title: Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man.
abstract: The relation between cerebral ischemia and local release of angiogenic factors was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular, cisternal, and lumbar) were analyzed in 15 patients surgically treated for ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V). Data were related to brain Po2 (Pbro2) and cerebral energy metabolites (extracellular lactate, pyruvate, glutamate, and glycerin concentrations) as well as clinical and radiologic reference data. Delayed impairment of cerebral perfusion secondary to progressive microcirculatory alterations was associated with reduced local Pbro2 and energy metabolism (increased lactate-pyruvate ratio, glutamate and glycerine levels). Elevated serum/plasma and CSF concentrations of VEGF, sFlt-1, and sTie-2 matched the scale of ischemic tissue hypoxia. Excessive VEGF/sFlt-1 and sTie-2 levels were related to Pbro2 values consistently less than 5 mm Hg, glutamate concentrations greater than 300 micromol/L, lactate-pyruvate ratio greater than 300, cerebral infarction, and reduced outcome (P < 0.01). Delayed microcirculatory impairment was mirrored by distinct elevation of cisternal and arterial VEGF and sFlt-1 concentrations, suggesting local induction of angiogenesis. Arterial levels of VEGF, sFlt-1, and sTie-2 reflect both extent and time course of compensatory, yet clinically inefficient, angiogenesis in the absence of general hypoxia.
authors.affiliation: Department of Neurosurgery, University of Freiburg, Germany. scheufle@nz11.ukl.uni-freiburg.de
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Scheufler
authors.forename: Joachim
authors.initials: J
authors.lastname: Drevs
authors.forename: Vera
authors.initials: V
authors.lastname: van Velthoven
authors.forename: Petra
authors.initials: P
authors.lastname: Reusch
authors.forename: Joachim
authors.initials: J
authors.lastname: Klisch
authors.forename: Helmut G
authors.initials: HG
authors.lastname: Augustin
authors.forename: Josef
authors.initials: J
authors.lastname: Zentner
authors.forename: Dieter
authors.initials: D
authors.lastname: Marme
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042787:Receptor, TIE-2; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen