Elevation of CSF Sortilin Following Subarachnoid Hemorrhage in Patients and Experimental Model Rats

Subarachnoid hemorrhage (SAH) can cause acute neuronal injury and chronic neurocognitive deficits; biomarkers reflecting its associated neuronal injury are of potential prognostic value. Sortilin, a member of the vacuolar protein sorting 10p (Vps10p) family, is enriched in neurons and is likely involved in neurodegenerative diseases. Here, we explored sortilin in the cerebrospinal fluid (CSF) as a potential biomarker for early neuronal injury after SAH. Sortilin levels in the CSF of SAH patients (n = 11) and controls (n = 6) were analyzed by immunoblot. SAH rats surviving 3-72 h (h) were evaluated neurologically, with their brain and CSF samples examined histologically and biochemically. Sortilin protein ~100 kDa was detected in the CSF from SAH patients only, with its levels correlated to Hunt-Hess scale. Rats in the SAH groups showed poorer Garcia score and beam balancing capability than sham controls. Sortilin ~100 kDa was detectable in the CSF of the SAH, but not sham, animals. Levels of sortilin ~100 kDa and fragments ~40 kDa in cortical lysates were elevated in the SAH relative to control rats. Levels of cortical glial fibrillary acidic protein (GFAP) were also elevated in the SAH rats. In immunohistochemistry, the pattern of sortilin labeling in the brain was largely comparable between the SAH and control rats, whereas an increased astrocytic GFAP immunolabeling was evident in the former. Together, these results suggest that SAH can cause an early and remarkable rise of sortilin products in CSF, likely reflecting neuronal change. Sortilin could be further explored as a potential biomarker in some brain disorders.