Plasma-Type Gelsolin Is Decreased in Human Blood and Cerebrospinal Fluid After Subarachnoid Hemorrhage

• Published in: Stroke (1970) Vol. 42; no. 12; pp. 3624 - 3627
• Main Authors: CHOU, Sherry H.-Y, LEE, Po-Shun, MINGMING NING, KONIGSBERG, Rachael G, GALLACCI, Dana, CHIOU, Terry, ARAI, Ken, SIMMONS, Suzanne, BAUER, David, FESKE, Steven K, LO, Eng H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-12-2011
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Female; Gelsolin - blood; Gelsolin - cerebrospinal fluid; Gelsolin - metabolism; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Hydrocephalus - blood; Hydrocephalus - cerebrospinal fluid; Male; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - cerebrospinal fluid; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Subarachnoid Hemorrhage - blood; Subarachnoid Hemorrhage - cerebrospinal fluid; Subarachnoid Hemorrhage - metabolism; Vascular diseases and vascular malformations of the nervous system; Human; Stroke; Nervous system diseases; Subarachnoid hemorrhage; gelsolin; Cardiovascular disease; Cerebrospinal fluid; biomarker; Cerebral disorder; Vascular disease; Central nervous system disease; Metalloproteinase; matrix metalloproteinases; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.111.631135

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).
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.
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).
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.