| 1. |
- Anckarsäter, Rolf, 1956, et al.
(författare)
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Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity.
- 2014
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 121:6, s. 649-653
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Tidskriftsartikel (refereegranskat)abstract
- Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid β (Aβ42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p=0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aβ42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.
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| 2. |
- Bjerke, Maria, 1977, et al.
(författare)
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Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
- 2010
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
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| 3. |
- Bromander, Sara, et al.
(författare)
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Cerebrospinal fluid insulin during non-neurological surgery.
- 2010
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Ingår i: J Neural Transm (Vienna, Austria:1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 20, s. 328-329
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Tidskriftsartikel (refereegranskat)abstract
- Insulin plays an important metabolic and transmitter role in the central nervous system, but few studies have investigated the relationship between central and peripheral insulin concentrations. 35 patients undergoing knee surgery had cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning following surgery. Serum insulin concentrations increased after surgery and CSF insulin concentrations changed in the same direction with far smaller amplitude. These results indicate that the blood-brain barrier protects the brain from stress-induced peripheral hormonal fluctuations.
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| 4. |
- Bromander, Sara, et al.
(författare)
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Changes in serum and cerebrospinal fluid cytokines in response to non-neurological surgery: an observational study.
- 2012
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Ingår i: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Background: Surgery launches an inflammatory reaction in the body, as seen through increased peripheral levels of cytokines and cortisol. However, less is known about perioperative inflammatory changes in the central nervous system (CNS). Our aim was to compare inflammatory markers in serum and cerebrospinal fluid (CSF) before and after surgery and evaluate their association with measures of blood–brain barrier (BBB) integrity. Methods: Thirty-five patients undergoing knee arthroplastic surgery with spinal anesthesia had CSF and serum samples drawn before, after and on the morning following surgery. Cytokines and albumin in serum and CSF and cortisol in CSF were assessed at all three points. Results: Cytokines and cortisol were significantly increased in serum and CSF after surgery (Ps <0.01) and CSF increases were greater than in serum. Ten individuals had an increased cytokine response and significantly higher CSF/serum albumin ratios (Ps <0.01), five of whom had albumin ratios in the pathological range (>11.8). Serum and CSF levels of cytokines were unrelated, but there were strong correlations between CSF IL-2, IL-10 and IL-13, and albumin ratios (Ps <0.05) following surgery. Conclusion: Cytokine increases in the CNS were substantially greater than in serum, indicating that the CNS inflammatory system is activated during peripheral surgery and may be regulated separately from that in the peripheral body. CSF cytokine increase may indicate sensitivity to trauma and is linked to BBB macromolecular permeability.
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| 5. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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| 6. |
- Hesse, Camilla, et al.
(författare)
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The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499
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Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
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| 7. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism.
- 2010
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 10:51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The metabolism of amyloid precursor protein (APP) and beta-amyloid (Abeta) is widely studied in Alzheimer's disease, where Abeta deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB). METHODS: The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the beta-amyloid peptides Abeta38, Abeta40 and Abeta42, and the amyloid precursor protein (APP) isoforms alpha-sAPP and beta-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers. RESULTS: In the cross-sectional study, LNB patients had lower levels of CSF alpha-sAPP, beta-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up. CONCLUSIONS: Amyloid metabolism is altered in LNB. CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.
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| 8. |
- Nilsson, Thomas, 1954, et al.
(författare)
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Neurochemical measures co-vary with personality traits: Forensic psychiatric findings replicated in a general population sample
- 2010
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 178:3, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- Neurobiological markers in cerebrospinal fluid (CSF) and in serum, previously found to co-vary with destructive personality traits in violent offenders, were explored in a general population sample of 21 patients undergoing knee surgery. Results on the Karolinska Scales of Personality (KSP) and the Temperament and Character Inventory (TCI) were compared with CSF/serum albumin ratios and serum concentrations of beta-trace protein (beta TP) (as markers for blood-brain barrier (BBB) permeability), to CSF/serum albumin ratios between the dopamine and serotonin metabolites homovanillic acid (HVA)/5-hydroxyindoleacetic acid (HIM) and to CSF and serum ratios between activated thyroid hormone (T3) and its precursor T4. Serum beta TP concentrations correlated with CSF/serum albumin ratios (P=0.018), but not with preoperative serum creatinine concentrations. Serum beta TP correlated significantly with Monotony Avoidance and Impulsiveness: CSF HVA/5-HIAA ratios with Irritability and low Cooperativeness. The beta TP is a potential serum marker for the integrity of the BBB that does not necessitate lumbar puncture. Thyroid hormones did not correlate with personality traits. As reported in forensic psychiatric patients, aggressive, unempathic personality traits were thus associated with increased dopaminergic activity in relation to the serotonergic activity and impulsivity to increased BBB permeability also in a general population group. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 9. |
- Anckarsäter, Rolf, 1956
(författare)
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Neurochemical and neuroendocrine reactions during non-neurological surgery
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Objective: To study changes in serum and cerebrospinal fluid (CSF) proteins, monoamine metabolites and hormones during non-neurological surgery. Subjects and methods: Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, three hours after and on the morning after surgery. Results: The CSF/serum albumin ratios decreased significantly during the study period, especially after the interventions. In contrast, CSF concentrations of beta-2-microglobulin (β2M) increased significantly during surgery and remained high. The CSF concentrations of beta-trace protein (βTP) remained unchanged. The dopamine metabolite homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) increased sharply in the CSF during surgery and reached 188% and 166% of their initial concentrations on the morning after the intervention. The CSF concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglucol (MHPG) increased modestly (non-significantly) during and after surgery. The HVA/5-HIAA ratios initially increased but returned almost to their initial level during the night after surgery. During and after surgery, serum thyroid hormones and the T3/T4 ratio decreased, while the CSF T3/T4 ratio instead increased. At baseline, the CSF MHPG concentrations were significantly correlated to the serum T3/T4 ratios. The base-line CSF thyroid hormones were strongly correlated with the subsequent changes in monoamine metabolite concentrations during and after surgery. Serum insulin concentrations first decreased modestly but then increased sharply after surgery with a wide interpersonal variation, while the CSF insulin concentrations changed in the same directions, albeit with smaller amplitudes. Due to the increase in serum insulin, the CSF/serum insulin ratios decreased. Conclusions: Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity. There was a strong increase in serotonergic and dopaminergic neurotransmission during surgery, with a comparatively stable relationship between the metabolites from these systems. Changes in thyroid hormone and insulin metabolism during surgery are not similar peripherally and in the central nervous system. Thyroid hormone activity may influence brain monoaminergic neurotransmission. No correlations between the CSF/serum ratios of albumin, βTP, insulin and T4 were found, consistent with separate transport mechanisms from the blood into the CSF for these substances in humans in vivo. Key-words: albumin, beta-2-microglobuline, blood brain barrier, cerebrospinal fluid, inflammation, spinal anesthesia, stress
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