Aim: To investigate whether treatment with sodium selenate, a drug that reduces the pathological hyperphosphorylation of tau by increasing protein phosphatase 2A (PP2A) activity, would reduce spontaneous seizures, neurodegeneration and glial activation in a post- status epilepticus (SE) rat model of temporal lobe epilepsy (TLE).
Method: After four hours of SE induced by systemic kainic acid (KA) injections, or control-saline injections, young-adult male Wistar rats (n=9 /group) were given continuous sodium selenate treatment (1 mg/kg/day), with a subcutaneous osmotic mini-pump for two months. In-vivo MRI and MRS was used to assess neuronal damage and glia activation one month post-injury. Video-EEG recording was used to evaluate the seizure frequency and duration both during the treatment and after the treatment. Molecular tests were used to assess levels of hyperphosphorylated tau and related pathologies.
Results: During the treatment, the post-SE rats with saline treatment got 1.4 seizures /day, and selenate treatment could reduce the frequency to 0.1 seizures /day. After the drug washout, the effect was sustained (8.6 seizures /day in saline group vs. 2.6 seizures /day in selenate group). Selenate treatment also decreased the neurodegeneration and glial activation reflected by MRS imaging and further confirmed by immunofluorescence imaging. The selenate treatment also reduced the volume of ventricles and increased the volume of hippocampus in post-SE rats.
Conclusion: Sodium selenate treatment can reduce spontaneous seizures and biomarkers for neurodegeneration and glial activation in a post-SE rat model of TLE.