Autologous mesenchymal stem cell transplantation in stroke patients.
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Control Groups↗
Biomedical subjects
Jacques De Keyser
Publications and source records attributed to Jacques De Keyser.
A fatal demyelinating illness in a young woman 10 weeks post partum.
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Adrenal Cortex Hormones↗
Cluster-like headache aura status.
We describe a patient with successive attacks (40 to 90 minutes) of cluster-like headache associated with aphasia, and contralateral hemihypesthesia and hemiplegia. The condition can best be described as cluster-like headache aura status.
Adult↗
Neuroprotection in acute ischemic stroke.
Neuroprotection of patients with acute ischemic stroke should start at the scene and continue in the ambulance with the assessment and treatment of the airway, breathing, circulation, body temperature, and blood glucose. The key goal in eligible patients should be fast vessel recanalization with intravenous recombinant tissue-type plasminogen activator Results from a meta-analysis suggest that systemic thrombolysis is effective when given within 4.5 hours after stroke onset. The time window extends to 6 hours for patients undergoing intravascular thrombolysis. Acute stroke patients should be admitted to stroke care units. A crucial component of neuroprotection is the prevention of secondary brain damage, which can be caused by hypoxemia, hypotension, hyperthermia and hyperglycemia. This can be achieved by avoiding complications, e.g. aspiration, and intensive control of oxygenation, hydration and blood pressure, body temperature, blood glucose, and cardiac monitoring. Neuroprotective agents are designed to try to salvage brain tissue within the penumbra. Thus far, despite promising preclinical studies, clinical trials with neuroprotective drugs in acute ischemic stroke have been disappointing. However, we have been able to identify many of the factors that were responsible for these failures, and better-designed clinical trials with neuroprotective drugs should look more promising. Mild induced hypothermia is another form of neuroprotective treatment that is currently being investigated in acute stroke.
Animals↗
1H Magnetic resonance spectroscopy of the internal capsule in human brain: a feasibility study to detect lactate following contralateral motor activity.
Animal experiments suggest that astrocytic glycogen may act as an energy source for axons especially during heightened activity. In this model astrocytic glycogen breaks down to lactate that is shuttled to axons where it is metabolized oxidatively to generate ATP. The aim of this study was to investigate whether (1)H-magnetic resonance spectroscopy could be used to detect a rise in lactate levels in human white matter during enhanced axonal activation. Six healthy volunteers (four women and two men; age range 21-38 years) participated in the study. We were unable to detect any significant MR spectral change, i.e. neither in the peak areas of inositol, choline, creatine, glutamate and N-acetylaspartate nor in the lactate level, in the contralateral posterior limb of the internal capsule during intense motor activation of the hand (four successive episodes of squeezing a soft ball for 7 min followed by 7 min rest). Possible explanations are that the technique is not sensitive enough to detect a small rise in lactate, or lactate turnover is too fast to be detected, or that another monocarboxylate different from lactate may be involved in axonal energy metabolism.
Adenosine Triphosphate↗
Visual stimulation, 1H MR spectroscopy and fMRI of the human visual pathways.
The purpose was to assess changes in lactate content and other brain metabolites under visual stimulation in optical chiasm, optic radiations and occipital cortex using multiple voxel MR spectroscopy (MRS). 1H chemical shift imaging (CSI) examinations of transverse planes centered to include the above structures were performed in four subjects at an echo time of 135 ms. Functional MRI (fMRI) was used to confirm the presence of activity in the visual cortex during the visual stimulation. Spectral maps of optical chiasm were of poor quality due to field disturbances caused by nearby large blood vessels and/or eye movements. The optic radiations and the occipital lobe did not show any significant MR spectral change upon visual stimulation, i.e., the peak areas of inositol, choline, creatine, glutamate and N-acetylaspartate were not affected. Reproducible lactate signals were not observed. fMRI confirmed the presence of strong activations in stimulated visual cortex. Prolonged visual stimulation did not cause significant changes in MR spectra. Any signal observed near the 1.33 ppm resonance frequency of the lactate methyl-group was artifactual, originating from lipid signals from outside the volume of interest (VOI). Previous claims about changes in lactate levels in the visual cortex upon visual stimulation may have been based on such erroneous observations.
Adult↗
Enhanced production and proteolytic degradation of insulin-like growth factor binding protein-2 in proliferating rat astrocytes.
Insulin-like growth factors (IGFs) protect neurons, are important for oligodendrocyte survival and myelin production, and stimulate the proliferation of astrocytes. The effects of IGFs are regulated by a family of IGF binding proteins (IGFBPs). Astrocytes express predominantly IGFBP-2. In the present study, primary neonatal rat astrocytes were cultivated in a chemically defined medium to initiate a differentiated cell status. After stimulation with fetal calf serum, astrocytes became hypertrophic and increased proliferation. Western blot analysis of cell lysate of proliferating astrocytes displayed an increased expression of IGFBP-2. This finding was supported by immunocytochemical images. Semiquantitative polymerase chain reaction analysis demonstrated equal mRNA levels in both differentiated and proliferating astrocytes, suggesting that the increase in IGFBP-2 production in proliferating astrocytes was exerted at the translational level. Concentrated medium of proliferating cells, however, displayed lower levels of IGFBP-2 than differentiated cells. When recombinant IGFBP-2 was incubated with culture media, we found degradation in the medium of proliferating cells, but not in medium of differentiated cells. This degradation could be inhibited with protease inhibitors, indicating that lower levels of IGFBP-2 in the medium of proliferating astrocytes are due to the presence of proteases. Our results suggest that, in proliferating astrocytes, IGFBP-2 may help target IGFs to IGF-1 receptors, and IGFBP-2 proteases may play a role in enhancing the availability of IGFs.
Animals↗
Involvement of insulin-like growth factor binding protein-2 in activated microglia as assessed in post mortem human brain.
In vitro studies suggest that insulin-like growth factor (IGF)-I is a mitogen for microglia/macrophages. The actions of IGF-I are mediated by IGF-I receptors and modulated by IGF binding proteins (IGFBPs). The aim of this study was to investigate IGF-I receptors and IGFBPs in human microglia in normal brain white matter and active lesions of multiple sclerosis, which contain activated microglia/macrophages. Methods used were immunohistochemistry and confocal laser microscopy. IGF-I receptors were demonstrated in both resting and activated microglia. In resting conditions, microglia displayed no immunoreactivity for any of the six IGFBPs, whereas activated microglia/macrophages were immunoreactive for IGFBP-2 only. Our data suggest an important function for IGFBP-2 in IGF-I actions in activated microglia/macrophages in human brain.
Adult↗
Insulin-like growth factor binding protein-1-6 expression in activated microglia.
In the CNS insulin-like growth factor-1 (IGF-1) enhances survival of neurons, promotes myelin synthesis and acts as a mitogen for microglia. The effects of IGF-1 are regulated by a family of 6 IGF binding proteins (IGFBPs). We investigated mRNA expression patterns of IGFBPs in primary rat microglia under basal conditions and after activation with lipopolysaccharide (LPS). Under basal conditions, microglia expressed IGFBP-2 to -6, whereas, IGFBP-1 could not be detected. Following 2 h treatment with LPS mRNA levels for IGFBP-4 and -6 displayed a down regulation, and IGFBP-5 became undetectable. Levels of IGFBP-2 and -3 remained unaltered. Expression patterns of IGFBPs might play an important role in regulating the autocrine/paracrine IGF-1 actions on microglia under inflammatory conditions.
Animals↗
Peripheral blood leukocyte NO production in MS patients with a benign vs progressive course.
BACKGROUND: Nitric oxide (NO) may play a role in tissue destruction and axonal degeneration in multiple sclerosis (MS). OBJECTIVE: To investigate NO production by peripheral blood leukocytes (PBL) in patients with a benign and progressive course of MS. METHODS: PBL were isolated from 25 patients with a benign course of MS (BMS), 33 with secondary progressive MS (SPMS), 21 with primary progressive MS (PPMS), and 29 healthy individuals. Leukocyte supernatants were assayed for nitrite concentration, which is an index of NO generation, using the Griess reaction. Serum levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-12 were measured using ELISA. RESULTS: Compared to healthy controls, nitrite concentrations were higher in patients with BMS (p < 0.001), SPMS (p < 0.001), and PPMS (p < 0.05). There were no significant differences among the three clinical subgroups of MS. There was a correlation between nitrite concentrations and serum levels of IL-12 (p = 0.04), but not of TNFalpha. CONCLUSION: Increased NO production by PBL in patients with MS is independent of the disease course.
Adult↗
Search for morbillivirus proteins in multiple sclerosis brain tissue.
We investigated brain samples of patients with multiple sclerosis (MS) and controls with immunohistochemistry using monoclonal antibodies (MoAbs) against canine distemper virus (CDV) and measles virus (MV) proteins. All stained negative except for MoAb F3-5, which recognises a conserved epitope on the fusion protein of morbilliviruses. F3-5 immunostaining was found in 8/9 MS plaques and 2/5 herpes simplex virus encephalitis brain samples, but not in six controls or four patients with ischaemic stroke. Using RT-PCR we found no evidence for the presence of MV in MS plaques. The F3-5 epitope may represent a protein that is upregulated during inflammation or point to a yet unrecognised morbillivirus in the human central nervous system that might be implicated in MS pathogenesis.
Adult↗
Inheritance mode of multiple sclerosis: the effect of HLA class II alleles is stronger than additive.
We previously identified on chromosome 6 an interval of 51 kb as the most likely interval in the HLA region for a disease-susceptibility locus for multiple sclerosis (MS). The interval was located between markers G511525 and D6S1666 and identified by the haplotype sharing statistic (HSS). The study comprised 124 patients with ancestry within the northeastern part of The Netherlands. Haplotype clustering indicated that two different ancestral haplotypes likely include a polymorphism involved in susceptibility to MS. To investigate the dominance characteristics of the MS susceptibility locus in the HLA class II region, we reanalyzed our data, performing genotype association analyses for both marker loci separately and for the two-locus haplotype. The two-locus genotype association analysis showed that in individuals who carry only one of the risk haplotypes the risk for MS is moderately increased (odds ratio (OR) 2.82; 95% confidence interval (CI) 1.50-5.31). However, in individuals carrying two risk haplotypes the risk for MS is highly increased compared with individuals who carry no risk haplotypes (OR 37.00; 95% CI 8.31-164.74). This susceptibility locus for MS seems to follow an intermediate mode of inheritance. Fitting additive, multiplicative and third power risk models to the data, the effect appears to be significantly stronger than additive.
Alleles↗
Astrocytic beta2-adrenergic receptors and multiple sclerosis.
Despite intensive research, the cause and a cure of multiple sclerosis (MS) have remained elusive and many aspects of the pathogenesis are not understood. Immunohistochemical experiments have shown that astrocytic beta(2)-adrenergic receptors are lost in MS. Because norepinephrine mediates important supportive and protective actions of astrocytes via activation of these beta(2)-adrenergic receptors, we postulate that this abnormality may play a prominent role in the pathogenesis of MS. First, it may allow astrocytes to act as facultative antigen-presenting cells, thereby initiating T-cell mediated inflammatory responses that lead to the characteristic demyelinated lesions. Second, it may contribute to inflammatory injury by stimulating the production of nitric oxide and proinflammatory cytokines, and reducing glutamate uptake. Third, it may lead to apoptosis of oligodendrocytes by reducing the astrocytic production of trophic factors, including neuregulin, nerve growth factor and brain-derived neurotrophic factor. Fourth, it may impair astrocytic glycogenolysis, which supplies energy to axons, and this may represent a mechanism underlying axonal degeneration that is hold responsible for the progressive chronic disability.
Animals↗
Beta 2-adrenoceptor involvement in inflammatory demyelination and axonal degeneration in multiple sclerosis.
Relapses of multiple sclerosis (MS) are considered to be the clinical expression of acute T-cell-mediated inflammatory demyelinating lesions disseminated in the CNS, whereas disease progression seems to result from widespread axonal degeneration. The pathophysiology of both disease components is incompletely understood. Astrocytes in MS lack beta(2)-adrenoceptors, which via cAMP-mediated processes inhibit the expression of major histocompatibility (MHC) class II molecules and stimulate glycogenolysis in normal conditions. In a pro-inflammatory CNS environment this beta(2)-adrenoceptor defect might allow astrocytes to transform into facultative antigen-presenting cells that can initiate the inflammatory cascade. The same receptor defect might impair astrocytic glycogenolysis, which normally generates lactate that is transported to axons as an energy source. Failure of axonal energy metabolism might result in axonal degeneration through mechanisms that involve intra-axonal accumulation of Ca(2+) ions and mitochondrial dysfunction. If this hypothesis is correct, therapies designed to elevate cAMP levels in astrocytes should reduce or prevent both relapses and progression of MS.
Astrocytes↗
Reducing discrepancies between MS patients' needs and use of healthcare services by applying a transmural care model.
The Dutch healthcare system is effective for patients with acute, uncomplicated health problems but ineffective for patients with complex, chronic health problems such as multiple sclerosis (MS). To tackle these deficits, special working parties and the Dutch Ministry of Health concluded that healthcare professionals from primary and hospital settings should, by mutual agreement, cooperation, and shared responsibility, better coordinate their care and tailor care to meet patients' individual needs. In the Netherlands this approach is called transmural care. A transmural care model for MS (TCMMS) was developed to assist healthcare professionals in different settings cooperate with one another, comprehensively assess the needs of MS patients, and define an integrated care plan for each patient. The overall aim of the TCMMS was to reduce the discrepancies between the patients' needs and use of healthcare services and to test whether the TCMMS is applicable in practice. Outcomes using the TCMMS were measured using Kurtzke's Expanded Disability Status Scale (EDSS), Incapacity Status Scale (ISS), Environmental Status Scale (ESS), and RAND 36-Item Health Survey (RAND-36). In the study period, many different expressed needs were reported. For the total group the expressed needs decreased significantly from 57 needs 5 months before the implementation of the TCMMS to 19 needs at the end of the study. There were no significant changes over time in EDSS, ISS, ESS, and RAND-36. Overall, the TCMMS was applicable to practice and decreased the discrepancies between needs and services.
Adult↗
Acetylsalicylic acid and acetaminophen to combat elevated body temperature in acute ischemic stroke.
BACKGROUND: Because elevated body temperature (BT) in acute ischemic stroke is associated with poor outcome, it is currently recommended to maintain normothermia with antipyretics. Whether this can be achieved by the administration of acetylsalicylic acid (ASA) or acetaminophen is uncertain. METHODS: Over a period of 9 months, patients admitted with acute hemiparetic ischemic stroke were monitored for BT in the first 48 h. When BT rose >37.5 degrees C, patients were treated with either ASA 500 mg intravenously or acetaminophen suppository 1,000 mg. When 6 h later the BT was still or again >37.5 degrees C, patients were further treated with acetaminophen suppository 1,000 mg up to 4 times a day. Primary outcome measure was normothermia (BT </=37.5 degrees C) within respectively 1 and 3 h after intervention. Secondary outcome parameters were any decrease in BT and the mean decrease in BT. RESULTS: Of a total of 132 patients, 63 (48%) developed a BT >37.5 degrees C. The effects of 43 injections of ASA and 89 administrations of acetaminophen were studied. After 1 h, treatment with acetaminophen produced both significantly more reductions in BT and normothermia (respectively in 60 and 20%) than treatment with ASA (respectively in 37 and 5%). At 3 h, both interventions had a similar effect, with normothermia being achieved in only 37-38%. Fever (>38.0 degrees C) and evidence of an infection were related to unresponsiveness to treatment. CONCLUSIONS: In the majority of patients with acute ischemic stroke, ASA and acetaminophen are insufficient for reducing an elevated BT to a state of normothermia.
Acetaminophen↗
Free insulin-like growth factor (IGF)-I and IGF binding proteins 2, 5, and 6 in spinal motor neurons in amyotrophic lateral sclerosis.
BACKGROUND: Insulin-like growth factor-I (IGF-I) is a potent survival factor for motor neurons and is being investigated as possible therapeutic agent for amyotrophic lateral sclerosis. However, very little information is available on the components of the IGF-I system in this disease. Insulin-like growth factor binding proteins (IGFBPs) play an important part in regulating the bioavailability of IGF-I. METHODS: We investigated the components of the IGF-I system in spinal cord sections of ten patients with amyotrophic lateral sclerosis and in ten controls without neurological disease. IGF-I was studied by western immunoblotting. IGFBPs and IGF-I receptors were investigated by immunohistochemistry and Western immunoblotting. FINDINGS: Total IGF-I in ventral horn homogenates did not differ between patients and controls. However, free IGF-I was 53% lower in patients than in controls. Compared with controls, immunoreactivity in the spinal motor neurons of patients with amyotrophic lateral sclerosis was 64% higher for IGFBP2, 46% higher for IGFBP5, and 33% higher for IGFBP6, with upregulation of IGF-I receptors. Immunoreactivity for IGFBPs1, 3, and 4 did not differ between patients and controls. INTERPRETATION: In the ventral horns of patients, free IGF-I is reduced, which could be because of specific increases in IGFBPs 2, 5, and 6 in spinal motor neurons. This abnormality might have an important role in the processes leading to motor neuron death, and should be taken into account when developing treatments aimed to stimulate IGF-I receptors in motor neurons.
Aged↗
Are astrocytes central players in the pathophysiology of multiple sclerosis?
An interaction between antimyelin T cells and antigen-presenting glial cells is a crucial step in the cascade of immune events that lead to the inflammatory lesions in multiple sclerosis (MS). One of the most debated and controversial issues is whether microglial cells or astrocytes are the key players in initiating the (auto)immune reactions in the central nervous system in MS. Many investigators consider microglia to be the responsible intrinsic immunoeffector cells. In this review, we speculate that in MS astrocytes may serve as primary (facultative) antigen-presenting cells due to a failure of noradrenergic suppression of class II major histocompatibility complex molecules, which is caused by a loss of beta(2)-adrenergic receptors. If this hypothesis is correct, pharmacologic suppression of the antigen-presenting capacities of astrocytes may be a potential therapy for MS.
Antigen-Presenting Cells↗