Brain-type creatine kinase isoenzyme. Occurrence in serum in acute cerebral disorders.

Acute brain damage-cerebrovascular or cardiovascular, traumatic or infectious-released brain-type isoenzyme of creatine kinase (BB-CK) into the circulation within a few hours in 16 of 62 patients (26%). Occurrence of BB-CK was transient in the serum. BB-CK activity was found in the peripheral blood in 13 of 23 patients with diffuse brain damage compared to three of 39 patients with a local cerebrovascular accident (P less than .0005). The mortality of patients having BB-CK in their serum was 63% compared to 39% of those without BB-CK activity in their serum (P less than .05).

Increased therapeutic efficacy with rt-PA and anti-CD18 antibody treatment of stroke in the rat.

OBJECTIVE: To examine the efficacy of an antileukocyte adhesion antibody (anti-CD18) as an adjuvant for delayed (2 hours and 4 hours) thrombolytic therapy (recombinant human tissue plasminogen activator [rt-PA]) in middle cerebral artery occlusion (MCAO) in rats. BACKGROUND: Thrombolytic therapy with rt-PA is limited in its application by a short therapeutic window. METHODS: Male Wistar rats were subjected to MCAO by a single fibrin-rich clot. The rats were assigned to the following experimental groups: Experiment 1 (treatment 2 hours after embolization), 1) rt-PA, 2) anti-CD18 antibody, 3) rt-PA and anti-CD18 antibody, 4) immunoglobulin (Ig) G, and 5) vehicle; Experiment 2 (treatment 4 hours after occlusion), 1) rt-PA alone, 2) rt-PA and anti-CD18 antibody, and 3) nontreated control group. Neurologic deficits, infarction volume, hemorrhage, and brain myeloperoxidase (MPO) immunoreactivity were measured. RESULTS: Administration of rt-PA and anti-CD18 antibody 2 hours later reduced significantly (p < 0.05) the infarct volume and improved neurologic deficits compared with the vehicle-treated group. Treatment with rt-PA alone improved neurologic deficits significantly and reduced mean infarct volume compared with the vehicle-treated group. However, treatment with anti-CD18 antibody neither reduced infarct volume nor improved neurologic deficits compared with the IgG-treated group. The combination of rt-PA and anti-CD18 antibody treatment at 4 hours reduced significantly the infarct volume and MPO immunoreactive cells compared with rt-PA treatment alone at 4 hours, and reduced neurologic deficits compared with rt-PA treatment alone and compared with the nontreated animals. CONCLUSIONS: The combination of antileukocyte adhesion antibody and thrombolytic therapy may increase the therapeutic window for the treatment of stroke.

Cerebral embolization impairs memory function and reduces cholinergic marker enzyme activities in various brain regions in rats.

Cerebral embolization was produced by injecting microspheres into the left internal carotid artery in rats. In these embolized rats, passive avoidance response was impaired at early stages after the embolization (3 days, 1 and 2 weeks), but 4 to 8 weeks later, recovery was achieved. A reduction in the activities of choline acetyltransferase (CAT) in the left side of the occipital cortex and hippocampus was observed in parallel with the impairment of learning behavior. These results suggest that impairments in the septo-hippocampal cholinergic pathways are likely to be closely related with the behavioral impairment in these rats.

Evaluation of enzymes in serum and cerebrospinal fluid in cases of cerebrovascular accidents.

Gamma glutamyl transpeptidase (GGTP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were measured serially in the serum and cerebrospinal fluid (CSF) of 22 patients with fresh stroke and an equal number of age- and sex-matched healthy control subjects. It was observed that levels of these enzymes in the CSF of control subjects were very low but were significantly elevated (p less than 0.001) in both serum and CSF in patients with stroke. The elevation was greater in the CSF than in the serum and was maximum during the first four days of stroke. Thereafter, the enzymatic activity declined. Of all these enzymes, GGTP in CSF correlated best with the clinical picture. It was possible to differentiate between the ischemic and hemorrhagic type of stroke on the basis of CSF levels of GGTP (greater than 60.0 units in hemorrhagic stroke). There was no correlation between GGTP levels in CSF and serum or among GOT, GPT, and GGTP in CSF. It can be concluded, therefore, that estimation of GGTP in CSF is helpful not only in predicting the degree of cerebral damage and functional outcome of the patient following stroke but also in differentiating the type of stroke.

Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism.

Plasma activity of myeloperoxidase (MPO), malondialdehyde (MDA) and 4-hydroxynonenal (HNE) was measured prior to any treatment in 50 consecutive stroke patients with acute cerebral ischaemia, as well as in 14 healthy control subjects. Mann-Whitney-Wilcoxon test for unpaired data showed greater values of MPO (p < 0.01), MDA (p < 0.01) and HNE (p < 0.05) in stroke patients compared with controls. Considering as covariates the level of consciousness (GCS < 9 vs > or = 9), possible sources of emboli (yes vs no), leukocyte count (< 10 x 10(9)/1 vs > or = 10 x 10(9)/1) and relevant comorbid diseases (yes vs no), exact multiple logistic regression analysis indicated that only the presence of possible cardiac sources of emboli was associated with changes in by-products of lipid peroxidation. If confirmed in a larger series of subjects, our results could have therapeutic implications, providing more support for the use of free radical scavengers in the acute care of stroke patients with a possible cardioembolic aetiology.

[Phosphocreatine kinase activity in the cerebrospinal fluid in different types of stroke]. / Aktywnosc kinazy fosfokreatynowej (CPK) w plynie mózgowo-rdzeniowym w róznych rodzajach udarów mózgowych.

In 45 patients with brain strokes (thrombosis, embolus, intracerebral haemorrhages) and subarachnoid haemorrhages the CPK activity was determined in the cerebrospinal fluid. In most cases a significant rise was observed in CPK activity in the cerebrospinal fluid as compared to the control group. In two cases the dynamics of CPK activity changes were studied in the cerebrospinal fluid during the stroke. It seems that a significant rise in CPK activity develops in the initial phase of the stroke when the area of nervous tissue softening develops and spreads.

[Myeloperoxidase activity as an indicator of leukocyte infiltration into the ischemic area in the middle cerebral artery occlusion model of the rats].

Myeloperoxidase was solubilized with hexadecyltrimethylammonium bromide and myeloperoxidase activity was measured with a dianisidine-H2O2 assay in the ischemic area after middle cerebral artery occlusion in rats. This enzyme could be measured 6 hours after the occlusion of the middle cerebral artery, then showed two peaks, one after 8 hours and another after 18 to 24 hours in 2 phase fashion as could be measured as far as 7 days, which was the termination of this experiments. These findings suggest that leukocyte infiltration into the ischemic area play an important role for the extension of the ischemic area. Further study should undertake whether leukocyte depletion decrease the ischemic area or not.

[Alkaline phosphatase and ATPase activity in the walls of the cerebral vessels in hypertension and arteriosclerosis with disorders of the cerebral circulation]. / Aktivnost' shchelochnoi fosfatazy i ATF-azy v stenkakh sosukov golovnogo mozga pri gipertonicheskoi bolezni i ateroskleroze s narusheniiami mozgovogo krovoobrashcheniia.

In hypertensive disease and atherosclerosis without acute disorders of cerebral circulation it was established that in the cerebral vessel walls there was a high activity of alkaline phosphatase and adenosintriphosphtase. In the symmetrical areas of the subcortical nodes differences in the activity of these enzymes were insignificant and not valid. In vessel walls, located in the peripheral zone of the apoplectic hemorrhage and in the adjacent brain tissue the activity of alkaline phosphatase and adenosintriphosphatase drops. The existence of a high activity of enzymes in the vessel walls on the early stages of hemorrhages gives ground to the authors to claim that in the peripheral zone of an extensive hemorrhage a drop in the enzyme activity appears in the process of a development of a stroke.

Platelet-activating factor acetylhydrolase activity in red blood cell-stroma from patients with cerebral thrombosis.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) is a bioactive phospholipid and inactivated by a specific enzyme, PAF acetylhydrolase (PAF-AH). We have measured PAF-AH activity in red blood cells (RBCs) from patients with a history of cerebral thrombosis and age-matched healthy controls. The activities in 34 patients and 34 controls were 1.29 +/- 0.28 and 1.64 +/- 0.26 nmol/10(9) RBCs/min (or, 30.0 +/- 5.8 and 35.1 +/- 4.7 nmol/g protein/min) (mean +/- SD), respectively, and the difference was significant (p less than 0.001). In patients, RBC PAF-AH activity correlated positively with RBC filterability, an index of RBC deformability (r = +0.501, p less than 0.05). The RBC activity may play a role in scavenging oxidation products of membrane phospholipids. Lower RBC PAF-AH activity may predispose to ischemic diseases by disturbing microcirculatory behavior of the RBCs.

Nitrous oxide and cerebrospinal fluid markers of ischaemia following cardiopulmonary bypass.

Twenty patients with good ventricular function undergoing coronary artery bypass surgery were studied to determine whether the pre-bypass use of nitrous oxide resulted in any differences in cerebrospinal fluid markers indicative of cerebral ischaemia. All patients were anaesthetised with diazepam, fentanyl and pancuronium, after which ten patients received 50-60% nitrous oxide in oxygen until commencement of bypass, and the remaining patients 100% oxygen. Because of the known effect of nitrous oxide in expanding gaseous bubbles, any neurological dysfunction of gaseous microembolic origin may be worsened in the presence of nitrous oxide. Patients were lumbar punctured 24 hours after cardiopulmonary bypass and cerebrospinal fluid analysed for the following markers of central nervous system ischaemia: creatine kinase, lactate, total protein, noradrenaline, adrenaline and adenylate kinase. There was a statistically significant difference in cerebrospinal fluid lactate between the two groups. There were no statistically significant differences in the other cerebrospinal fluid markers of ischaemia.

Assessment of cerebral damage during open-heart surgery. A new experimental model.

A new experimental technique for the assessment of cerebral cellular damage during extracorporeal circulation is described. It is based upon the direct measurement of the enzyme creatine phosphokinase (CPK) and the brain-specific isoenzyme CPK-B in cerebrospinal fluid of dogs submitted to conventional techniques of cardiopulmonary bypass (CPB). Highly significant elevations occur during a 60 min period of CPB in CSF levels of total CPK and CPK-B isoenzyme. These elevated levels persist at 24 hours postoperation, despite full clinical recovery in the dogs. In a comparative study of the effects of introducing a 40 micrometer arterial line screen filter during the period of CPB, there was a highly significant reduction in total CPK and CPK-B levels in the filtered group (p < 0.005).

[Cerebrospinal fluid (CSF) cytochemistry of acute cerebrovascular diseases with clear CSF: observation of nonspecific esterase activity of mononuclear phagocytes].

CSF nonspecific esterase (ANAE) activities of mononuclear phagocytes of 35 patients with intracerebral hematoma (ICH) with clear CSF and 25 with cerebral thrombosis and 17 normals were observed. The ANAE activities of ICH were much higher than those of thrombosis significantly (P less than 0.01). Furthermore, the distributions of ANAE activities of all cases suggested that there were few overlaps between both diseases. The CSF cytochemical detection was obviously superior to routine CSF cytological examination in differentiating strokes with clear CSF. The authors concluded that these results provided a simple inexpensive and relatively accurate method to differentiate hemorrhagic from ischemic cerebrovascular diseases in case of without CT.

Plasma 11-dehydrothromboxane B2: a reliable indicator of platelet hyperfunction in patients with ischemic stroke.

The plasma level of 11-dehydrothromboxane B2 (11-dehydroTXB2) is free from artifactual increase during blood sampling, and it can be reliable indicator of TXA2 production in vivo. We have estimated plasma 11-dehydroTXB2 in patients with ischemic stroke. Subjects studied were 29 patients with cerebral thrombosis (62 +/- 9 years old) and 41 healthy controls (61 +/- 7 years old). Plasma 11-dehydroTXB2 and TXB2 were determined by radioimmunoassay. Plasma 11-dehydroTXB2 levels in patients and controls were 5.4 +/- 2.5 and 1.8 +/- 0.9 pg ml, respectively, and the difference was significant (p less than 0.001). Plasma TXB2 also was higher in patients than in controls: 401 +/- 61 vs 311 +/- 51 pg/ml (p less than 0.05). However, the 11-dehydroTXB2 was found to be a more effective parameter to distinguish between stroke patients and controls. Estimation of plasma 11-dehydroTXB2 levels is a reliable method to detect platelet hyperfunction in stroke patients.

Plasma semicarbazide-sensitive amine oxidase in stroke.

Semicarbazide-sensitive amine oxidase (SSAO) has been suggested to be involved in the development of vascular endothelial damage. The source of the soluble form of SSAO found in the blood serum is unknown. However, it has been speculated that it is secreted from cells within the vascular wall where high activity of the enzyme is found. Altered SSAO activity has been reported in atherosclerotic plaques of the human aorta. Stroke is a manifestation of long-term atherosclerotic disease, and in this study, plasma SSAO activities were estimated in 42 patients with cerebral thrombosis and 26 patients with cerebral embolism, and compared to two control groups of 45 individuals in total. No statistically significant differences were found between the patient groups and controls regarding plasma SSAO activity, suggesting that changes in the soluble form of SSAO found in the circulation do not play a major role in this type of acute cerebrovascular event. Furthermore, it does not seem likely that the involvement of vascular tissue occurring in stroke results in release of the enzyme into the circulation. Nevertheless, further studies on tissue-bound SSAO in cerebral vessels would be of great interest.

Evaluation of serum lipid profile and cardiac enzyme changes in cerebrovascular accidents.

Serum lipid profile is, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides and serum cardiac enzymes ie, creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme MB (CPK-MB), lactate dehydrogenase (LDH) and serum aspartate aminotransferase (AST/SGOT) levels were estimated in 50 cases of cerebrovascular accidents (CVA) consisting of 26 cases of cerebral haemorrhage and 24 cases of cerebral thrombosis. All analyses were made on day 1 and day 7. Serum cholesterol, LDL and triglycerides levels were significantly higher in CVA patients on day 1. Lipid level fell significantly on day 7 in respect to day 1. On comparing the lipid levels between cerebral haemorrhage and cerebral thrombosis, no significant difference was observed. Cardiac enzymes like CPK and CPK-MB were significantly raised whereas, AST/SGOT and LDH were marginally raised on day 1 in CVA patients. However, there was no change in cardiac enzyme levels between cerebral haemorrhage and cerebral thrombosis patients.