Despite advances in surgical treatment and postoperative care, subarachnoid hemorrhage from ruptured cerebral aneurysms remains a devastating event. Excellent surgical results in treating unruptured aneurysms suggest the utility of screening tests to identify high-risk individuals. Unfortunately, none of the known risk factors for subarachnoid hemorrhage correlates strongly enough with the illness to warrant widespread screening for occult aneurysms. Other disease entities suggest that protease-antiprotease imbalances contribute to somatic vessel wall degradation and aneurysm formation. Detection of similar imbalances in selected patients may identify a predisposition to cerebral aneurysm formation. Serum concentrations of elastase and alpha-1-antitrypsin (AAT), important proteolytic and antiproteolytic enzymes, were measured in a series of 19 patients with unruptured aneurysms, 41 patients with ruptured aneurysms, and 27 age-matched operative and nonoperative controls. The elastase:AAT ratio was nearly twice as high in patients with unruptured aneurysms as in operative controls (0.527 +/- 0.1 versus 0.285 +/- 0.06; P < 0.04). Elastase:AAT ratios in patients with ruptured aneurysms (subarachnoid hemorrhage < 48 h) were roughly twice those of controls (0.582 +/- 0.095; P < 0.01). There was no statistical difference between elastase:AAT ratios for patients with ruptured and unruptured aneurysms. Likewise, elastase-AAT values for operative controls and nonoperative volunteers were not significantly different. Differences in serum elastase:AAT ratios between patients with aneurysms and controls reflected differences in elastase concentration (99 +/- 56 micrograms/ml versus 67 +/- 56 micrograms/ml; P < 0.03), not in AAT levels (147 +/- 56 micrograms/ml versus 141 +/- 56 micrograms/ml; P < 0.72).(ABSTRACT TRUNCATED AT 250 WORDS)

Although the cerebroprotective effects of hypothermia in focal models of ischemia are undisputed, the underlying mechanisms of this protection are still subject to much controversy. To analyze whether mild hypothermia attenuates glutamate levels in the penumbra surrounding permanent focal infarcts, extracellular glutamate concentration was analyzed bilaterally by microdialysis 20 minutes before to 120 minutes after a middle cerebral artery occlusion (MCAO) in rats. Normothermic animals (n = 11) had a baseline glutamate concentration of 1.14 +/- 0.40 mumol/ml (standard error of the mean) before the MCAO. Extracellular glutamate levels increased gradually after vessel occlusion to peak at 10.1 +/- 1.45 mumol/ml 80 minutes after the MCAO. This level gradually decreased to 5.72 +/- 1.67 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had a baseline glutamate concentration of 1.73 +/- 0.83 mumol/ml before the MCAO. Extracellular glutamate levels increased after vessel occlusion but stabilized at 3.47 +/- 1.37 mumol/ml 30 minutes after the MCAO and remained stable until completion of the experiment. There were no significant differences in cortical blood flow between the normothermic and hypothermic groups at any time during the experiment. Infarct volumes, expressed as a percentage of the volume of the right (ipsilateral) hemisphere, were 19.8 +/- 2.16% in the normothermic group and 13.0 +/- 1.42% in the hypothermic group (P < 0.02). Although the normothermic penumbral glutamate levels began to increase immediately after the MCAO, they did not peak until 80 minutes after occlusion. In contrast, the normothermic core glutamate levels peaked within 30 minutes after the MCAO. Glutamate diffusion from the core region to the penumbra might account for this delay. Hypothermic cerebroprotection might involve a reduction in the pool of potentially diffusable glutamate in the core region but have little direct effect on glutamate release in the penumbra.