title: Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.
abstract: OBJECTIVE
  During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro.
  
  
  METHODS
  CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-beta1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies.
  
  
  RESULTS
  PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs.
  
  
  CONCLUSIONS
  Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.
authors.affiliation: Department of Anesthesiology, Duke University, Durham, NC, USA. borel001@mc.duke.edu
authors.forename: Cecil O
authors.initials: CO
authors.lastname: Borel
authors.forename: Andy
authors.initials: A
authors.lastname: McKee
authors.forename: Augusto
authors.initials: A
authors.lastname: Parra
authors.forename: Michael M
authors.initials: MM
authors.lastname: Haglund
authors.forename: Amy
authors.initials: A
authors.lastname: Solan
authors.forename: Vikas
authors.initials: V
authors.lastname: Prabhakar
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Laura
authors.initials: L
authors.lastname: Niklason
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008222:Lymphokines / Q000134:cerebrospinal fluid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D010841:Pia Mater / Q000098:blood supply / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000150:complications* / Q000473:pathology; D013927:Thrombosis / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D000906:Antibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095477:platelet-derived growth factor AB