Cerebrospinal fluid protein biomarker panel for assessment of neurotoxicity induced by kainic acid in rats.

摘要: Glutamate excitotoxicity plays a key role in the etiology of variety neurological, psychiatric, and neurodegenerative disorders. The goal this study was to investigate spatiotemporal distribution brain cerebrospinal fluid (CSF) concentrations ubiquitin C-terminal hydrolase-1 (UCH-L1), glial fibrillary acidic protein (GFAP), αII-spectrin breakdown products (SBDP150, SBDP145, SBDP120), their relationship neuropathology an animal model kainic acid (KA) excitotoxicity. Triple fluorescent labeling Fluoro-Jade C staining revealed reactive gliosis specific localization degenerating neurons hippocampus entorhinal cortex KA-treated rats. Immunohistochemistry showed upregulation GFAP expression beginning 24h post KA injection peaking at 48h. At these time points concurrent with extensive neurodegeneration all SBDPs were observed throughout brain. injection, loss structural integrity cellular UCH-L1 that correlated increase immunopositive material extracellular matrix. CSF levels UCH-L1, GFAP, significantly increased animals compared controls. temporal biomarkers tissue neurodegeneration. This provided evidence supporting use neuronal assess neurotoxic damage preclinical models could prove potentially translational clinic. molecular nature can provide critical information on underlying mechanisms neurotoxicity might facilitate development novel drugs allow physicians monitor drug safety.