Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

<p>Abstract</p> <p>Background</p> <p>The metabolism of amyloid precursor protein (APP) and β-amyloid (Aβ) is widely studied in Alzheimer's disease, where Aβ 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).</p> <p>Methods</p> <p>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 β-amyloid peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor protein (APP) isoforms α-sAPP and β-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.</p> <p>Results</p> <p>In the cross-sectional study, LNB patients had lower levels of CSF α-sAPP, β-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 α-sAPP, β-sAPP and P-tau at baseline, which all increased towards normal at follow-up.</p> <p>Conclusions</p> <p>Amyloid metabolism is altered in LNB. CSF levels of α-sAPP, β-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.</p

Association between thyroid hormone levels and monoaminergic neurotransmission during surgery

Background: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. Methods: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3 h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. Results: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T-3/T-4 ratio (rho = 0.41, p = 0.017). During surgery, serum thyroid hormones and the T-3/T-4 ratio decreased (p < 0.0001), while the CSF T-3/T-4 ratio increased (p = 0.0009). There were no correlations between serum and CSF levels of T-3 and T-4 at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. Conclusions: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress

Changes in serum and cerebrospinal fluid cytokines in response to non-neurological surgery: an observational study

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

Neurobiological markers for personality, inflammation and stress: A naturalistic study in knee arthroplastic patients

Background: Psychiatry has strived to identify biomarkers elucidating the underlying biological mechanisms behind different disorders, to help in diagnostics and to assess treatment effects. In forensic psychiatric populations, findings have connected levels of cerebrospinal fluid (CSF) monoamine metabolites and blood-brain barrier (BBB) integrity with impulsivity and aggression. Other biomarkers, like insulin, inflammatory mediators, and different markers for neuronal and astroglial integrity have been studied in connection with cognition and psychiatric disorders but to a lesser degree in relationship to personality traits. Aim: The overall aims were to establish links between CSF markers for monoamine activity, BBB integrity, hormones, inflammation and neuronal and astroglial integrity, and aggressive and impulsive personality traits in a population group of persons without psychiatric disorders, and to describe the distribution and dynamics of new biomarkers. Methods: Serum and CSF samples were collected before, three hours after, and on the morning following arthroplastic knee surgery in 35 patients who had completed two personality questionnaires, the Temperament and Character Inventory (TCI) and the Karolinska Scales of Personality (KSP). Results: The CSF Homovanillic AcidHVA/5-hydroxyindoleacetic Acid 5-HIAA ratio correlated negatively with Cooperativeness. Beta-trace protein, as a marker of BBB dysfunction, correlated positively with Monotony Avoidance and Impulsiveness. Positive correlations were observed between CSF interleukin (IL)-10 and Verbal Aggression and between Self-directedness, serum IL-10, and interferon-γ. CSF IL-10 correlated negatively with Inhibited Aggression, and CSF cortisol with Novelty Seeking. No correlations were detected between aggressive and impulsive personality traits and CSF levels of insulin, thyroid hormone, astroglial or neuronal integrity markers, or CSF/serum albumin ratio. Levels of CSF cytokines were markedly increased during and after the intervention compared to serum. Insulin levels in the brain seemed to be regulated differently from in the periphery, and modest increases in total Tau were observed during surgery. Conclusion: Some aggressive and impulsive personality traits in non-disordered persons co-vary with various CSF biomarkers indicating lack of serotonergic control over dopamine signaling, decreased BBB integrity and inflammation

Cerebrospinal fluid insulin during non-neurological surgery

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