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

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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.

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