[Leukotriene synthesis after intracerebral hemorrhage: a further indicator for their pathophysiologic significance in the CNS].
Blood brain cell contact activates lipid peroxidation and arachidonic acid metabolism as shown in animal experiments. Previous studies in tumor patients have shown that enhanced cysteinyl-leukotriene (cys-LT) formation leads to increasing perifocal edema. This suggests their involvement in CNS pathology. The purpose of this study is to measure the amounts of cys-LT released during blood-brain cell contact in patients with spontaneous intracerebral hemorrhage (ICH). Seventeen patients were divided into two groups. One of them was treated conservatively, the other group received a local rTPA therapy after stereotactic puncture and hematoma reduction by aspiration. Before treatment as well as during the following 5 days cerebral cys-LT release was measured analyzing the metabolites in patients urine. The mean cys-LT release before treatment ranged at 14.51 +/- 1.13 pg/mg creatinine/ml hematoma volume. In the conservative treatment group urinary cys-LT release dropped to 14.05 +/- 1.1 pg/mg creatinine/ml hematoma volume by the fifth day of treatment. The change of urinary cys-LT release in the operatively treated patients was much more distinct: Five days after rTPA therapy urinary cys-LT release was 11.23 +/- 0.6 pg/mg creatinine/ml tumor volume. The urinary cys-LT excretion at the end of the measurement was significantly lower in the operatively treated group (p < 0.05). In an additional experimental approach using dissociated rat brain cells plasmin was excluded as an activator for cerebral cys-LT formation. Variation in incubation time as well as the concentration of plasmin exhibited no difference in cys-LT release in comparison to the incubation of dissociated rat brain cells without any external stimulus. These results emphasize that rTPA does not influence cys-LT formation in a direct way. After experimental evidence, these results indicate now in a clinical evaluation that cerebral cys-LT formation is activated during blood-brain cell contact also in patients suffering from intracerebral hemorrhage. The amounts of cys-LT release depend on hematoma volume. Hematoma reduction by aspiration and rTPA treatment is followed by a distinct reduction of cys-LT release.
Winking
M
M
Neurochirurgische Klinik, Justus-Liebig Universität Giessen.
Deinsberger
W
W
Jödicke
A
A
Böker
D K
DK
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D003545:Cysteine / Q000502:physiology*; D005260:Female; D006801:Humans; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D010959:Tissue Plasminogen Activator; D003545:Cysteine