Monitoring of extracellular substances after spontaneous and experimental subarachnoid hemorrhage

Abstract

Even though survival is considerably enhanced after surgical treatment of an aneurysmal subarachnoid hemorrhage (SAH), there is a critical period, which keeps the patient in intensive care for days or even weeks. Complications, such as vasospasm, ischemia and brain edema ultimately lead to further brain damage.The introduction of microdialysis allows regional monitoring of the cerebral extracellular fluid (ECF) for levels of metabolites and marker substances, which may predict development of various complications. However, the results are often difficult to interpret due to the heterogeneity of the patient groups. This thesis addresses the question of whether it is possible to follow courses of events after SAH by monitoring the cerebral ECF with respect to molecules of prognostic value. A model was developed for SAH (I), which compares the effects of blood and of increased ICP. The deleterious effects were mainly ascribed to blood in the subarachnoid fluid.Traumatic SAH (tSAH) is the most common type and is similar to spontaneous SAH with respect to secondary effects, such as vasospasm. Rotational acceleration of the head provides extensive tSAH (II). Glutamate and glycine increased in the hippocampal ECF in agreement with (I), but in addition, the trauma caused increased taurine and GABA. In contrast, aspartate, alanine and serine were less affected than after spontaneous SAH. Extensive neuronal loss occured in the tSAH model, both in the cerebral cortex, hippocampus and cerebellum, an effect interpreted to have a causal relationship with the high concentrations of excitatory amino acids in the ECF. A disadvantage of the tSAH model was the difficulty to distinguish effects of the hemorrhage and of the trauma per se.Seizures, caused by exposition of brain tissue to extravascular blood for a prolonged time, are common after SAH. Breakdown products of hemoglobin have been proposed as causes, paticularly after repeated bleedings. An obvious model for this question are cavernous angiomas (CA), a form of vascular malformations. The main symptoms are seizures, which often disappear upon the excision of the CA. Excised CAs from 10 patients were characterized biochemically (III). Iron and GFAP were markedly elevated in the angiomas as well as in the surrounding gliotic tissue. In the gliotic tissue, the concentrations of glycine and glutamine were increased, but that of GABA decreased.In two clinical studies with microdialysis sampling, SAH patients were operated with clip ligatures of ruptured arterial intracranial aneurysms. Neurotransmitter amino acids and other amino acids, as well as the glial marker protein GFAP were analyzed. The level of total amino acids in the ECF appeared to be higher in patients with low levels of consciousness (IV). Transient elevations of taurine and also of glycine and serine were more frequent than increases of the excitatory amino acids glutamate and aspartate (IV). The concentration of GFAP was higher in the ECF close to the site of the ruptured aneurysm. Specific changes in the concentrations of GFAP also coincided with events such as increased intracranial pressure (ICP), vasospasm and ischemia.