Abstracts

Rationale: EPS occur in 5-10% of strokes and have deleterious impact on stroke outcome. The molecular mechanisms of EPS remain obscure. The purpose of the study was to evaluate neurochemical indices in CSF related to nitrergic system and major proteases executing neuronal cell death. Methods: Twenty eight acute stroke patients with early poststroke seizures and 25 - without them were investigated. Both groups were similar in age, gender, NIHSS. Among stroke patients with seizures there were 15 patients with carotid territory ishemic stroke and 13 - with hemorrhagic stroke, among stroke patients without seizures - 13 and 12, respectively. Nitric oxide synthase (NOS) activity was assayed by conversion of radiolabeled arginine to citrulline, NOx levels - using a fluorescent probe diaminonaphtalene, proteolytic activities - fluorometrically with substrates for caspase-3, calpain, cathepsin B. Results: A prominent accumulation of NOx in CSF of patients with ischemic stroke was demonstrated during the first 24 hours after the onset of stroke (7.4+/-1.7 vs. 3.0+/-0.6 µmol/l in controls, P=0.02). This phenomenon was evident neither in ischemic stroke patients with EPS (2.5+/-0.5 µmol/l , P=0.01), nor in hemorrhagic stroke, irrespective of EPS (2.1+/-0.4 and 2.0+/-0.4 µmol/l without and with EPS, respectively). The accumulation of NOx did not correlate with the post-stroke appearance of NOS activity in CSF. In controls, NOS activity was negligible, in ischemic stroke patients it was quite low, while in CSF of patients with hemorrhagic stroke a significant NOS activity was detected. Though not statistically significantly, NOS activity tended to increase in CSF of patients with EPS. We suggest that NOS is released into CSF from damaged brain cells or cells penetrating damaged blood-brain barrier. In ishemic stroke patients with and without EPS no difference in cathepsin B-inhibiting CSF activity could be revealed, but the calpain-inhibiting activity was more expressed in EPS patients (45.6+/- 1.9% of residual activity vs. 56.4+/- 2.9%, P<0.05), and caspase-3-activating activity was more significant in patients without EPS (132.5+/- 4.7% vs. 115.5+/- 3.3, P<0.03).