title: Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis.
abstract: BACKGROUND
  Delayed cerebral ischemia (DCI) contributes to morbidity following aneurysmal subarachnoid hemorrhage; however, its etiology remains poorly understood. DCI is not only a consequence of angiographic vasospasm, but also involves microthrombosis and neuroinflammation, two events with unexplained phenomenology. The vascular endothelial glycocalyx mediates platelet aggregation and endothelial cell-leukocyte interactions and may play an important role in DCI pathogenesis.
  
  
  METHODS
  We present a case series in which we conducted multiplex and singlet enzyme-linked immunosorbent assays of endothelial, glycocalyx, inflammatory, and neuroinjury proteins in both CSF and plasma in three patients during active DCI following SAH. Samples were obtained at baseline following surgical repair of SAH, and again at DCI onset. CSF was sampled at the same time points from in situ external ventricular drains.
  
  
  RESULTS
  DCI was associated with significant elevations of soluble markers of endotheliopathy, including vascular adhesion protein-1, soluble fractions of endothelial cell adhesion molecules (CAMs), procoagulant tissue factor, and specific markers of glycocalyx injury, including syndecan-1, and CD44. These phenomena were also associated with an elevation of both circulating and CSF matrix metalloproteinases, which are known to cleave components of the glycocalyx. Elevation of vascular CAM-1 in the CSF with DCI indicated these events were possibly associated with the breakdown of brain microvasculature integrity.
  
  
  CONCLUSIONS
  These preliminary data support the hypothesis that glycocalyx injury occurs in SAH, and might contribute to DCI by regulating cerebral microthrombosis and delayed neuroinflammation.
authors.affiliation: Clinician-Investigator Program, Department of Anesthesia, University of Toronto, Toronto, ON, Canada. Josh.bell@mail.utoronto.ca.
authors.forename: Josh D
authors.initials: JD
authors.lastname: Bell
authors.affiliation: Defense Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada.
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Rhind
authors.affiliation: Defense Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Di Battista
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesia, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002545:Brain Ischemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D019276:Glycocalyx; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications*; D008297:Male; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000209:etiology; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: Cerebral ischemia; Endothelial cell; Glycocalyx; Inflammation; Subarachnoid hemorrhage; Thrombosis