mGluR1 characteristic in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage

Glutamate receptor-mediated excitotoxicity plays crucial role in aneurysmal subarachnoid hemorrhage (aSAH). Truncation of metabotropic glutamate receptor 1 (mGluR1) is a key step in excitotoxicity, whether it occurs in aSAH patients is unclear. This study attempts to investigate mGluR1 characteristic in cerebrospinal fluid (CSF) of aSAH patients.

CSF samples from normal pressure hydrocephalus (NPH) and aSAH patients were obtained via the external ventricular drainage, collected by centrifugation, and stored at −80℃ until analyze by Western Blot and Enzyme-linked Immunosorbent Assay (ELISA). The clinical and hemorrhage severity (Hunt and Hess, HH grade; World Federation of Neurological Surgeons, WFNS grade; Fisher grade), and clinical outcome (Glasgow outcome scale, GOS) were retrieved from aSAH patients’ records.

In the early exploration phase (3 aSAH vs 3 NPH), Western blot analysis of CSF samples showed that the protein band detected with the anti-mGluR1_300-400 antibody is 95 kDa, while that detected with the anti-mGluR1_1159-1171 antibody is 38 kDa, indicating that truncation of mGluR1 occurred in CSF of aSAH patients, but not observed in CSF of control patients. The semi-quantitative analysis of mGluR1 protein band (38 and 95 kDa) and the ELISA measured mGluR1 level show a similar trend of change. Next, the mGluR1 level in CSF of 244 aSAH patients was determined by ELISA analysis. Initial level of mGluR1 was significantly higher in aSAH patients with Fisher score of 3–4 versus 1–2, WFNS grade of Ⅳ-Ⅴ versus Ⅰ-Ⅲ, HH grade of Ⅳ-Ⅴ versus Ⅰ-Ⅲ, and with GOS score of 1–3 (poor outcome) versus 4–5 (good outcome). The multivariable logistic regression analysis showed that initial level of mGluR1 was associated with the occurrence of poor outcome, resulted in an area under receiver-operator characteristic curve (ROC) of 0.837 in predicting poor outcome.

These findings indicate that early high level of mGluR1 truncation in CSF could serve as a potential predictor of poor outcome in aSAH patients.