Immunologic and neurobiologic characteristics support that interstitial cystitis is a heterogeneous syndrome.
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Cell Count↗
Biomedical subjects
K Haglid
Publications and source records attributed to K Haglid.
Antisense inhibition of BCL-2 expression induces retinoic acid-mediated cell death during differentiation of human NT2N neurons.
Changes in expression of the proto-oncogene Bcl-2 are well known in the developing brain, with a high expression level in young post-mitotic neurons that are beginning the outgrowth of processes. The physiological significance of the Bcl-2 up-regulation in these neurons is not fully understood. We used a differentiation model for human CNS neurons to study the expression and function of Bcl-2. NT2/D1 human neuronal precursor cells differentiated into a neuronal phenotype in the presence of 10 microM retinoic acid for 3-5 weeks. This concentration of retinoic acid was not toxic to undifferentiated NT2/D1 cells but was sufficient to up-regulate the BCL-2 protein in 6 days. The BCL-2 levels increased further after 3 weeks, i.e. when the cells started to show neuronal morphology. Inhibition of the accumulation of endogenous BCL-2 with vectors expressing the antisense mRNA of Bcl-2 caused extensive apoptosis after 3 weeks of the retinoic acid treatment. The loss of neuron-like cells from differentiating cultures indicated that the dead cells were those committed to neuronal differentiation. Death was related to the presence of retinoic acid since withdrawal of retinoic acid after 16 days of treatment dramatically increased cell surviving. The ability of BCL-2 to prevent retinoic acid-induced cell death was also confirmed in undifferentiated NT2/D1 cells that were transfected with a vector containing Bcl-2 cDNA in sense orientation and exposed to toxic doses (40-80 microM) of retinoic acid. Furthermore, down-regulation of BCL-2 levels by an antisense oligonucleotide in neuronally differentiated NT2/D1 cells increased their susceptibility to retinoic acid-induced apoptosis. These results indicate that one function of the up-regulation of endogenous BCL-2 during neuronal differentiation is to regulate the sensitivity of young post-mitotic neurons to retinoic acid-mediated apoptosis.
Apoptosis↗
A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis.
Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.
Acceleration↗
A new model for diffuse brain injury by rotational acceleration: II. Effects on extracellular glutamate, intracranial pressure, and neuronal apoptosis.
The aim of this study is to monitor excitatory amino acids (EAAs) in the extracellular fluids of the brain and to characterize regional neuronal damage in a new experimental model for brain injury, in which rabbits were exposed to 180-260 krad/s2 rotational head acceleration. This loading causes extensive subarachnoid hemorrhage, focal tissue bleeding, reactive astrocytosis, and axonal damage. Animals were monitored for intracranial pressure (ICP) and for amino acids in the extracellular fluids. Immunohistochemistry was used to study expression of the gene c-Jun and apoptosis with the terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) technique. Extracellular glutamate, glycine, and taurine increased significantly in the hippocampus within a few hours and remained high after 24 h. Neuronal nuclei in the granule layers of the hippocampus and cerebellum were positive for c-Jun after 24 h. Little immunoreactivity was detected in the cerebral cortex. c-Jun-positive neuronal perikarya and processes were found in granule and pyramidal CA4 layers of the hippocampus and among the Purkinje cells of the cerebellum. Also some microglial cells stained positively for c-Jun. TUNEL reactivity was most intense at 10 days after trauma and was extensive in neurons of the cerebral cortex, hippocampus, and cerebellum. The initial response of the brain after rotational head injury involves brain edema after 24 h and an excitotoxic neuronal microenvironment in the first hour, which leads to extensive delayed neuronal cell death by apoptosis necrosis in the cerebral cortex, hippocampus and cerebellum.
Acceleration↗
Antiserum against S-100 protein prevents long term potentiation through a cAMP-related mechanism.
Long term potentiation (LTP) was induced in the CA1 region of rat hippocampal slices by tetanization of the Schaffer collaterals. Local pretreatment of CA1 with serum of rabbits immunized against S-100 prevented the potentiation. However, treatment of the slices with a membrane permeant cAMP analogue, such as 8-Br-cAMP, could protect against the blocking effect of anti S-100 serum. We suggest that in the rat endogenous S-100b is involved in transduction mechanisms during LTP induction, via its ability to stimulate adenylate cyclase. Possible mechanisms of this action are discussed.
8-Bromo Cyclic Adenosine Monophosphate↗
Involvement of S-100 protein in anoxic long-term potentiation.
In in vitro rat hippocampal slices a short period (2 min) of hypoxia resulted in lasting potentiation of the population spike transynaptically evoked in CA1 by stimulation of Schaffer collaterals ("anoxic LTP"). Pretreatment of slices with antiserum against S-100 protein fully prevented this anoxic LTP. Since also "classical" (i.e., induced by high-frequency electrical stimulation) long-term potentiation is prevented by anti S-100 serum, this represents one more important similarity between these events.
Action Potentials↗
Decreased levels of S-100 protein in non-ulcer interstitial cystitis.
Interstitial cystitis (IC) is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that IC is a heterogeneous syndrome. As compared to classic IC, the non-ulcer type of IC appears to be different concerning symptomatic, endoscopical and histological findings, as well as in response to various forms of treatment. S-100 is a neural protein considered to be located primarily in the axons. To explore further the neurogenic nature of the disease, we compared bladder wall S-100 content in controls and in patients with classic and non-ulcer IC. We noticed a decrease in S-100 content in non-ulcer IC as compared to controls. This may be an expression of altered peripheral innervation in non-ulcer IC, which, in turn, may be an indication of primary neurogenic etiology. The difference in S-100 content between classic and non-ulcer IC supports the hypothesis that they represent separate entities, which may explain differences in response to various treatments.
Adult↗
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↗
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↗
Brain lipid composition in guinea pigs after intrauterine exposure to perchloroethylene.
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Animals↗
Production of transferable neuronotrophic factor(s) by human midgut carcinoid tumour cells; studies using cultures of rat fetal cholinergic neurons.
A co-culture system was established between human midgut carcinoid tumour cells and rat fetal cholinergic neurons. In monocultures in serum-free media, only tumour cells survived, while neurons deteriorated. In serum-free co-cultures, neurons displayed outgrowth of neuritic processes. Neurons of neuronal serum-free monocultures thrived if supplemented with conditioned media from tumour cell cultures grown serum-free. This indicates that tumour cells produce transferable growth factor(s) with potent neuronotrophic actions. Immunocytochemical studies indicate that this growth factor resembles nerve growth factor immunologically, since tumour cells were strongly immunoreactive after incubation with a rabbit anti-nerve growth factor antiserum, and furthermore expressed immunoreactive nerve growth factor receptors.
Animals↗
Immunocytochemical investigations on the presence of neuron-specific antibodies in the CSF of Parkinson's disease cases.
The CSF and sera of 7 patients with Parkinson's disease were investigated immunocytochemically, in order to see if antibodies were present which recognized DA-ergic cell bodies in glutaraldehyde fixed rat brain. In 2 patients a marked labeling of DA-ergic neurons in the substantia nigra was observed, identified by anti-DA antiserum and by 6-OHDA induced degeneration, but also other neurons in the ventral mesencephalon were recognized. The other patients were weakly positive or negative. Sera gave unspecific labelling of all neurons. In one patient the sub-classes of IgG were investigated and found to be of IgG3 (labeling nerve terminals) and of IgG1-2, low affinity type (recognizing perikarya). The epitopes recognized have not been identified, but are unlikely to be DA-like, since blocking experiments and ELISA-tests gave negative results. The possible clinical importance of the results are discussed.
Aged↗
Dopaminergic terminals in the rat locus coeruleus: an immunocytochemical investigation.
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Animals↗
Brain lipid changes in rats exposed to xylene and toluene.
Rats were continuously exposed to vapors of xylene (320 ppm) for 30 or 90 days, other groups were exposed to toluene (320 ppm) for 30 days. After termination of exposure, different brain regions were removed for the determination of their lipid contents and ethanolamine phosphoglyceride fatty acid patterns. The 2 solvents had different effects on the animals. Xylene exposure resulted in limited transient changes. After 30 days exposure an increase in the liver to body weight ratio and a decrease in linoleic acid of ethanolamine phosphoglyceride in the cerebral cortex were observed. These changes were normalized after 90 days exposure. Toluene exposure, on the other hand, resulted in decreased weights of the body, of the brain as a whole and of the cerebral cortex. Liver weights were unchanged. Total phospholipids were found to be reduced in the cerebral cortex where also a slight increase in phosphatidic acid was observed. In this brain region a minor fatty acid of ethanolamine phosphoglyceride, 22:5 (n-3), was decreased. No changes were observed in the brainstem. The data on brain weights and lipid composition after exposure to toluene indicates a breakdown of phospholipids resulting in a loss of gray matter. The mechanism for these changes is uncertain but may involve degradation of phospholipids by phospholipase D. The effective metabolism of xylene and toluene seem to protect from fatty acid changes of brain phospholipids previously observed after exposure to chlorinated ethylenes.
Animals↗
Antibodies in cerebrospinal fluid of some Alzheimer disease patients recognize cholinergic neurons in the rat central nervous system.
The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.
Acetylcholine↗
Immunocytochemical localisation of caligulin-like immunoreactivity in rat tissues.
The cellular localisation of caligulin-like immunoreactivity (caligulin-LI) in rat central and peripheral tissues was studied using antibodies against bovine brain caligulin raised in rabbits. Both immunofluorescence and immunoperoxidase techniques were used to demonstrate caligulin-LI in paraformaldehyde fixed tissues. Certain neurons in the cerebral cortex, basal ganglia and brain stem contained caligulin-LI. In the cerebellum a majority of Purkinje cells were labelled with immunoreactive material localised to dendrites, perikarya and axons. In the gastrointestinal tract some neurons in Auerbach's and Meissner's plexa contained caligulin-LI. Ligation of the sciatic nerve caused accumulation of immunoreactive material both proximal and distal to the crush. A non-neuronal localisation of caligulin-LI could also be demonstrated, e.g., in parts of the renal tubular system, in the islets of Langerhans and in certain enteroendocrine cells. The specific localisation of caligulin-LI in some but not all neurons of the rat brain and gastrointestinal tract suggests a specific function of caligulin in central and peripheral nervous mechanisms.
Animals↗
Differentiation markers (S-100, GFAP, NSE and D2) in fetal rat brain cells during malignant transformation in cell culture.
Malignant cell lines obtained by ethylnitrosourea (EtNU)-induced transformation of fetal rat brain cells in culture express protein markers of different types of neural cells. These are the nervous system-characteristic S-100 protein; glial fibrillary acidic protein (GFAP); neuron-specific-enolase (NSE), and the D2-cell adhesion molecule. S-100 protein was absent in fetal brain cells in culture, but gradually appeared in the later stages of malignant transformation and further increased at onset of rapid growth of atypical cells (stage IV). GFAP and D2 were weakly expressed in primary fetal brain cells and did not change throughout malignant transformation. NSE was present in both normal and carcinogen-treated fetal brain cells, and increased at later stages of malignant transformation. From stage III (40-100 days) some cultures were strongly positive and some negative, and the same was seen in the resulting tumorigenic cells about 100 days later. In conclusion the stepwise process of malignant transformation of brain cells in culture ended with a stable phenotype of cells capable of expressing varying types of differentiation markers. The presence of these markers in rat brain cells undergoing malignant transformation may indicate that EtNU given at 18th days of gestation is acting on multipotent neuroectodermal cells.
Animals↗
Immunohistochemical distribution of S-100 antigen in the urinary system of man and rat.
The immunohistochemical distribution of S-100, a protein originally isolated from the brain, has been investigated at the light and electron microscopic levels in rat and man urinary systems. In both species the antigen essentially exhibited the same location, restricted, with different degrees of staining, to certain cells in the kidney, i.e. collecting tubules, thin limbs of Henle's loop and renal papillae.
Animals↗