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Biomedical subjects

A Hamberger

Publications and source records attributed to A Hamberger.

At least 55 records · Page 3Linked to original sources
PubMed1994

Changes in neurofilament protein NF-L and NF-H immunoreactivity following kainic acid-induced seizures.

Postlesion plasticity of neuronal processes might contribute to secondary spontaneous seizures after kainic acid administration. In this study, neurofilament (NF) proteins were examined following intraperitoneal injection of kainic acid, and special reference was given to temporal changes in quantity and quality of the NF light (NF-L) and heavy (NF-H) subunits. A pronounced decrease in phosphorylation-related immunoreactivity of NF-H occurred as early as 1 day after the injection in the amygdala/pyriform cortex, hippocampus, striatum, and dorsal cerebral cortex. A shift of NF-H from the phosphorylated to nonphosphorylated form was evident in immunoblots, suggesting dephosphorylation contributed to the decrease. Decreases in NF-L and phosphorylated NF-H contents in the limbic structure at 3 days were correlated with the increasing kainic acid doses from 2.5 to 10 mg/kg. The degradation pattern in immunoblots with antibodies against NF-L indicated that the decrease in NF-L was probably due to calcium-activated proteolysis. NF-L and phosphorylated NF-H contents secondarily increased from 9 days onward, with approximately 20% above the control level of phosphorylated NF-H immunoreactivity at 27 days in the amygdala/pyriform cortex and ventral hippocampus. Immunohistochemical examination of the hippocampus revealed that an increase of NF staining in the mossy fiber system may contribute to the NF recovery in this region. Furthermore, the temporal changes of NF-L and phosphorylated NF-H contents were positively correlated with those of the neuronal cell adhesion molecule, a neuritic growth cone marker, substantiating postlesion regenerative reactions of NF proteins. Functional consequences of the NF plasticity remain to be identified.

Animals↗
PubMed1993

Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders.

The cerebrospinal fluid (CSF) of 47 children and adolescents with autism was analyzed for the contents of two astroglial proteins, the glial fibrillary acidic protein (GFA) and S 100. The results were contrasted with those obtained in similarly aged cases with other neuropsychiatric disorders (n = 25) and in normal children (n = 10). S-100 did not discriminate the groups from each other. However, GFA in autism and autistic-like conditions was at a level almost three times that in the normal group. The results could implicate gliosis and unspecific brain damage in autism. An alternative model would be increased synapse turnover regardless of underlying cause.

Adolescent↗
PubMed1993

Metabolic manipulation of neural tissue to counter the hypersynchronous excitation of migraine and epilepsy.

Very prominent in the large biochemical data bank on epilepsy, is the almost "universal" finding that a familial or environmental predisposition towards epilepsy, as well as the earliest signs preceding other forms of hypersynchronous excitation, coincide with an altered glutamate metabolism. Hence, it has become increasingly apparent that glutamate occupies a central position in the development of epilepsy or in the onset of a migraine incident. The importance of glutamate is explained by a variety of functions in the CNS: as a dominant constituent of many proteins, by its intermediary role in linking energy metabolism to that of many other amino acids, and as the virtually exclusive precursor of GABA. Moreover, glutamate serves as the primary substrate in ammonia detoxification and the product, glutamine, actively participates in CSF water homeostasis. Finally, by its direct electrophysiological and metabolic actions on neurons and glia, via at least four distinct types of receptor proteins, glutamate is implicated in a number of critical mechanisms of information. These include neuronal excitatory modulation, intracellular Ca2+ redistribution, and key metabolic (phosphorylation) mechanisms. The phenomena, when exaggerated due to excessive extracellular glutamate levels, may cause pathological effects such as hypersynchrony--epilepsy, Spreading Depression-migraine, high internal Ca(2+)--damage, impaired phosphorylation/dephosphorylation-necrosis, among others. Not surprising therefore that severe epilepsy may eventually cause CNS cytoarchitectural and metabolic damage, or conversely, that neural tissue trauma not infrequently gives rise to epilepsy many years later. Both conditions are associated with a persistent, excessive leakage or release of glutamate into the extracellular milieu. An electrophysiological and neurochemical commonality between migraine and epilepsy has also been noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Biochemical correlates to cortical dysplasia, gliosis, and astrocytoma infiltration in human epileptogenic cortex.

The study provides detailed biochemical correlates to the common histopathological diagnoses in epilepsy. A dot immunobinding procedure was used for quantification of NSE, GFA, S-100, NCAM, NF 68 and NF 200. The material consisted of samples from 48 patients either selected for surgical treatment of partial epilepsy or for disorders not related to epilepsy. The histopathological diagnosis of the epileptic cases was: MCD (mild cortical dysplasia, microdysgenesis), gliosis, astrocytoma, ganglioglioma, oligodendroglioma and single cases. The concentration in non-epileptic white matter, in per cent of that in grey matter was: NSE, 85; GFA, 175; S-100, 117; NCAM, 43; NF 68,227 and NF 200, 173. The concentration of NSE as well as of GFA was close to normal in the specimens of the MCD and gliosis groups and of one subgroup of the astrocytomas. There was a striking inverse relationship of the GFA vs the NSE concentrations in the whole material. The concentrations of S-100 showed no such inverse relationship to NSE levels. In all the epileptic groups, total NCAM was lower than 50% of that of the non-epileptic group. The mean NF 68 and NF 200 concentration in the gliosis and astrocytoma groups was 75% of that of the non-epileptic group while the corresponding value for the MCD group was 50%. There was a positive correlation of immunochemically determined GFA and the histopathological gliosis score in the samples of epileptogenic cortex. There was no correlation between the concentration of GFA in the samples and the duration of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Co-variation of free amino acids in human epileptogenic cortex.

The concentration of free amino acids was measured in 41 surgically removed samples of human epileptogenic brain and in 7 specimens of non-epileptic brain tissue, removed during surgery for meningiomas, etc. The material was subdivided according to the neuropathological diagnosis: mild cortical dysplasia (MCD), gliosis astrocytoma infiltration and a histologically heterogeneous group. The non-tumoral epileptogenic samples had five times higher than normal concentration of ethanolamine and 50% elevated concentration of glycine. The concentration of other neurotransmitter amino acids did not differ markedly between epileptogenic and non-epileptic samples. The concentration of neurotransmitter amino acids showed a strong correlation with the enzyme neuron specific enolase (NSE) and were low in most samples with astrocytoma infiltration. On the other hand, tyrosine and leucine had higher concentrations in samples with lower NSE concentration. Factor analysis of the amino acids revealed four groups of covarying compounds in the brain samples, first, a neurotransmitter group, including aspartate, glutamate, GABA and phosphoethanolamine. Another group contained ethanolamine, glutamine, glycine and taurine. Factor analysis on corresponding extracellular amino acids showed two groups, the first being a "neurotransmitter" group, containing serine, taurine phosphoethanolamine and ethanolamine in addition to aspartate and glutamate. The other group consisted of asparagine, glycine, alanine, tyrosine, valine, phenylalanine, isoleucine and leucine.

Adolescent↗
PubMed1993

Neuronal and glial marker proteins in encephalopathy associated with acute liver failure and acute hyperammonemia in the rabbit.

Neuronal and glial cell marker proteins were quantified in order to evaluate the possibility of increased proteolysis in the brain of rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced by a two-stage devascularization procedure. Acute hyperammonemia was induced by a prolonged infusion of ammonium acetate, which simulates the plasma ammonia level in acute liver failure. Control animals received an infusion of sodium/potassium acetate. After development of severe encephalopathy, the animals were sacrificed (13.7 +/- 1.3 hours for rabbits with acute liver failure and 20.2 +/- 0.8 hours for rabbits with hyperammonemia) (x +/- S.E.M./n = 6) and their brains were dissected into cerebral cortex, hippocampus, cerebellum and brain stem. The total protein content and the concentrations of the neuronal cell marker proteins NSE (neuron specific enolase), NF68 and NF200 (68 kD and 200 kD neurofilament polypeptides) and the glial cell marker proteins GFAP (glial fibrillary acidic protein) and S-100 were determined. Total protein content was decreased in the brain stem in acute hyperammonemia only. The content of neuronal and glial cell markers was not affected in either of the two conditions. However, low molecular weight proteolytic fragments of the NF 68 kD polypeptide were observed in the hippocampus of three out of six animals in both experimental groups. No proteolytic degradation of GFAP was observed. The results show that, in experimental encephalopathy due to acute liver failure and acute hyperammonemia, no major changes occur in the marker proteins. The finding of proteolytic fragments of the NF68 polypeptide indicates that the neuronal population is affected prior to glial alterations. These findings are in agreement with the concept that acute hepatic encephalopathy is reversible and induces only slight structural changes.

Acute Disease↗
PubMed1993

Effect of long-term vigabatrin therapy on GABA and other amino acid concentrations in the central nervous system--a case study.

A 32 year old patient with refractory complex partial seizures was treated with vigabatrin for 3.5 years. Before starting treatment and at 42 months, lumbar punctures were done and the CSF analyzed for amino acids including GABA. Although the patient experienced a 50% seizure reduction, he underwent a left sided temporal lobectomy, and the tissue sample was also analyzed for amino acid content. It was found that vigabatrin caused a three-fold increase in total and free GABA in both the tissue sample and CSF. There were no other significant changes in the other amino acids analyzed. Seizure reduction seen initially was maintained over the long-term observation period. The finding of a specific increase of GABA in brain tissue and CSF of this patient treated with vigabatrin provides additional support to the concept that the primary effect of vigabatrin is as a selective enzyme activated irreversible inhibitor of GABA transaminase.

Adult↗
PubMed1993

Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy.

Asphyxiated (n = 27) and control infants (n = 25) were subjected to spinal taps. Amino acids were measured with liquid chromatography and the degree of hypoxic-ischemic encephalopathy was determined in each case. In asphyxiated infants, the concentrations of aspartate and glutamate were 286% and 387% (p < or = 0.01 and p < or = 0.05) of the control values, respectively. The cerebrospinal fluid aspartate levels were significantly (p < or = 0.05) higher in the group with severe (3.4 mumol/l) compared with the group with mild hypoxic-ischemic encephalopathy (1.0 mumol/l). Glutamate was also higher in the group with severe (12.3 mumol/l) than in the groups with mild (2.7 mumol/l) or moderate (3.2 mumol/l) hypoxic-ischemic encephalopathy (p < or = 0.05). High concentrations of excitatory amino acids were present in the CSF of asphyxiated infants which may exert excitotoxic effects.

Amino Acids↗
PubMed1992

Neurochemical effects of vagus nerve stimulation in humans.

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.

Adult↗
PubMed1992

Biphasic changes in NCAM level after an NMDA lesion to the hippocampal formation: a quantitative dot-immunobinding assay.

With a quantitative dot-immunobinding assay, the time course changes of neuronal cell adhesion molecule (NCAM) concentrations and total tissue content were monitored in the rat hippocampus after a 40 nmol NMDA injection. A biphasic alteration was observed; a decrease occurred at day 3, an increase at day 30. The time course of changes differed from that of the glial fibrillary acidic protein (GFAP), a marker for reactive astroglial cell, but was similar to that for the markers of sprouting neurites, i.e., low (L) and high (H) molecular weight subunits of the neurofilament polypeptides. It is suggested that NCAM is implicated in the onset of neurite sprouting in the hippocampus after an excitotoxic trauma.

Animals↗
PubMed1992

Proteolysis of filament proteins in glial and neuronal cells after in vivo stimulation of hippocampal NMDA receptors.

An intrahippocampal injection of N-methyl-D-aspartate induced the appearance of degradation products of both the 68 kiloDalton neurofilament protein and the glial fibrillary acidic protein, as revealed by immunoblot techniques. The degradation of these two filament proteins was maximal at 10 days after the lesion. The degradation patterns were similar to those induced with calpains or calcium in vitro. There were no degradation effects on the 200 kD neurofilament protein as tested with both mono- and polyclonal antibodies. Consequently, the neuronal degeneration after excessive activation of NMDA receptors appears to involve calcium activation of proteolytic enzymes. The effects on the glial proteins are probably secondary to neuronal damage but could be related to calcium dependent processes.

Animals↗
PubMed1992

A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children.

In the present study we describe a sensitive ELISA for determination of glial fibrillary acidic protein (GFAP). To validate the method combined determinations of GFAP and S-100 protein were performed in cerebrospinal fluid (CSF) of normal children and children with autism. The GFAP ELISA is of sandwich type and uses the biotin-avidin system. Sensitivity was 16 pg/ml. Between-day precision was 0.079 (coeff. of variance). S-100 protein concentrations were measured using a commercially available ELISA kit. Normal CSF from children and young adults were analysed. The CSF levels of GFAP in normal children were low (16-163 pg/ml). Both GFAP and S-100 protein concentrations correlated with age (P < 0.01 and P < 0.05, respectively), but the GFAP increment was more pronounced, probably reflecting the age-dependent expansion of the fibrillary astrocytes in the central nervous system (CNS). GFAP levels in children with infantile autism were higher than those in normal children of the same age range. S-100 protein concentrations were similar in both groups. High levels of GFAP in combination with normal S-100 protein concentrations in CSF indicates reactive astrogliosis in the CNS. In conclusion, the sensitive ELISA described makes it possible to measure low levels of GFAP present in the CSF of children. Combined assays of GFAP and S-100 protein can be used to discriminate between acute and chronic brain disorders in children.

Adolescent↗
PubMed1992

Elevated CSF glutamate in Rett syndrome.

The concentration of free amino acids was measured in the cerebrospinal fluid of four patients with Rett syndrome. The reference material were patients with autistic disorder who had CSF aminoacid levels similar to those reported for healthy children. The concentration of glutamate-but of no other amino acid-was markedly elevated in the CSF of the RS patients. The results are discussed in the context of excitotoxicity in neurodegenerative disease.

Adult↗
PubMed1992

In vivo activation of kainate receptors induces dephosphorylation of the heavy neurofilament subunit.

Injection of kainic acid (KA) into the rat hippocampus reduced the phosphorylation-related immunoreactivity of the heavy subunit of neurofilament proteins (NF-H). The effect was demonstrated quantitatively with a dot-immunobinding assay and qualitatively by immunoblotting with monoclonal antibodies against phosphorylation-dependent and nonphosphorylation-related epitopes of NF-H. The KA-induced reduction affected 50% of the phosphorylated NF-H in half of the hippocampus after 48 h. At the same time, the nonphosphorylation-related NF-H immunoreactivity increased as revealed by immunoblotting, indicating a shift from phosphorylated to nonphosphorylated NF-H. The effects on NF-H preceded a decrease in content of the neuron-specific enolase, a soluble neuronal cytoplasmic protein. No alterations of the light subunit of neurofilament proteins occurred, suggesting that KA has a preferential effect on NF-H phosphorylation. N-Methyl-D-aspartate administered similarly did not lead to a rapid dephosphorylation of NF-H. We propose that kainate receptor-mediated dephosphorylation in NF-H is involved in the signal transduction of excitatory amino acids with consequences for neuronal functions dependent on intermediary filament phosphorylation.

Animals↗
PubMed1991

The effect of an N-methyl-D-aspartate lesion in the hippocampus on glial and neuronal marker proteins.

The study employed an immunochemical quantification of brain cell marker proteins in addition to quantitative morphology in order to provide a more multifacetted and characterized model for an excitotoxic CNS lesion. The importance of the approach in the evaluation of the potential of neuroprotective agents is emphasized. The S-100 protein, the glial fibrillary acidic (GFA) protein, neuron specific enolase (NSE) and neuronal intermediary filament polypeptides (NF 68 and NF 200) were measured with a dot-immunobinding assay, 3-30 days after a unilateral injection of N-methyl-D-aspartate (NMDA) in the left dorsal hippocampus of the rat. After 3 days, the neuronal cell loss averaged 80% in the hippocampus. The S-100 content was reduced 3 days after injection, but was 150% of control at 30 days. GFA increased constantly from days 3 to 30. The neuronal marker proteins were all markedly reduced 7 days after injection. However, at 30 days, NF 68 and NF 200 were close to control (80%). Increasing content would reflect regeneration and sprouting of neurites. The content of the neuronal cytoplasmic marker, NSE, was significantly lower than control also at 10 and 30 days, although a gradual recovery could be traced.

Animals↗
PubMed1991

Intracerebral distribution of DL-2-amino-phosphonopentanoic acid (AP5) and the dissociation of different types of learning.

Chronic intraventricular infusion of the selective NMDA receptor antagonist AP5 appears to cause an impairment of spatial but not visual discrimination learning. However, Goddard (1986) has questioned whether this dissociation in task-selectivity reflects a difference in the underlying neural mechanisms or differential drug diffusion. Two experiments conducted to address this issue established (a) that chronic intraventricular infusion of AP5, at a dose sufficient to cause a spatial learning impairment, results in a relatively uniform distribution of the drug across the brain, and (b) that chronic bilateral intracortical infusion at sites very close to visual cortex also fails to impair visual discrimination learning. These findings argue against differential diffusion being a major cause of the sensitivity of spatial but not visual discrimination tasks to AP5, and raises the possibility that representational and procedural memory tasks may depend upon distinct cell-biological mechanisms of plasticity.

2-Amino-5-phosphonovalerate↗
PubMed1991

Microdialysis sampling of the neuronal environment in basic and clinical research.

Microdialysis is a technique for sampling extracellular fluid (ECF) which has been employed in brain research for about 10 years, and is now in experimental and clinical use in a number of biomedical disciplines. We report on microdialysis of neuroactive amino acids in the central nervous system (CNS) and discuss some technical problems of microdialysis, such as tissue reactions, calibration and the difficulties involved, as well as strategies for determination of the true extracellular concentration of various compounds. Possible mechanisms of nerve cell death in ischaemia and hypoglycaemia are among the factors that have been elucidated using data obtained by microdialysis. The neuronal environment overflows with excitatory amino acids both in brain ischaemia and in hypoglycaemia.

Animals↗