Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker.

BACKGROUND: Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available. METHODS: We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and increased anhedonia evaluated by the sucrose preference test. RESULTS: We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for 28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated these behaviors when induced by chronic immobilization stress. To further test biological differences between both models, we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin. CONCLUSIONS: Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments. Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients.

Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult.

Postmortem biochemical indices may provide a useful adjunct to morphological studies in the identification of antemortem brain insult. We studied 34 routine medico-legal cases categorising them into one of four diagnostic groups. There were 11 cases of head trauma, 7 of 'hypoxia' (3 hangings and 4 carbon monoxide or drug poisonings), 7 sudden cardiac deaths and 9 miscellaneous cases. Survival time and postmortem interval was known for each case. The degree of cranio-cerebral trauma was graded. Cerebro-spinal fluid (CSF) and vitreous humour were analysed for calcium, glucose, total proteins, aldolase, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase BB isoenzyme (CK-BB). CK-BB was also measured in superior vena cava serum. In CSF there was a significant correlation between the severity of cranio-cerebral trauma and levels of aldolase, CK-BB, AST, ALT and total proteins. CSF CK-BB, median units/l (range), for the groupings of head trauma, hypoxia, sudden cardiac death and miscellaneous were respectively 823 (2-3431); 96 (2-187); 4 (2-25); 5 (1-69). Corresponding serum CK-BB levels were 240 (28-322); 390 (26-411); 180 (20-482); 79 (18-530).

[Cerebrospinal fluid level of aldolase C in patients with various neurological disorders: comparison with neuron-specific enolase, S-100b protein and creatine kinase BB isoenzyme].

By employing a highly sensitive immunoassay method, concentration of aldolase C (Ald C) was determined in cerebrospinal fluid (CSF) of 180 patients with various neurological disorders and 46 age-and-sex matched control subjects. The results were compared with CSF levels of neuron-specific enolase (NSE), S-100b proteins (S-100b) and creatine kinase BB isoenzyme (CK-BB) in the same samples. Normal level of Ald C was 7.95 +/- 2.52 (mean +/- SD) ng/ml. CSF level of Ald C was elevated not only in patients with acute disorders, but also those of degenerative diseases. It increased significantly in purulent meningitis, encephalitis, cerebral infarction, and cervical spondylosis as compared with control subjects. The levels of Ald C were reached the peak levels later than those of NSE, S-100b and CK-BB. Concentration of Ald C in CSF correlated well with that of NSE but poorly with that of S-100b or CK-BB. These results suggested that Ald C in CSF was one of the useful marker in neurological disorders. Since these proteins have different distributions in the central nervous system and have different molecular weights, simultaneous determination of Ald C, NSE, S-100b and CK-BB levels in CSF might provide valuable information about pathologic nature of the underlying neurological disorders.

Cerebrospinal fluid aldolase, lactate and creatine phosphokinase in the differential diagnosis of meningitis and meningo-encephalitis.

Creatine phosphokinase, aldolase and lactate determinations were performed on serum and cerebrospinal fluid to assess their value in the diagnosis of tuberculous and purulent meningitis and meningo-encephalitis. Changes in serum were independent of those in the cerebrospinal fluid. Variable results for cerebrospinal fluid creatine phosphokinase were obtained in the three groups. Lactate concentrations in the cerebrospinal fluid showed a clear distinction between tuberculous meningitis and meningo-encephalitis with levels 5 mmol/1 highly suggesting tuberculous meningitis. Also elevated cerebrospinal fluid aldolase levels may exclude meningo-encephalitis as a likely diagnosis.

Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change.

The activities of enolase, aldolase, pyruvate kinase, lactate dehydrogenase and creatine phosphokinase were measured in cerebrospinal fluid of 121 patients presenting with a range of disorders of the central nervous system. The results from 41 patients undergoing myelography were used as controls. An assessment was made of the relative merits of these five enzymes as markers of brain damage with special reference to brain tumours. Enolase was the most sensitive marker of pathological change and was the only enzyme raised in the CSF of patients with low grade astrocytomas.

Investigations on enzyme activity in the serum and CSF of patients with neuromuscular diseases.

The CPK, aldolase, GOT, GPT, and LDH concentrations in the serum and lumbar CSF of 80 patients with neuromuscular diseases and 20 controls were measured. The value obtained in serum was essentially in agreement with the data in the literature. This is the first publications reporting on regular CSF enzyme examinations in different neuromuscular disorders, particularly the results obtained in neurogenic muscular atrophies, which have certain characteristic features. The LDH activity in CSF was decreased in peroneal muscular atrophy, the GPT concentration in CSF was elevated in spinal muscular atrophy, and the mean activity of CSF aldolase was increased in amyotrophic lateral sclerosis. The simultaneous determination of enzymes in serum and CSF can provide valuable information in the research of certain details of pathomechanisms and thus lead to further improvement of diagnosis.

[Etiology and pathogenesis of epilepsy in children]. / K voprosu ob étiologii i patogeneze épilepsii u detei.

Under examination there were 420 children suffering from epilepsy. In 230 of them the convulsive seizures appeared during the first year of the life: in most of these children (71%) this was in the presence of perinatal pathology. A genealogical analysis of 112 families, from which 135 epileptic children descended, is presented. Various types of hereditary epilepsy were revealed. An examination of some enzymes contained in the cerebrospinal fluid of the epileptic patients revealed shifts in their metabolism in cases of both hereditary and sporadic epilepsy. This reflects common features of the pathogenesis of those forms.

Immunoreactive aldolase C in cerebrospinal fluid of patients with neurological disorders.

Nervous-system specific aldolase C has been detected in human cerebrospinal fluid (CSF) by radioimmunoassay. Measurement of 138 samples of CSF showed a mean level of 92 +/- 28 ng/ml. There was no correlation between the level of CSF aldolase C and the CSF total protein, albumin, IgG, or IgA levels. Aldolase C immunoreactivity present in concentrated CSF diluted out in parallel with the standard curve in the assay and showed an elution profile on ion-exchange and gel filtration chromatography similar to that of aldolase present in whole human brain extracts. Addition of known quantities of purified aldolase C4 to CSF gave quantitative recovery on subsequent radioimmunoassay. Measurement of aldolase C in the CSF of 66 patients with neurological disorders showed several patients with levels considerably in excess of 120 ng/ml, but there was no statistically significant difference in the mean levels between groups of patients with different diseases.

Biochemical markers of central nervous system tumors measured in cerebrospinal fluid and their potential use in diagnosis and patient management: a review.

The concept of tumor markers was reviewed, and the potential uses of markers of central nervous system (CNS) tumors and methods for their evaluation were discussed. Markers examined included lactate dehydrogenase, aspartate aminotransferase, fructose-bisphosphate aldolase, the polyamines, desmosterol, and several other enzymatic, nonenzymatic, and immunologic markers. Data collated from the clinical studies surveyed showed isocitrate dehydrogenase, desmosterol, and the polyamines to have the greatest potential utility in the diagnosis of CNS tumors.

Cerebrospinal fluid fructose-biphosphate aldolase (aldolase) activity in infectious diseases of the central nervous system.

Aldolase levels were estimated in the cerebrospinal fluid of patients with infectious diseases of the central nervous system. A significant rise was found in bacterial and cryptococcal meningitis but the investigation failed to elucidate the source and clinical significance of the elevated activity.

Changes in serum and cerebrospinal fluid enzyme activity after head injury.

We studied simultaneously in serum (S) and CSF (L) the enzyme activities of GOT, GPT, LDH, ICDH, MDH, ALD, and CPK in 28 patients with head injuries divided into three groups according to the severity of the trauma. We found a correlation between severity of brain lesion and enzyme activity. The best correlation was found for SGOT, SCPK, LGOT, LLDH, LMDH and LCPK. We do not believe that enzyme activity is of prognostic value. We think that further studies should be made of the specific isoenzymes of the Central Nervous System.

The present status of prenatal detection of neural tube defects.

In experimentally induced myelocele in rats, efforts to find neural cells in amniotic fluid (AF) were unsuccessful. Creatine phosphokinase (CPK) and aldolase concentrations studied in serum of 118 and cerebrospinal fluid (CSF) in 9 patients with myelomeningocele showed serum CPK to be significantly elevated and more responsive to additional muscle injury than aldolase, but both enzymes appeared in lower concentrations in patients with myelomeningocele than those with infantile atrophy or cerebral palsy. In CSF, CPK, and aldolase concentrations averaged 4.2 I.U. and 2.7 S.L.U. per milliliter, respectively. Significant CPK elevation (p less than 0.001) was also found in AF from myeloschitic fetuses and maternal rat serum. Although these findings suggest that increased CPK concentration is an indicator of myelocele in rats, the technique is impractical for prenatal detection of human fetus occurs too late in gestation. This does not, however, preclude the value of CPK for detecting onset of paraparesis. In all myeloschitic human fetuses, the CSF communicates directly with AF for at least 3 to 4 weeks. This implies that CSF is probably the principal source of increased alpha-fetoprotein concentration encountered in AF of all pregnancies with NTD. When biological variables are recognized, it is evident that increased concentration of amniotic fluid alpha fetoprotein is a reliable indicator of fetuses with open myelocele and/or anenciphalus.