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 ◽  
...  

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.

1986 ◽  
Vol 71 (6) ◽  
pp. 749-753 ◽  
Author(s):  
J. E. Maddison ◽  
D. Yau ◽  
P. Stewart ◽  
G. C. Farrell

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.


2008 ◽  
Vol 25 (10) ◽  
pp. 2243-2249 ◽  
Author(s):  
Rie Sakae ◽  
Atsuko Ishikawa ◽  
Tomoko Niso ◽  
Yukiko Komori ◽  
Tetsuya Aiba ◽  
...  

2015 ◽  
Vol 8 ◽  
pp. IJTR.S25915 ◽  
Author(s):  
Markus K. Larsson ◽  
Lilly Schwieler ◽  
Michel Goiny ◽  
Sophie Erhardt ◽  
Göran Engberg

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.


PEDIATRICS ◽  
1980 ◽  
Vol 65 (1) ◽  
pp. 115-120
Author(s):  
Kirti Upadhyaya ◽  
Kenneth Barwick ◽  
Mark Fishaut ◽  
Michael Kashgarian ◽  
Norman J. Siegel

Fifteen children with the clinical manifestations of hemolytic-uremic syndrome are reported.Prompt recognition of the syndrome and effective therapy for acute renal failure including early dialysis were institured in each case. Analysis of the clinical course and histopathologic features in these patients indicated that early dialysis and effective management of acute renal failure may unmask evidence of nonrenal involvement; microthrombi may be found in a wide distribution of organs, including the brain and myocardium; and extent and severity of nonrenal involvement become an important determinant of ultimate prognosis.


1997 ◽  
Vol 20 (8) ◽  
pp. 939-942 ◽  
Author(s):  
Mami HAGINO ◽  
Koujirou YAMAMOTO ◽  
Kiyoko OHASHI ◽  
Tomoko SUEDA ◽  
Hajime KOTAKI ◽  
...  

1965 ◽  
Vol 20 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Walter B. Essman

Five groups of male rats were trained to a criterion of correct responses in a T-maze. Each group of animals was then subjected to one of five techniques for production of acute renal failure: nephrectomy, sham operation, methemoglobin-sodium ferrocyanide-injection leading to nonazotemia, methemoglobin-sodium ferrocyanide-injection resulting in azotemia, and saline injection. All animals were given trials in the maze spaced at 6-hr. intervals Response latencies and error scores suggested behavioral changes for the injected-azotemic animals and the nephrectomized animals. Qualitative as well as quantitative behavioral differences emerged as a function of the method utilized to produce acute renal failure.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ekaterina Martynova ◽  
Mehendi Goyal ◽  
Shikhar Johri ◽  
Vinay Kumar ◽  
Timur Khaibullin ◽  
...  

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.


1985 ◽  
Vol 104 (3) ◽  
pp. 325-330 ◽  
Author(s):  
D. H. Abbott ◽  
K. A. Batty ◽  
A. K. Dubey ◽  
J. Herbert ◽  
H. M. Shiers

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


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