Seizures are a druggable mechanistic link between TBI and subsequent tauopathy

Traumatic brain injury (TBI) is a prominent risk factor for dementias including tauopathies like chronic traumatic encephalopathy (CTE). The mechanisms that promote prion-like spreading of Tau aggregates after TBI are not fully understood, in part due to lack of tractable animal models. Here, we test the putative role of seizures in promoting the spread of tauopathy. We introduce 'tauopathy reporter' zebrafish expressing a genetically encoded fluorescent Tau biosensor that reliably reports accumulation of human Tau species when seeded via intraventricular brain injections. Subjecting zebrafish larvae to a novel TBI paradigm produced various TBI features including cell death, post-traumatic seizures, and Tau inclusions. Bath application of dynamin inhibitors or anticonvulsant drugs rescued TBI-induced tauopathy and cell death. These data suggest a role for seizure activity in the prion-like seeding and spreading of tauopathy following TBI. Further work is warranted regarding anti-convulsants that dampen post-traumatic seizures as a route to moderating subsequent tauopathy.

Automated summary

Research suggests that traumatic brain injury (TBI) may contribute to tauopathy and subsequent dementia, with seizures potentially playing a key role in promoting the spread of Tau aggregates. Using a zebrafish model, it was found that bath application of dynamin inhibitors or anticonvulsant drugs could rescue TBI-induced tauopathy and cell death. Further exploration is needed to investigate the potential of anti-convulsants in mitigating post-traumatic seizures and tauopathy.