Our preliminary results indicate that SAH leads to an increase in NO-M in CSF. This increase of NO-M significantly correlates with the flow velocities in TCDS measurement suggesting that NO plays an important role in the pathogenesis of cerebral vasospasm.

Mean ICP even before brain death determination is increased excessively. Changes of ICP during apnoea show a clear correlation to the changes of MAP. Furthermore, CPP during the condition of brain death may not equal zero but may be positive thereby indicating some minor net influx of blood into the brain in some patients.

The hypothesis was tested in rats that brain ischemia by an intracerebral hematoma can be ameliorated by fibrinolysis and aspiration of the hematoma. Intraparenchymal blood clots were generated by the injection of 50 microliters of autologous blood into the right caudate nucleus in two portions seven minutes apart. Thirty or 120 min later 12 microliters recombinant tissue plasminogen activator (rtPA) or 0.9% NaCl were injected and after 30 min the resolved hematoma was aspirated. Six hours later cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography. Tissue volumes of CBF < 10 ml 100 g-1 min-1 and CBF < 30 ml g-1 min-1 were determined. Clot and lesion volume were quantified histologically from serial sections stained for succinate-dehydrogenase (SDH) activity. In rtPA-treated rats the major part of the hematoma could be evacuated 30 min as well as 120 min after production of the clot. The volume of ischemic brain (CBF < 10) was significantly reduced (p < 0.05) in the rtPA group compared to saline-treated and control groups irrespective of the time of treatment. In contrast, no difference was found between the control group and the experimental groups when the volumes of brain tissue surrounding the lesion were compared which had values of CBF < 30 ml 100 g-1 min-1. In a rat model of intracerebral hemorrhage, treatment by local fibrinolysis followed by aspiration of the hematoma is effective in reducing the volume of ischemic brain tissue and of the remaining clot volume.

In 12 operatively (stereotactic aspiration and recombinant tissue-type plasminogen activator, rTPA) and 5 conservatively treated patients with spontaneous intracerebral hemorrhage the amounts of cysteinyl-leukotriene (cys-LT) released by blood-brain cell contact were measured by the urinary excretion of their metabolites during treatment. The mean cys-LT release before treatment was 14.51 ± 1.13 pg/mg creatinine/ml hematoma volume. The urinary cys-LT excretion at the end of the measurements was significantly lower in the operatively treated group than in the patients with conservative therapy (p < 0.05). We also found a significant correlation between the perifocal edema volume and the amount of cys-LT measured in patients’ urine (p < 0.01). In an additional animal experiment using dissociated rat brain cells plasmin was excluded as an activator for cerebral cys-LT formation, which emphasizes that rTPA did not influence cys-LT formation.

Accidental and operative trauma are able to induce a systemic reaction of the organism characterized by fever, leukocytosis, catabolism, and an activation of the coagulation system. Interleukin-6 (IL-6) has been found to be an important mediator of this acute-phase response. In this study the influence of elective craniotomy on IL-6 plasma levels was evaluated. Blood samples were obtained from 20 patients undergoing elective craniotomy for vascular or tumorous diseases of the brain. IL-6 increased significantly (p < 0.05) from the pre-operative (0(0-5.4) pg/ml) to the intraoperative (180 min after beginning of surgery) time-point (10.6 (0-18.5) pg/ml). The maximum was reached on the first postoperative morning (13.9(4.3-45.0) pg/ml). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which suppresses IL-6 synthesis in vitro in various cell lines. IL-10 plasma concentrations showed no alterations throughout the study period. Epinephrine plasma concentrations increased significantly from pre-operative values (15 (0-74) pg/ml) to the postoperative time-point (57(9-459) pg/ml). A 4.5-fold increase (p < 0.05) of norepinephrine plasma concentrations was found when comparing the data obtained 60 min after beginning of surgery with the data of the first postoperative morning. In monocytes, which are a major source of plasma IL-6, an elevation of intracellular cAMP stimulates the IL-6 synthesis. The postoperative maximum of IL-6 in plasma could be due to a release of catecholamines. In conclusion this study demonstrated an elevation of IL-6 plasma concentrations during and after elective craniotomy. Increased plasma catecholamine concentrations as well as a damage in the blood-brain barrier due to the surgical trauma with a spill-over of IL-6 from brain tissue into plasma could have contributed to this result.