Development of Posiphen, an Inhibitor of Phosphorylated Tau Expression, as a Treatment of TBI
Abstract
We sought to establish preclinical efficacy of Posiphen as a treatment of traumatic brain injury (TBI). We tested Posiphen in two established animal models of TBI, the Lateral Fluid Percussion (LFP) injury model and the Controlled Cortical Impact (CCI) injury model. Both injury models produced mild TBI as defined by the lack of observed cognitive deficits in the Y maze alternation, the novel object recognition task and the Morris water maze. A 4 weeks treatment with Posiphen (2.5, 5, and 10 mg/kg i.p.) was well tolerated in rats and all doses reversed the loss of tyrosine hydroxylase induced by mild LFP in the striatum of injured rats; the highest dose additionally decreased microglial activation in the substantia nigra ipsilateral to the injury. Contrary to expectation, Posiphen at the doses used did not affect increases in amyloid precursor protein (APP) induced by injury in the hippocampus. The data indicate that Posiphen mitigated neurodegenerative consequences of mild TBI on the nigrostriatal pathway, which is affected in Parkinsons disease, without improving Alzheimers disease-related biochemical changes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1003206
Entities
People
- Maria Maccecchini