scholarly journals Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

2015 ◽  
Vol 8 ◽  
pp. IJTR.S25915 ◽  
Author(s):  
Markus K. Larsson ◽  
Lilly Schwieler ◽  
Michel Goiny ◽  
Sophie Erhardt ◽  
Göran Engberg
Keyword(s):  
Cerebrospinal Fluid ◽  
Kynurenic Acid ◽  
Chronic Treatment ◽  
Antipsychotic Drugs ◽  
Interleukin 8 ◽  
Antipsychotic Treatment ◽  
Brain Levels ◽  
Immunosuppressive Action ◽  
Csf Levels ◽  
The Brain

Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline ( n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.

Cerebrospinal fluid γ-aminobutyric acid levels in dogs with chronic portosystemic encephalopathy

1986 ◽  
Vol 71 (6) ◽  
pp. 749-753 ◽  
Author(s):  
J. E. Maddison ◽  
D. Yau ◽  
P. Stewart ◽  
G. C. Farrell
Keyword(s):  
Cerebrospinal Fluid ◽  
Aminobutyric Acid ◽  
Plasma Ammonia ◽  
Portosystemic Encephalopathy ◽  
Dog Model ◽  
Csf Levels ◽  
Neurological Features ◽  
The Brain ◽  
Biochemical Abnormalities

1. Cerebrospinal fluid (CSF) γ-aminobutyric acid (GABA) levels were measured in a dog model of spontaneous chronic portosystemic encephalopathy. 2. Dogs with congenital portacaval shunts (intra- or extra-hepatic) develop neurological features of abnormal psychomotor behaviour and depressed consciousness that are consistent with the symptoms of chronic portosystemic encephalopathy in humans. In the five dogs studied, plasma ammonia was elevated, as was CSF tryptophan, both usual biochemical abnormalities in portosystemic encephalopathy. 3. CSF levels of GABA in five dogs with portosystemic encephalopathy (100 ± 13 pmol/ml) were not significantly different from those in five control dogs (96 ± 14 pmol/ml). CSF levels of GABA were not altered after ammonia infusion. 4. If enhanced GABA-ergic neurotransmission, due to influx of gut-derived GABA into the brain, is responsible for the pathophysiology of chronic portosystemic encephalopathy in this model, it is not reflected by increased levels of GABA in CSF.

Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment

2015 ◽  
Vol 43 ◽  
pp. 198-204 ◽  
Author(s):  
Anniella Isgren ◽  
Joel Jakobsson ◽  
Erik Pålsson ◽  
Carl Johan Ekman ◽  
Anette G.M. Johansson ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cerebrospinal Fluid ◽  
Interleukin 8 ◽  
Antipsychotic Treatment

scholarly journals Accumulation of uremic solutes in the cerebrospinal fluid in experimental acute renal failure

2019 ◽  
Vol 317 (2) ◽  
pp. F296-F302 ◽  
Author(s):  
Robert DeWolfe Mair ◽  
Huy Nguyen ◽  
Ting-Ting Huang ◽  
Natalie S. Plummer ◽  
Tammy L. Sirich ◽  
...  
Keyword(s):  
Renal Failure ◽  
Cerebrospinal Fluid ◽  
Acute Renal Failure ◽  
Great Majority ◽  
Sham Operation ◽  
Csf Levels ◽  
Operation Control ◽  
Uremic Solutes ◽  
The Brain ◽  
Plasma Ultrafiltrate

The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; n = 10) or bilateral nephrectomy ( n = 10) and analyzed using an established metabolomic platform. Two hundred forty-eight solutes were identified as uremic based on their accumulation in the plasma ultrafiltrate of nephrectomized compared with control rats. CSF levels of 124 of these solutes were sufficient to allow calculation of CSF-to-plasma ultrafiltrate concentration ratios. Levels of many of the uremic solutes were normally lower in the CSF than in the plasma ultrafiltrate, indicating exclusion of these solutes from the brain. CSF levels of the great majority of the uremic solutes increased in renal failure. The increase in the CSF was, however, relatively less than in the plasma ultrafiltrate for most solutes. In particular, for the 31 uremic solutes with CSF-to-plasma ultrafiltrate ratios of <0.25 in control rats, the average CSF-to-plasma ultrafiltrate ratio decreased from 0.13 ± 0.07 in control rats to 0.09 ± 0.06 in nephrectomized rats, revealing sustained ability to exclude these solutes from the brain. In summary, levels of many uremic solutes are normally kept lower in the CSF than in the plasma ultrafiltrate by the action of the blood-brain and blood-CSF barriers. These barriers remain functional but cannot prevent accumulation of uremic solutes in the CSF when the kidneys fail.

Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings

2009 ◽  
Vol 39 (11) ◽  
pp. 1763-1777 ◽  
Author(s):  
S. Navari ◽  
P. Dazzan
Keyword(s):  
Brain Structure ◽  
Structural Changes ◽  
Antipsychotic Drugs ◽  
Brain Magnetic Resonance Imaging ◽  
Specific Effect ◽  
Future Research ◽  
Antipsychotic Treatment ◽  
Mri Findings ◽  
Brain Volumes ◽  
The Brain

BackgroundThe potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type?MethodA systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: ‘antipsychotics’ AND ‘brain’ AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed.ResultsThirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal.ConclusionsAntipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

scholarly journals Imbalanced Kynurenine Pathway in Schizophrenia

2014 ◽  
Vol 7 ◽  
pp. IJTR.S16800 ◽  
Author(s):  
Magdalena E. Kegel ◽  
Maria Bhat ◽  
Elisabeth Skogh ◽  
Martin Samuelsson ◽  
Kristina Lundberg ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Kynurenine Pathway ◽  
The Other ◽  
Healthy Controls ◽  
Liquid Chromatography Mass Spectrometry ◽  
Csf Levels

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

scholarly journals Serum and Cerebrospinal Fluid Cytokine Biomarkers for Diagnosis of Multiple Sclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ekaterina Martynova ◽  
Mehendi Goyal ◽  
Shikhar Johri ◽  
Vinay Kumar ◽  
Timur Khaibullin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Pearson Correlation ◽  
Relapsing Remitting ◽  
Diagnosis And Classification ◽  
Diagnosis Accuracy ◽  
Csf Levels ◽  
Ifn Γ ◽  
The Brain ◽  
Ms Pathogenesis

Background. Multiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF). Objective. Serum and CSF levels of forty-five cytokines were analyzed to identify MS diagnostic markers. Methods. Cytokines were analyzed using multiplex immunoassay. ANOVA-based feature and Pearson correlation coefficient scores were calculated to select the features which were used as input by machine learning models, to predict and classify MS. Results. Twenty-two and twenty cytokines were altered in CSF and serum, respectively. The MS diagnosis accuracy was ≥92% when any randomly selected five of these biomarkers were used. Interestingly, the highest accuracy (99%) of MS diagnosis was demonstrated when CCL27, IFN-γ, and IL-4 were part of the five selected cytokines, suggesting their important role in MS pathogenesis. Also, these binary classifier models had the accuracy in the range of 70-78% (serum) and 60-69% (CSF) to discriminate between the progressive (primary and secondary progressive) and relapsing-remitting forms of MS. Conclusion. We identified the set of cytokines from the serum and CSF that could be used for the MS diagnosis and classification.

The passage of 5α-dihydrotestosterone from serum into cerebrospinal fluid and LH negative feedback in castrated rhesus monkeys

1985 ◽  
Vol 104 (3) ◽  
pp. 325-330 ◽  
Author(s):  
D. H. Abbott ◽  
K. A. Batty ◽  
A. K. Dubey ◽  
J. Herbert ◽  
H. M. Shiers
Keyword(s):  
Cerebrospinal Fluid ◽  
Rhesus Monkeys ◽  
Serum Levels ◽  
Blood Levels ◽  
Lipid Solubility ◽  
Total Blood ◽  
Serum Lh ◽  
Csf Levels ◽  
The Brain ◽  
Vascular Compartment

ABSTRACT Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0·3–0·6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5α-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l and, even more obviously, if unbound DHT decreased to less than about 2 nmol/l. Differences between the distribution of testosterone and DHT between blood and CSF cannot be explained by serum binding, lipid solubility or clearance from the brain, and suggest that there may be some mechanism for excluding DHT from the CSF. Though DHT reaches the CSF from the blood in small amounts, levels there do not relate predictably to those in the vascular compartment. It seems unlikely, therefore, that levels of intracerebral DHT are controlled by changes in those of the blood. J. Endocr. (1985) 104, 325–330

scholarly journals The Pharmacodynamics of Antipsychotic Drugs in Women and Men

2021 ◽  
Vol 12 ◽  
Author(s):  
Mary V. Seeman
Keyword(s):  
Adverse Effects ◽  
Drug Response ◽  
Antipsychotic Drugs ◽  
Psychotic Symptoms ◽  
Antipsychotic Treatment ◽  
Hepatic Enzymes ◽  
Biological Sex ◽  
Search Terms ◽  
Human Experiments ◽  
The Brain

Background: Animal and human experiments have confirmed sex differences in the expression of hepatic enzymes that metabolize antipsychotic drugs and that may, in this way, be partly responsible for the clinical sex/gender differences observed in the efficacy and tolerability of antipsychotic treatment.Aim: The aim of this mini review is to synthesize the literature on the pharmacodynamics of male/female differential response to antipsychotic drugs.Method: Relevant search terms were used to search for pre-clinical and human trials and analysis of antipsychotic differential drug response and occurrence/severity of adverse effects in women and men.Results: The search found that sex influences drug response via the amount of a given drug that enters the brain and the number of neurotransmitter receptors to which it can bind. Consequently, sex partly determines the efficacy of a specific drug and its liability to induce unwanted effects. There are other factors that can overshadow or enhance the dimorphic effect of sex, for instance, the host's age, hormonal status, diet and life style as well as the molecular structure of the drug and its dose, and the method of its administration. Most of all, the host's individual genetics affects each step of a drug's pharmacodynamics.Conclusion: On average, women's psychotic symptoms respond to antipsychotic drugs at doses lower than men's. This means that many women may be de facto overdosed and, thus, experience unnecessary adverse effects. That being said, factors such as genetics and age probably determine drug response and tolerability to a greater degree than do biological sex or gender social roles.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

Vasopressin enhances the clearance of β-endorphin immunoreactivity from rat cerebrospinal fluid

1990 ◽  
Vol 122 (2) ◽  
pp. 191-200 ◽  
Author(s):  
C. G. J. Sweep ◽  
Margreet D. Boomkamp ◽  
István Barna ◽  
A. Willeke Logtenberg ◽  
Victor M. Wiegant
Keyword(s):  
Cerebrospinal Fluid ◽  
Receptor Antagonist ◽  
Short Duration ◽  
Lateral Ventricle ◽  
Underlying Mechanism ◽  
Terminal Phase ◽  
Intracerebroventricular Injection ◽  
Intracerebroventricular Administration ◽  
Biphasic Pattern ◽  
The Brain

Abstract The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of β-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4–9) (1.44 fmol), Nα-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of β-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1–9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied β-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel β-endorphin-(1–31), the β-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lifes of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol β-endorphin-(1–31)) significantly enhanced the disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of β-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.

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