Current status of intrathecal antifibrinolytic therapy with p-aminomethylbenzoic acid (PAMBA) in subarachnoid hemorrhages

The blood-brain barrier is barely affected by slight or moderate subarachnoidal bleeding so that the p-aminomethylbenzoic acid (PAMBA) administered systemically for antifibrinolytic therapy does not attain the continuous level necessary in the cerebrospinal fluid. Thus the antifibrinolytic agent should be applied intrathecally because this would totally inhibit fibrinolytic activity in cerebrospinal fluid containing blood and during the wound healing of ruptured aneurysmas. The improvement in wound healing reduces the occurrence of rebleeding, especially during the first 10 days, and improves conditions for successful surgical intervention.     

IgG determination in the cerebrospinal fluid--correlation of these results with other cerebrospinal fluid values

IgG determined by means of quantitative radial immunodiffusion in the cerebrospinal fluid of 225 neurological patients correlates in a statistically significant manner (p less than 0.001) with the gamma-globulin determined by the acetate foil electrophoresis. The indication of the IgG as a percentage of the total protein (limiting value of 10 per cent) is suitable for an orientating assessment in the diagnosis of inflammatory-immunoreactive diseases of the central nervous system. The IgG-values exceeding 10 per cent of the total protein correlate in 260 fluids examined in the respect with the percental value of the lymphocyte content which also lies above the reference range (p less than 0.001). For the assessment of the presence of a barrier disturbance, a comparison with the serum values should be carried out, either in the form of the frequently used fluid/serum quotients of the immunglobulin or the electrophoretically separated protein fraction.     

On central control of body fluid homeostasis

The paper is a discussion of the manners in which cerebral receptor systems may perceive the changes in the internal environment which arise in consequence of deviations from fluid balance. Arguments are presented against the current osmoreceptor theory which implies that receptors in the hypothalamic region are stimulated directly by blood hypertonicity. Recent studies are reviewed which indicate that a possible alternative to hypothalamic osmoreceptors may be receptors in the close vicinity of the third ventricle which are influenced by the Na⁺ concentration of the cerebrospinal fluid. Evidence is presented that a sodium sensitive receptor system of this kind participates, not only in the control of water balance, but also in the regulation of the renal Na⁺ excretion and of the arterial blood pressure. The demonstration of a striking central sodium-angiotensin interaction implies that periventricular sodium sensitive receptors also may be a final link in a volumetric regulation of thirst and ADH release which is mediated by the reninangiotensin system.     

Diagnostic value of alpha 1-acid glycoprotein in the cerebrospinal fluid

Samples from 1415 neurological patients were used to study the diagnostic value of acid alpha 1-glycoprotein in the lumbar cerebrospinal fluid. The value of analysis for this substance is considered to lie in the detection of non-specific acute-phase reactions of various causes in the CNS with special reference to barrier problems. The large number of pathologically elevated values associated with acute inflammations of the meninges and cerebral parenchyme is particularly striking. The results of the studies are analyzed on the basis of comprehensive control investigations (n = 559).     

Encephalomyelitis syndrome in the cerebrospinal fluid in correlation to disease course criteria in multiple sclerosis

Basing on a classification of the dynamic forms of multiple sclerosis according to prognostic-social aspects and in view to different degrees of defect the incidence of the five possible syndromes of cerebrospinal fluid were subjected to a correlation in 345 cases. In moderate till severe grades of neurologic disturbances and courses of illness an immunoreactive syndrome of cerebrospinal fluid - typically complete to incomplete - was doing found (in ca 40%). The slighter forms of the disease predominantly presented the whole spectrum of possible findings of cerebrospinal fluid; in it the syndromes with unimportant deviations were prevailing. In the course of multiple sclerosis alterations in the constellation of cerebrospinal fluid in manner of a retrograde tendency were scarcely noted. An increase of pathologic parameters in cerebrospinal fluid did rather show the slighter forms, in the severe progredient courses the syndromes turned out to be comparatively constant.     

Water drinking induced in sheep by angiotensin--a physiological or pharmacological effect?

The effect of val5-angiotensin II amide on water drinking in sheep was studied against a background of comprehensive data on arterial blood and cerebrospinal fluid angiotensin II levels in sheep under a variety of physiological conditions. Physiological range of blood angiotensin II concentration is 1-100 ng/100 ml. Intravenous infusion of angiotensin II within the physiological range did not increase water drinking. Intracarotid infusion of angiotensin II, or injection into third ventricle or hypothalamus, consistently caused immediate drinking of large amounts of water. Dosages necessary for effect were in the supraphysiological range. Quantitative examination of data in sheep and other species suggests that a physiological role for angiotensin II in thirst is not proved.     

Diagnostic value of the cerebrospinal fluid-blood lactate quotient in mental disorders in elderly persons]

The lactate levels of cerebrospinal fluid and blood were measured enzymatically and simultaneously in 40 gero-psychiatric patients. After calculating the fluid-blood-lactate-quotients, two distinct groups emerged, whose mean quotients showed significant difference. In the first group (15 patients) with a mean quotient of 1.06, the diagnosis of cerebral arteriosclerosis was clinically confirmed in only one case. In the second group (21 patients) with a mean quotient of 1.42, however, this occurred sixteen times, which represents a proportion of 2/3. Thus, it appears that a higher quotient suggests the diagnosis of cerebral arteriosclerosis. Further examinations are though necessary.     

Cerebrospinal fluid cytologic findings in children with borrelia infections (neuroborreliosis)

The infection of the central nervous system by Borrelia burgdorferi induces usually a mononuclear (lympho-mono-plasmocellular) cytogram of the cerebrospinal fluid in humans. The initial granulocytosis of the liquor cerebrospinalis typical for bacterial infections is transistory only. Such cytologic findings may be misleading to a diagnosis as virus infection. In case of clinical signs (Bannwarth syndrome), typical anamnesis or chronic lymphocytic meningitis the estimation of specific IgG/IgM borrelia antibodies is indicated and the antibiotic therapy should be performed.     

Determination of dipeptidyl aminopeptidase activities in the cerebrospinal fluid

The investigation of enzyme activity in cerebrospinal fluid has been without relevant results for laboratories analysing spinal fluid. For neurochemical purposes, it is interesting that the Substance P is convered by Depeptidyl-aminopeptidase IV (DP IV), liberating dipeptides. The hydrolysis of nitroanilids of the form Xaa-Pro-NHNp in cerebrospinal fluid was analysed using them as peptidases substrates. Finally a method for measuring the activity was proposed.     

Biochemistry of nervous dogs

Previous behavioral studies on a nervous strain of pointer dogs have demonstrated genetic as well as environmental components in the nervous trait. Behaviorally these animals are extremely hypervigilant, with an apparent low threshold to fear and show strong avoidance of humans. In addition, the nervous E strain dogs show an unusually high degree of sensitivity to the mange mite. These observations led to the initiation of studies to determine whether differences exist between the normal A strain and the E strain of dogs at the biochemical level. Although a number of biochemical parameters examined have shown no statistically significant difference between the two strains, the modification of serum creatine phosphokinase (CPK) activity in response to various types of stress does differ as a function of strain—the nervous dogs being less, not more, responsive than the healthy dogs. When not specifically subjected to stress the serum CPK levels in both strains were highly related to age. Significant differences between strains also have been demonstrated in the cerebrospinal fluid acetyl cholinesterase activity levels in older animals. Tryptophan loading experiments, conducted in the presence and absence of the monoamine oxidase inhibitor, tranylcypromine, resulted in no readily observable behavioral modification of either strain and the response of the cerebrospinal fluid 5-hydroxyindoleacetic acid levels was similar for the two strains.     

Listeriosis of the central nervous system in children beyond the neonatal period

Observations on three children with neurolisteriosis (one case of meningitis, two cases of meningoencephalitis, each Serovar 4 b), show that even after the neonatal period, listeriosis must not be ignored in the process of diagnosis and therapy. It is the bacteriological examination of the cerebrospinal fluid, together with the blood culture, and not clinical symptoms and serology that guarantee a timely diagnosis and therapy (ampicillin and gentamicin).     

The temporal dynamics of consolidation and reconsolidation decrease during postnatal development

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.     

Diagnostic assessment of cerebrospinal fluid protein in brain and spinal tumors

The cerebrospinal fluid of 69 patients with tumors of the brain and the spine was examined for total protein content, IgG concentration, IgG total protein quotient, and electrophoretic protein pattern. There is no specific finding in the case of the central nervous system. At best characteristic constellations may be established.     

Quantitative amino acid determination in the serum and cerebrospinal fluid in endogenous depressions

The levels of 20 amino acids were measured in the plasma and cerbrospinal fluid of 41 patients with endogenic depressions. The plasma levels of 12 amino acids were found to be significantly lower in the patients than in the control group, but cerebrospinal fluid levels were significantly lower only in the case of taurine, glutamine, phenylalanine and aginine. Comparison of the same amino acid levels in treated and non-treated patients showed that serine and alpha-aminobutyric acid serum concentrations were higher in the nontreated patients. The tyrosine and phenylalanine levels in the cerebrospinal fluid of the patients who had received medicamentous treatment were higher than in the other group.     

Cerebrospinal fluid diagnosis of multiple sclerosis]

Starting from the knowledge accumulated with respect to the etiopathogenesis and the components of immunoreaction a minimal to maximal program by steps has been developed for the cerebrospinal fluid (CSF) in multiple sclerosis (MS). It is based on fundamental methods (I), special supplementary methods (II), and relatively specific immunological methods (III). For MS five possible conditions of the CSF could be determined from alterations of cells and variations in protein: a (1) typically complete and (2.) typically incomplete immunoreactive encephalomyelitic (encephalitic) syndrome, a (3.) nonspecific CSF-syndrome of low degree and less typical character (in the sense of an acute or subacute irritation syndrome) an (4.) atypical syndrome of a considerable degree, and a (5.) normal condition of the cerebrospinal fluid. The significance of immunoreactive cerebrospinal fluid syndromes to the diagnostic criteria of multiple sclerosis as well as further relatively disease-specific methods (such as the MEM test and MSF assay) of determining cellular immunity, are discussed.     

Transthyretin influences spatial reference memory

Transthyretin (TTR) is a plasma and cerebrospinal fluid carrier for thyroxine and retinol, described also to sequester the amyloid beta peptide. TTR levels have been described as decreased in the cerebrospinal fluid of patients with Alzheimer's disease. In order to investigate the role of TTR in learning and memory, we studied young adult and old TTR-null 129/Sv mice for cognitive performance. In the absence of TTR, 5-month-old mice display spatial reference memory impairment when compared to age-matched wild-type mice. Interestingly, while aging in wild-type mice is associated with a worsening reference memory performance, TTR-null mice show no further impairment with increasing age. As a result, no significant differences were found in this spatial reference task in old mice. Our data show that the absence of TTR seems to accelerate the poorer cognitive performance normally associated with aging.     

Diagnostic value of aspartate aminotransferase in the cerebrospinal fluid

As datum, the range of aspartate aminotransferase in the cerebrospinal fluid of adults was determined on the basis of 153 fluid samples and compared with the values obtained from 356 neurological patients. A significant increase in enzyme activity was established in respect of CVI, polyneuropathy, acute encephalitis, and SAB. It was possible to eliminate any dependence of the aspartate aminotransferase activity on serum activity, total protein, and cell count. The increase in activity of aspartate aminotransferase in the cerebrospinal fluid is thus identified as an independent pathological fact, and thus it can be incorporated in diagnostic routine more particularly in the diagnosis of CVI disorders.     

Influence of dorsal hippocampal lesions and MMP inhibitors on spontaneous recovery following a habituation/classical conditioning head–shake task

The present investigation combined a classical conditioning paradigm with a head–shake response (HSR) habituation task in order to evaluate the importance of dorsal hippocampal neural plasticity to spontaneous recovery. In the first experiment animals exhibited rapid HSR habituation (air stimulus to the ear) and an 85% level of spontaneous recovery following a 24 h inter-session interval. The addition of a brief tone prior to the air stimulus produced a similar pattern of habituation during the first session, but the level of spontaneous recovery was reduced (44%) during Session II. In a second experiment dorsal hippocampal lesioned rats placed on this tone/HSR paradigm responded with an 87% level of spontaneous recovery during Session II; while neocortex lesioned control rats indicated significantly reduced levels of spontaneous recovery (55%). In a third experiment bilateral injections of a general MMP inhibitor, FN-439, into the dorsal hippocampus resulted in high levels of spontaneous recovery (81%); while control rats injected with artificial cerebrospinal fluid displayed a significant attenuation of spontaneous recovery (45%). Finally, animals bilaterally injected with a specific MMP-3 inhibitor into the dorsal hippocampus indicated very similar results to those obtained following FN-439 injection. These findings indicate that animals prepared with dorsal hippocampal lesions, or injections with an MMP inhibitor, revealed an impaired association between the tone and air stimulus thus maximum spontaneous recovery was present 24 h later. Thus, it appears that the dorsal hippocampus influences habituation by conserving responses and reducing spontaneous recovery when a temporally contingent signaling cue is present.     

Concentrating cerebrospinal fluid cells with the sedimentation chamber--comparative methodologic studies

The loss of cerebrospinal fluid cells is considerable when the sedimentation chamber was used. Methodical variations resulted in an increasing cell count on the slide. The absolute number of lymphocytes increased more than that of monocytes. Caused by the higher cell count, especially lymphocytes, the relative values in cell differentiation between lymphocytes and monocytes are changed. For differential counting of lymphocytes, monocytes and other cerebrospinal fluid cell types the elevated cell count is an important factor. Differentiation between subpopulations of lymphocytes by means of this procedure however is problematically because the loss of lymphocytes can be of a selective nature.     

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.