animals that discovered and removed the adhesive tape in the group (in %).
Fig 4.
(A) The time discovered and (B) removed a foreign object during the adhesive tape test periods of experiments (after chronic brain ischemia) (s). #–p <0.05 compared to Intact; *–p <0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM.
Fig 5.
(A) Rotating rod performance in rats with acute and (B) chronic brain ischemia. #–p <0.05 compared to Intact; *–p < 0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM.
Fig 6.
Motor activity in Open field test in rats with acute brain ischemia (after 10 (A) or 3 (B) days of treatment) and in rats with chronic brain ischemia (C). #–p <0.05 compared to Intact; *–p <0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM.
Fig 7.
Morris water maze performance in rats during the course of therapy after left middle cerebral artery occlusion.
#–p <0.05 compared to Intact; *–p <0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM.
Fig 8.
Morris water maze performance in rats with chronic brain ischemia.
#–p <0.05 compared to Intact; *–p <0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM).
Fig 9.
The activity of brain antioxidant systems in rats with chronic brain ischemia.
(A) brain lactate levels; (B) brain pyruvate levels; (C) the relation of lactate to pyruvate in brain tissue; (D) brain glutathione levels; (E) malonic dialdehyde brain levels; (F) brain catalase activity; (G) brain superoxide dismutase activity; #–p <0.05 compared to Intact; *–p <0.05 compared to placebo (1-way ANOVA, t-student test with Bonferroni correction); data shown as the mean ± SEM.
Fig 10.
Representative photographs of brain slices obtained from animals with acute brain ischemia.
Brain necrosis volume at 3 days (n = 9); *–p <0.05 compared to placebo (1-way ANOVA, t-student test with Bonferroni correction); data shown as the mean ± SEM.
Fig 11.
Representative microphotographs of hippocampal slices in animals with chronic brain ischemia.
Arrows indicate the cells with roughly altered morphology, e.g. hyperchromia, triangular or polygonal form of perikaryon.
Fig 12.
Hippocampal morphology in animals with chronic brain ischemia.
NN–normal or unchanged neurons; MN–slightly modified neurons; AN–roughly altered neurons; #–p <0.05 compared to Intact; *–p <0.05 compared to placebo (Kruskal-Wallis rank analysis and the Dunn post-hoc test); data shown as the mean ± SEM.
Fig 13.
Brain content of 125I-labeled Cortexin®, Cerebrolysin® and albumin in mice.
Data shown as geometric mean (n = 15).
Fig 14.
Cortexin® receptor binding in vitro.
Data shown as the median and range (n = 2).