Serum Markers of Apoptosis in Traumatic and Ischemic Brain Injury

Abstract

Objective: to study the time course of changes and relationship of the serum indicators of apoptotic processes in neurore-suscitation patients. Subjects and methods. Thirty-eight neuroresuscitation patients, including 14 patients with severe brain injury (SBI) (mean age 41.4±4.3 years) and 24 patients with strokes (mean age 53.8±2.5 years), were examined. The group of patients with strokes was divided into 2 subroups: 1) 11 patients with ischemic strokes (IS) and 2) 13 with hemorrhagic strokes (HS). The Glasgow coma scores for admission consciousness loss were 7.6±0.8 in the SBI group and 9.5±0.7 in the stroke group; mortality was 28.6 and 37.5%, respectively. A control group included 16 subjects (mean age 47.9±3.8 years). The investigators measured the serum levels of FAS antigen and its ligand (sAPO-I/FAS and sFAS-L), cas-pase-1/ICE, sCD40 (Bender MedSystem, Austria) and hTRAIL (Biosource, Belgium) by solid-phase immunoassay in neuroresuscitation patients on days 1, 7, and 14 of the acute period of diseases. They used statistical methods, such as Wilcoxon-Mann-Whitney U-test, Spearman’s rank correlation test. Results. A reduction in hTRAIL was observed in all the groups. There was a decrease in serum sCD40 in strokes on days 1 to 14 and in SBI on days 7 to 14. An increase in caspase 1/ICE was seen in HS in the first 24 hours, in IS on days 1 to 7, and in SBI on days 1 to 14. The most pronounced rise in caspase-1/ICE was induced by ischemic brain lesion within the first week of disease. A prolonged increase up to 2 weeks was noted in SBI. No rise in serum FAS-L was found in the examinees. The time course of changes in sAPO-I/FAS was different in all the groups. The most marked, moderate, and none reductions were revealed in HS, IS, and SBI, respectively. There was a pronounced serum sAPO-I/FAS increase in SBI within the first 24 hours. Assessment of correlations between the serum indicators of apoptosis revealed that there were differences in the association between the indices under study in all the patient groups and in the control group. Conclusion. There are general features and differences in the time course of changes in serum apoptotic markers and their association in the acute period of SBI, IS, and HS. Key words: severe brain injury, stroke, apoptosis, APO-I/FAS, FAS-L, caspase-1/ICE, CD40, hTRAIL.