Abstract
Background and Purpose: Posttraumatic epilepsy (PTE) is a
prevalent complication of brain trauma. Current anti-epileptic drugs
available do not have satisfactory response to PTE. It is of desperate
need to explore novel therapeutic approaches for curing PTE. Our prior
work revealed that ferroptosis, a recently discovered mode of cell
death, occurs in rodent model of PTE. In the present study, we aimed to
further investigate the effect of ferrostatin-1 (Fer-1), a specific
ferroptosis inhibitor, on seizure behavior and cognitive deficit in a
mouse model of PTE.
Experimental approach: The preparation of PTE was performed by
stereotaxical injection in the somatosensory cortex region of
FeCl3. Seizure activity was assessed via Racine scoring
and electroencephalogram analysis. PTE-related cognitive function was
evaluated by novel object recognition and Morris water maze tests.
Ferroptosis-related indices including glutathione peroxidase (GPx)
activity and protein expressions of 4-hydroxynonenal (4-HNE) were
detected using a commercial kit and immunofluorescence, respectively.
Key Results: It was found that treatment with Fer-1
significantly exerted protective effects against acute seizure and
memory decline, although no evident effect on epileptic progression.
Fer-1 also exhibited good tolerability and safety as we observed that it
hardly influenced the body weight. Furthermore, it was noted that
administration of Fer-1 suppressed ferroptosis-related indices including
GPx activity and protein expressions of 4-HNE in hippocampus.
Conclusion and Implications: These data altogether indicate
that Fer-1 has potent therapeutic effects against seizures and cognitive
impairment following PTE-induced brain insult. Fer-1 may act as a
promising drug for curing PTE patients.
Keywords: posttraumatic epilepsy, seizure, cognitive
impairment, ferroptosis, ferrostatin-1, therapy