Acute Temporal Profiles of Serum Levels of UCH-L1 and GFAP and Relationships to Neuronal and Astroglial Pathology following Traumatic Brain Injury in Rats.

A number of potential traumatic brain injury (TBI) biomarkers have been proposed and evaluated in the laboratory and clinic. This study investigated the temporal profile of circulating biomarkers of astrocytic and neuronal injury over the first 24 h and relevant histopathological changes after experimental moderate TBI. Twenty male rats were randomly assigned to either moderate parasagittal fluid percussion or sham injury. Blood serum samples were collected 2 d prior to TBI (baseline) and at 3, 6, and 24 h after TBI. A single cerebrospinal fluid (CSF) sample was collected from the cisterna magna 24 h after TBI, followed by euthanasia and brain harvesting for histology. Serum and CSF samples were analyzed for neuronal (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and astroglial (glial fibrillary acidic protein [GFAP]) protein levels using enzyme-linked immunosorbent assay. Brain histology included GFAP immunostaining and Fluoro-Jade histofluorescence. Serum and CSF levels of GFAP were near zero in sham animals. Serum GFAP levels were significantly elevated at 3 and 6 h post-TBI, compared with baseline and time-matched sham values, while UCH-L1 was significantly elevated only at 3 h post-TBI. Both CSF GFAP and UCH-L1 at 24 h post-TBI were significantly elevated, compared with sham. GFAP immunohistochemistry and FJ histofluorescence of degenerating neurons were performed in the same animals after 24 h survival. Histology revealed characteristic acute neuronal degeneration in the ipsilateral hippocampus and parietal cortex and reduction in GFAP immunostaining in areas of neuronal cell loss. The data provide evidence of a causal relationship between TBI-induced acute brain pathology and circulating neuronal and glial markers, further demonstrating their role as candidate markers for TBI. Studies of relative changes in biomarker levels in CSF and serum suggest that different mechanisms may underlie the transport and/or clearance of UCH-L1 and GFAP in these two compartments.