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Biomedical subjects

L Rosengren

Publications and source records attributed to L Rosengren.

At least 55 records · Page 3Linked to original sources

Intrathecal release of pro- and anti-inflammatory cytokines during stroke.

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

Adult↗

Extracellular glial fibrillary acidic protein and amino acids in brain regions of patients with subarachnoid hemorrhage--correlation with level of consciousness and site of bleeding.

The extracellular fluid of two cortical regions was investigated in eight patients who underwent surgery for subarachnoid hemorrhage within 7-96 h after the rupture of an arterial aneurysm. Microdialysis samples, collected from the cortex of the ipsilateral gyrus rectus and temporal lobe for 52-127 h, were analyzed with respect to amino acids and the glial fibrillary acidic protein. In agreement with a previous study, an inverse relation was observed between total amino acid concentration and the level of consciousness. We also found that the concentration of glial fibrillary acidic protein was higher close to the bleeding site. Furthermore, we observed specific changes in the concentration of the protein and certain amino acids which coincided with clinical events such as increased intracranial pressure, vasospasm, ischemia and infarction. Finally, the concentrations of taurine may corroborate its function as an osmoequivalent.

Adult↗

Glial fibrillary acidic protein is increased in the cerebrospinal fluid of preterm infants with abnormal neurological findings.

Glial fibrillary acidic protein (GFAP) is the structural protein of the intermediate filament of astroglia. The aims of the present study were to examine GFAP in the cerebrospinal fluid (CSF) of preterm infants at different postmenstrual ages and to evaluate the potential of GFAP to predict abnormal neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age in preterm infants (n = 17) and full-term infants (n = 9). The levels were five times higher in preterm infants (n = 10) with an abnormal neonatal course and/or an abnormal neurological outcome than in healthy preterm infants. The positive predictive value of a GFAP higher than the 98th percentile of normal infants was 69%, while a GFAP level below this limit invariable predicted a good outcome. Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ between the groups. We conclude that CSF GFAP increases with maturity and that CSF GFAP appears to be a promising marker for perinatal brain damage.

Biomarkers↗

Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke.

BACKGROUND AND PURPOSE: We have previously demonstrated that stroke influences systemic immune responses. The aim of the present study was to investigate patterns of local inflammatory response as a consequence of acute stroke. METHODS: Thirty stroke patients were studied prospectively on days 0 to 3, 7 to 9, 21 to 26, and after day 90 with clinical evaluations, radiological assessments, and analysis of serum and cerebrospinal fluid cytokine levels. RESULTS: Significantly increased levels of interleukin-6 (IL-6) in cerebrospinal fluid (P < .001) were observed in virtually all patients studied compared with healthy control subjects. This increase was observed during the whole observation period but was significantly more pronounced within the first days after stroke onset, with a peak level on days 2 and 3. This initial increase was significantly correlated (r = .65, P = .002) with the volume of infarct measured by MRI 2 to 3 months later. Serum levels of IL-6 in stroke patients were significantly lower than cerebrospinal fluid levels of IL-6 (P = .013) and did not display any significant correlation to the size of the brain lesion. Also, increase in intrathecal but not systemic production of IL-1 beta was observed early during the stroke. Only minor increases of cerebrospinal fluid interferon-gamma levels were observed in two patients. CONCLUSIONS: Our study demonstrates an intrathecal production of IL-6 and IL-1 beta in patients with stroke, supporting the notion of localized inflammatory response to acute brain lesion. In addition, the significant correlation between early intrathecal production of IL-6 and the subsequent size of the brain lesion can be used as a prognostic tool, predicting the size of the brain damage before it is possible to accurately visualize it with radiological methods.

Adult↗

Glial fibrillary acidic protein in the cerebrospinal fluid: a possible indicator of prognosis in full-term asphyxiated newborn infants?

Glial fibrillary acidic protein (GFAP) is the structural protein of intermediate filaments in astroglia. GFAP has extensively been used as a marker of gliosis in neuropathology. It also appears in excessive amounts in the cerebrospinal fluid in various acute brain disorders. Hypoxic-ischemic encephalopathy after perinatal asphyxia is a condition in which levels of GFAP could be expected to be elevated if brain cell damage occurs. We examined levels of GFAP by a sensitive ELISA in the cerebrospinal fluid of full-term infants between 12 and 48 h after birth. Cerebrospinal fluid-GFAP increased 5-fold in infants after perinatal asphyxia compared with a reference group (675 versus 137 ng/L, p < 0.001). The levels of GFAP also increased gradually in accordance with the severity of the neurologic symptoms ranked as degree of hypoxic-ischemic encephalopathy. We conclude that the cerebrospinal fluid levels of GFAP might be an important adjunct in the neonatal assessment of infants subject to perinatal asphyxia, and together with other neuronal or glial proteins, it might also help in defining temporal relationships in asphyxia.

Asphyxia Neonatorum↗

Analysis of glial fibrillary acidic protein in the cerebrospinal fluid of children investigated for encephalopathy.

The clinical application of a newly developed highly sensitive ELISA method (20) to assay glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid (CSF) was investigated in children and adolescents with neurological disorders. GFAP analysis was explored as a tool to differentiate disorders with ongoing astrocytosis. A consecutive series of 34 subjects, 17 boys and 17 girls, with nonprogressive and progressive neurological encephalopathies was compared to 10 healthy controls. The mean CSF GFAP concentration of the controls was 60.6 +/- 54 ng/l (SD). The group of 24 subjects (12 boys and 12 girls) with progressive neurologic disorders had higher mean CSF GFAP levels than the group of 10 subjects (5 boys and 5 girls) with non-progressive disorders, 222.6 +/- 186 and 127.5 +/- 86 ng/l, respectively. The progressive encephalopathies differed significantly from controls (p < 0.01) while the non-progressive did not. The mean GFAP concentration of the epilepsy cases (n = 18) and non-epilepsy cases (n = 16) was 212.9 +/- 196 and 174.0 +/- 132 ng/l, respectively. The epilepsy cases differed significantly from controls which could be explained by the dominance of progressive cases (15 out of 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

The IOP-IOL. A probe into the eye.

The intraocular lens (IOL) implant can be looked upon as a probe into the space of the eye. Adapting that view, it is logical to furnish the IOL-probe with biomedical sensors that would explore its environment. A sensor is presented for continuous monitoring of intraocular pressure (IOP), incorporated in the haptics of an IOL. The sensor consists of a capacitative spiral circuit, needing no energy, correlating its resonance frequency to the actual IOP. This resonance frequency is remotely and non-invasively detected by an external device located in a spectacle frame.

Biosensing Techniques↗

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↗

Aspects of abstinence after morphine ingestion.

Sprague-Dawley male rats were intoxicated with morphine, using an ingestion method where exposed and control rats received equivalent amounts of calories and nutrients. The degree of physical dependence on morphine was demonstrated by studying and quantifying abstinence symptoms after withdrawal or after administration of opiate antagonists. The aims of the study were (1) to further enlighten the specificity and validity of the intoxication method concerning physical dependence, and (2) to determine whether some of the abstinence signs might be of value to facilitate quantitation of the degree of physical dependence on morphine, with diet and fluid intake being maintained under control. Withdrawn rats showed a decreased fluid diet intake and a body weight loss, the latter partly due to anorexia. Other mild abstinence signs were irritation, tremor and some motor excitation. The body weight loss during the first day of morphine withdrawal was proportional to the accumulated drug dose (between 25 and 300 mg morphine PO/kg b.wt.). However, prolonged morphine treatment on one dose (340 mg/kg b.wt.) did not reinforce the body weight changes caused by morphine withdrawal. The succeeding weight gain some days after morphine withdrawal was not entirely dependent on the amount of fluid diet intake. Methadone was shown to partially block the decrease in diet intake and the weight loss seen during morphine withdrawal. The naloxone-precipitated withdrawal symptoms were motor excitation, cholinergic signs, body weight loss, diarrhoea and decreased diet intake. The weight loss 2 hr after naloxone administration to long-term intoxicated rats was proportional to the naloxone dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗

Neurotransmitter uptake in various brain regions of chronically morphinized rats.

Rats were long-term morphine-intoxicated by a fluid-diet model ensuring an equal nutrient intake in morphinized and control rats. Uptake of neurotransmitters and D-ala2-met5-enkephalinamide (Enk) was studied in the particulate fractions (obtained at 10,000 g) from well defined brain regions of long-term intoxicated and morphine withdrawn rats. In control animals the accumulation of [3H]glutamate and [3H]gamma-aminobutyric acid (GABA) reached the highest tissue/medium (T/M) ratio values, 30-120, in the regions studied while monoamine T/M values were 2-10. No active uptake of [3H]Enk could be demonstrated. Striatum showed the most evident modifications in neurotransmitter uptake. In this region the equilibrium T/M ratio for [3H]glutamate and [3H]GABA was significantly lower in intoxicated rats versus controls. Moreover, the T/M ratio for [3H]5-hydroxytryptamine (5-HT) was lower, while that for [3H]dopamine (DA) was higher in abstinent rats in comparison with the controls. [3H]glutamate and [3H]GABA uptakes were also significantly lower, respectively, in frontal cortex, hippocampus and brain stem in intoxicated rats, while [3H]5-HT uptake was significantly lower in hypothalamus after morphine withdrawal. The possible involvement of the endogenous opioid system in the etiology of the alterations is discussed.

Administration, Oral↗

Chronic effects of dichloromethane on amino acids, glutathione and phosphoethanolamine in gerbil brain.

Mongolian gerbils were exposed to dichloromethane for three months by continuous inhalation at 210 ppm. Total free tissue amino acids, glutathione, and phosphoethanolamine were determined in the vermis posterior of the cerebellum and the frontal cerebral cortex. These two brain areas were chosen because humans occupationally exposed to dichloromethane have shown abnormalities in the electroencephalogram of the frontal part of the cerebral cortex. This study showed that long-term exposure of gerbils to dichloromethane (210 ppm) for three months leads to decreased levels of glutamate, gamma-aminobutyric acid, and phosphoethanolamine in the frontal cerebral cortex, while glutamine and gamma-aminobutyric acid are elevated in the posterior cerebellar vermis.

Amino Acids↗

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↗