@article{SirenHeldmanDoronetal.1992,
  author    = {Sir{\´e}n, Anna-Leena and Heldman, Eliahu and Doron, David and Yue, Tian-Li and Liu, Yong and Feuerstein, G. and Hallenbeck, JM},
  title     = {Release of proinflammatory and prothrombbtic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47469},
  year      = {1992},
  abstract  = {Background and Purpose: We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of Iipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats. MethotJs: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1a, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after achallenge with Iipopolysaccharide. Results: Little or no activity from these media tors was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of Iipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not c1early dose-related. When Iipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not aItered significantly between the two rat strains. Conclusions: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection oflipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.},
  subject      = {Gehirn},
  language  = {en}
}
@article{FrerichsSirenFeuersteinetal.1992,
  author    = {Frerichs, K. and Sir{\`e}n, Anna-Leena and Feuerstein, G. and Hallenbeck, JM},
  title     = {The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47980},
  year      = {1992},
  abstract  = {Background and Purpose: Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypo perfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons. Metho(Js: We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 p,g ibotenic acid in 1 p,1; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sampie volume of the laser Doppler probe (1 mm3 ). Local cerebral blood flow was measured within the injection site and at an adjacent control site. Results: Ischemia was followed by marked hyperemia (235 ±23\% of control, n =7), followed by secondary hypoperfusion (45±3\% of control, n=7). The transition from hyperemia to hypoperfusioo occurred not gradually but precipitously (maximal slope of flow decay: 66±6\%/min; n=7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5±3\%/min compared with 53±8\%/min at the control site; n=5, p<O.OOI) and 00 significant hypoperfusion de\eloped (103±20\% of control at 60 minutes). Conclusions: These data suggest that the rapid transition to cortical hypo perfusion after forebrain ischemia may be triggered locally by a neuronal mechanism but that this mechanism does not underlie the initial hyperemia.},
  subject      = {Gehirn},
  language  = {en}
}