Figure 4. Fer-1 improves PTE-associated cognitive deficits in
mice.
(A) Experiment procedure of NOR test; (B) Statistical analysis of the
exploration time, which means that the time when the mice explored the
familiar or novel object, is recorded in the NOR test. N represents the
novel object, and F represents the familiar object; (C) Statistical
analysis of discrimination index, which was calculated using the
following formula: (N-F)/(N+F) ×100%. The higher percentage of
discrimination index indicates improvement of the ability to
discriminate the novel object; (D) Illustration of effects of Fer-1 on
swimming speed from different groups; (E) Indication of swimming traces
from day 29 to day 33 after FeCl3 injection in different
groups; (F-G) Indication of effects of Fer-1 on escape latency and mean
path length, respectively in FeCl3-induced PTE; (H-I)
Indicate representative traces in the probe trial on the day 34 after
FeCl3 injection in different groups and analysis of the
number of times of crossing platform. Data were expressed as mean ± SEM
(n=6), *p<0.05 versus control group, **p<0.01 versus
control group and #p<0.05 versus
FeCl3+Vehicle group.
Figure 5. Fer-l does not display evident side effects on mice.(A) Time course of effects of Fer-1 on the body weigh from day 1 to day
34 after FeCl3 injection; (B) Cumulative analysis of
effects of Fer-1 on body weight. Data were expressed as mean ± SEM
(n=6).
Figure 6. Fer-l inhibits ferroptosis process in a mouse model of
PTE. (A) Illustration of 4-HNE immunostaining in hippocampal subregions
including CA1, CA3 and DG in different groups on the day 3 or day 34
after FeCl3 injection followed by Fer-1 treatment, Scale
bar: 100 μm; (B-C) Quantitative analysis of optical intensity of 4-HNE
in hippocampal CA3 regions on the day 3 and day 34 among different
groups; (D-E) Measurements of effects of Fer-1 on GPx activity in
FeCl3-induced PTE. Data were expressed as mean ± SEM
(n=3) **p<0.01 versus control group, ***p<0.001
versus control and ##p<0.01 versus
FeCl3+Vehicle group.
Figure 7. Fer-1 attenuates seizure-induced hippocampal damage in
FeCl3-induced PTE. (A) Illustration of Nissl staining in hippocampal
subregions including CA1, CA3 and DG in different groups on the day 3
after FeCl3 injection followed by Fer-1 treatment; (B-D)
Statistical analysis of viable neurons in CA1, CA3 and DG regions on the
day 3 among different groups; (E) Representative Nissl staining images
in CA1, CA3 and DG regions on the day 34 after FeCl3injection followed by Fer-1 treatment; (F-H) Statistical analysis of
viable neurons in CA1, CA3 and DG regions on the day 34 among different
groups. Arrow head indicates dead neurons. Scale bar: 100 μm
Figure 8. Working model. It demonstrated that Fer-1 ameliorates
seizures and improves cognitive impairments in
FeCl3-induced PTE. Inhibition of ferroptosis process
including decreases of 4-HNE level and GPx activity were possibly
involved in Fer-1’s neuroprotection.