Acute Neurovascular Inflammatory Profile in Patients with Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from intracranial aneurysm rupture, leading to the accumulation of blood between the arachnoid and pia mater. The blood breakdown products and damage-associated molecule patterns (DAMPs), which are released as a result of vascular and cellular compromise following aneurysm rupture, elicit local endothelial reactions leading to the narrowing of cerebral arteries and ischemia. In addition, vascular inflammation, characterized by activated endothelial cells, perpetuates disruption of the neurovascular unit and the blood-brain barrier. The uncertain prognosis of aSAH patients contributes to the necessity of a fluid biomarker that can serve as a valuable adjunct to radiological and clinical evaluation. Limited studies have investigated vascular inflammation and angiogenic protein expression following aSAH. Reliable markers of the vascular inflammatory and angiogenic response associated with aSAH may allow for the earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. We investigated whether vascular inflammatory and angiogenesis signaling proteins may serve as potential biomarkers of aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls as well as hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of vascular inflammatory and angiogenesis proteins. Protein measurement was carried out using electrochemiluminescence. The area under the curve (AUC) was calculated using receiver operating characteristics (ROC) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, patients were grouped by Glasgow Outcome Score-Extended at 3 months post-injury to determine the correlation between vascular inflammatory protein levels and clinical outcome measures. aSAH subjects demonstrated elevated vascular inflammatory protein levels in serum and CSF when compared to controls. Certain vascular injury and angiogenic proteins were found to be promising biomarkers of inflammatory response in aSAH in the CSF and serum. In particular, elevated levels of serum amyloid-alpha (SAA) were found to be correlated with unfavorable outcomes following aSAH. Determination of these protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.