Abstracts

Rationale: Hyperphosphorylated tau has been implicated in the pathogenesis of a variety of neurodegenerative disorders, including traumatic brain injury (TBI) and epilepsy. Here we investigated whether treatment with sodium selenate, a drug that reduces the pathological hyperphosphorylation of tau by increasing PP2A activity, would reduce neurodegeneration, functional impairments, and post-traumatic epilepsy in a rat fluid percussion model of TBI. Methods: After a severe fluid percussion injury, or sham-injury, young-adult male Long-Evans rats were given continuous sodium selenate treatment (1 mg/kg/day), administered via subcutaneous osmotic mini-pump, for a period of three months. Anatomical magnetic resonance imaging, diffusion weighted imaging and diffusion tensor imaging were used to assess structural damage and axonal injury one week, one month, and three months post-injury and compared to a baseline pre-injury scan. Cognitive, motor, and emotional impairments were assessed at three months post-injury. After behavioural testing rats were implanted with recording electrodes and continuously monitored for seizure activity for two weeks. Immunohistochemical and western-blot analyses were used to assess levels of PP2A, hyperphosphorylated tau, and other related pathologies. Results: Rats treated with sodium selenate treatment had significantly reduced hyperphosphorylated tau, cortical loss on anatomical MRI, axonal injury on diffusion weighted imaging and diffusion tensor imaging (Figure 1), and behavioural impairments after a severe lateral fluid percussion injury in the rat. Conclusions: These data indicate that sodium selenate has neuroprotective effects in a rat model of TBI, and may represent a novel approach to TBI treatment to reduce adverse neurodegenerative and neurobehavioural outcomes.