Toxicological sciences : an official journal of the Society of Toxicology
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Glutamate excitotoxicity plays a key role in the etiology of a variety of neurological, psychiatric, and neurodegenerative disorders. The goal of this study was to investigate spatiotemporal distribution in the brain and cerebrospinal fluid (CSF) concentrations of ubiquitin C-terminal hydrolase-1 (UCH-L1), glial fibrillary acidic protein (GFAP), αII-spectrin breakdown products (SBDP150, SBDP145, and SBDP120), and their relationship to neuropathology in an animal model of kainic acid (KA) excitotoxicity. Triple fluorescent labeling and Fluoro-Jade C staining revealed a reactive gliosis in brain and specific localization of degenerating neurons in hippocampus and entorhinal cortex of KA-treated rats. ⋯ The temporal increase in CSF biomarkers correlated with brain tissue distribution and neurodegeneration. This study provided evidence supporting the use of CSF levels of glial and neuronal protein biomarkers to assess neurotoxic damage in preclinical animal models that could prove potentially translational to the clinic. The molecular nature of these biomarkers can provide critical information on the underlying mechanisms of neurotoxicity that might facilitate the development of novel drugs and allow physicians to monitor drug safety.