International Neuropsychiatric Disease Journal

Aims: Although epilepsy is a common disease, the pathological process has not been sufficiently elucidated. Previous studies have reported that blood-brain barrier (BBB) damage is involved in epileptogenesis. Our aim was to non-invasively and sequentially evaluate BBB damage in a mouse model of generalised seizure, using Gadolinium (Gd)-enhanced magnetic resonance imaging using T₁ weighting (GdET₁WI). In addition, we assessed whether or not valproate (VPA) could prevent BBB damage.

Methods: Mice were kindled with the daily intraperitoneal administration of 40 mg/kg pentylenetetrazole (PTZ). After each PTZ injection, convulsive behaviours were observed, and seizures were scored from 0 to 5. Five consecutive scores of 4 or 5 were required to ensure kindling. We evaluated the changes in the BBB damage using the signal intensity (SI) ratio of GdET₁WI. The SI was sequentially measured at baseline, score 1, score 3, PTZ-kindled, and 1-week post-kindled after PTZ withdrawal. In addition, the SI was measured in mice pretreated with VPA before PTZ injection.

Results: The SI values (means±standard error of the mean) at score 1, score 3, PTZ-kindled, and post-kindled increased to 0.70%±0.22%, 7.17%±1.86%, 7.43%±1.60%, and 6.82%±1.27%, respectively, compared to baseline. All values (except at score 1) were significantly higher than those at baseline (p-value < 0.05). We did not observe significant differences between score 3 or post-kindled and PTZ-kindled. In VPA-pretreated mice, the SI significantly increased to 8.77%±1.57% compared to baseline, although convulsions were fully controlled.

Conclusion: Our data suggest that BBB damage started before PTZ-induced kindling was acquired. The BBB damage was irreversible after PTZ-induced kindling. In addition, VPA prevented epileptic convulsive seizures but could not suppress BBB damage in PTZ-kindled mice.