A pre-existing chronic Toxoplasma gondii infection promotes epileptogenesis and neuropathology in a mouse model of mesial temporal lobe epilepsy

Objective

There is initial evidence that the common neurotropic parasite Toxoplasma gondii is a risk factor for the development of epilepsy; however, whether it influences epileptogenesis is unknown. This study investigated whether a pre-existing chronic T. gondii infection alters epileptogenesis and neuropathology in a mouse model of mesial temporal lobe epilepsy.

Methods

Male and female C57BL/6Jax mice were intraperitoneally administered T. gondii tachyzoites or vehicle control. After 6 weeks, mice underwent self-sustained electrical status epilepticus (SSSE) through an implanted bipolar electrode, or a sham procedure. Continuous video-EEG recordings were taken 0–4- and 12–16-weeks post-SSSE to detect spontaneous seizures. Neuroinflammatory markers were assessed within 1-week post-SSSE, behavior testing was done at 8–12 weeks post-SSSE, and ex vivo MRI was conducted at 16 weeks post-SSSE.

Results

Male T. gondii + SSSE mice had an increased incidence of epilepsy compared to Vehicle + SSSE, while female T. gondii + SSSE mice had worse seizure severity compared to non-infected SSSE mice. There was amplified neuroinflammation in both male and female T. gondii + SSSE mice compared to Vehicle + SSSE mice. T. gondii infection in the absence of SSSE also resulted in epilepsy and neuroinflammation. MRI revealed abnormalities in brain morphology in T. gondii + SSSE male and female mice and changes in white matter integrity in male T. gondii + SSSE mice, compared to both non-infected SSSE and T. gondii control mice. SSSE and T. gondii infection impacted anxiety and spatial memory in males, and anxiety and social behavior in females.

Interpretation

These findings demonstrate that a chronic T. gondii infection can result in epilepsy, and that a pre-existing T. gondii infection exacerbates epileptogenesis following a brain insult, in mice.