title: Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after subarachnoid hemorrhage.
abstract: OBJECTIVE
  Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these 2 phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type gelsolin (pGSN).
  
  
  METHODS
  We enrolled 42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked immunosorbent assay, Western blotting, and zymography were used to quantify pGSN and MMP-9.
  
  
  RESULTS
  In CSF, pGSN was lower in SAH compared with control subjects on post-SAH Days 2 to 3 (P=0.0007), 4 to 5 (P=0.041), and 10 to 14 (P=0.007). In blood, pGSN decreased over time (P=0.001) and was lower in SAH compared with control subjects on post-SAH Days 4 to 5 (P=0.037), 6 to 7 (P=0.006), and 10 to 14 (P=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH Day 7 (r=-0.38; P=0.05).
  
  
  CONCLUSIONS
  SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP-pGSN signaling in SAH.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sherry H-Y
authors.initials: SH
authors.lastname: Chou
authors.forename: Po-Shun
authors.initials: PS
authors.lastname: Lee
authors.forename: Rachael G
authors.initials: RG
authors.lastname: Konigsberg
authors.forename: Dana
authors.initials: D
authors.lastname: Gallacci
authors.forename: Terry
authors.initials: T
authors.lastname: Chiou
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.forename: Suzanne
authors.initials: S
authors.lastname: Simmons
authors.forename: David
authors.initials: D
authors.lastname: Bauer
authors.forename: Steven K
authors.initials: SK
authors.lastname: Feske
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: MingMing
authors.initials: M
authors.lastname: Ning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D018260:Gelsolin / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D006849:Hydrocephalus / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018260:Gelsolin; D020780:Matrix Metalloproteinase 9