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  • Angiopoietin-2 in Cerebrospinal Fluid and Serum as a Predictive Biomarker for Brain Injury.

    Final Number:

    Prashant Chittiboina MD, MPH; Vijay Ganta; Keith L Soctt MD; Walter E Cromer PhD; Michael J Mathis MA; Anil Nanda MD FACS; Steven J Alexander PhD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: As roles of angiopoietins in brain injury become better understood, clinical uses for Ang-2 as a vascular stress biomarker are increasingly being explored. Several studies have established serum Ang-2 as a marker of systemic illness severity, reflecting vascular injury. Less is known about how angiopoietins, e.g. pro-inflammatory Ang-2, change in other compartments in brain injury. Since Ang-2 is stable for 24 h and resists freeze-thaw cycles it may represent a reliable and durable clinical marker for brain vascular injury.

    Methods: We compared Ang-2 in cerebrospinal fluid (CSF) collected from clinically defined subarachnoid hemorrhage (SAH, n=7) vs. controls (n=4) by immunoblotting.

    Results: We found a large (2.66-fold) and significant (p=0.043) increase in Ang-2 (range = 8-370% of control). We also evaluated Ang-2 in serum from mice undergoing middle cerebral artery occlusion for 2h / 24 hours reperfusion, (‘I/R’). We observed a significant decrease (p=0.001) in serum Ang-2 levels after I/R. Despite differences in mouse and human samples, these results suggest contrasting changes in serum and CSF Ang-2, with ischemic injury decreasing serum Ang-2 with a concomitant increase in CSF Ang-2.

    Conclusions: The results suggests that serum/CSF Ang-2 ratios may be a useful biomarker of vascular stress and temporal changes in serum/CSF ratios may predict disease severity and prognosis. Further experiments to confirm serum Ang-2 in SAH and traumatic brain injury TBI are underway to validate these markers in SAH/TBI.

    Patient Care: The results from our study may help develop predictive tests like 2D gel electrophoresis/MALDI-TOF protein identification of CSF biomarkers that may correlate closely with disease outcomes. The lessons learnt may help establish close correlation of outcome, survival, age, blood gases with Ang-1/Ang-2 levels in the acute phase after brain injury like trauma and subarachnoid hemorrhage.

    Learning Objectives: To identify changes in CSF biomarkers (e.g. angiopoietins/ Ang-1/Ang-2 ratios) that may provide novel clinical indicators both of disease severity and mechanism. to identify changes in the ratios of Angiopoietin-1 and -2 as well as their absolute levels that may represent important targets of therapy in brain injury.


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