scholarly journals Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Nadine Striepens ◽  
Keith M. Kendrick ◽  
Vanessa Hanking ◽  
Rainer Landgraf ◽  
Ullrich Wüllner ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intranasal Administration ◽  
Blood Concentrations

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

Lethal morphine intoxication in a patient with a sickle cell crisis and renal impairment: Case report and a review of the literature

2010 ◽  
Vol 30 (9) ◽  
pp. 1399-1403 ◽  
Author(s):  
Jurjen S Lagas ◽  
Jiri FP Wagenaar ◽  
Alwin DR Huitema ◽  
Michel JX Hillebrand ◽  
Cornelis HW Koks ◽  
...  
Keyword(s):  
Renal Failure ◽  
Cerebrospinal Fluid ◽  
Renal Impairment ◽  
Sickle Cell ◽  
Plasma Concentrations ◽  
Fatal Outcome ◽  
High Plasma ◽  
Blood Concentrations ◽  
Morphine Administration ◽  
Central Nervous System Penetration

Morphine-6-glucuronide, the active metabolite of morphine, and to a lesser extent morphine itself are known to accumulate in patients with renal failure. A number of cases on non-lethal morphine toxicity in patients with renal impairment report high plasma concentrations of morphine-6-glucuronide, suggesting that this metabolite achieves sufficiently high brain concentrations to cause long-lasting respiratory depression, despite its poor central nervous system penetration. We report a lethal morphine intoxication in a 61-year-old man with sickle cell disease and renal impairment, and we measured concentrations of morphine and morphine-6-glucuronide in blood, brain and cerebrospinal fluid. There were no measurable concentrations of morphine-6-glucuronide in cerebrospinal fluid or brain tissue, despite high blood concentrations. In contrast, the relatively high morphine concentration in the brain suggests that morphine itself was responsible for the cardiorespiratory arrest in this patient. Given the fatal outcome, we recommend to avoid repeated or continuous morphine administration in renal failure.

Cerebrospinal fluid and blood concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following castration of adult male rats

1992 ◽  
Vol 127 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Nafisa Balasinor ◽  
Manjit K Gill-Sharma ◽  
Priyanka Parte ◽  
HS Juneja
Keyword(s):  
Cerebrospinal Fluid ◽  
Adult Male ◽  
Systemic Circulation ◽  
Male Rats ◽  
Sham Operation ◽  
Turnover Rates ◽  
Blood Concentrations ◽  
Serum Lh ◽  
Norepinephrine Turnover ◽  
Hypothalamic Dopamine

Comparative levels of LH, FSH and PRL in the serum and cerebrospinal fluid (CSF) of adult male rats were studied at different periods following castration. Intact and sham-operated animals served as controls. Blood and CSF were collected at 1, 3, 7, 14, 21, 28, 35 and 46 days following castration. The CSF was collected via cisterna-magna puncture, while the blood was collected from abdominal aorta. Serum gonadotropins increased progressively beginning day 1 post-castration to reach maximum by day 35 or 46 post-castration. Sham operation and castration did not affect mean CSF, LH and FSH levels compared to intact controls. Analysis of the temporal pattern of serum and CSF gonadotropin levels following castration revealed significant positive correlation between CSF and serum LH (r=0.58) and FSH (r=0.64) levels respectively. The data suggest that CSF gonadotropins may be derived from systemic circulation. Serum PRL levels were not affected by castration, but CSF PRL levels were significantly reduced at days 28, 35 and 46 post-castration compared to intact controls. CSF PRL levels showed negative correlation with serum LH and FSH levels but failed to show a correlation with serum PRL levels. Hypothalamic norepinephrine turnover rate increased at days 28, 35 and 46 post-castration. Hypothalamic dopamine contents and turnover rates were reduced at days 21 and 28 post-castration. It is suggested that CSF PRL may have a role in the regulation of serum gonadotropins.

Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after intranasal administration

2008 ◽  
Vol 60 (9) ◽  
pp. 1149-1154 ◽  
Author(s):  
Yan Zhao ◽  
Tao Tao ◽  
Jinjin Wu ◽  
Jiaxin Pi ◽  
Ning He ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intranasal Administration ◽  
Rat Plasma

scholarly journals Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis

Cephalalgia ◽  
2016 ◽  
Vol 37 (1) ◽  
pp. 49-63 ◽  
Author(s):  
Robin M van Dongen ◽  
Ronald Zielman ◽  
Marek Noga ◽  
Olaf M Dekkers ◽  
Thomas Hankemeier ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Meta Analysis ◽  
Episodic Migraine ◽  
Future Research ◽  
Csf Biomarkers ◽  
Blood Concentrations ◽  
Biochemical Compounds ◽  
Calcitonin Gene ◽  
Mean Differences ◽  
Episodic Migraineurs

Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: –1.37, 95% CI: –1.80, –0.94) and interictal episodic migraine patients (three studies, SMD: –1.12, 95% CI: –1.65, –0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

scholarly journals Kinetic Profile of the Transcriptome Changes Induced in the Choroid Plexus by Peripheral Inflammation

2009 ◽  
Vol 29 (5) ◽  
pp. 921-932 ◽  
Author(s):  
Fernanda Marques ◽  
João C Sousa ◽  
Giovanni Coppola ◽  
Ana M Falcao ◽  
Ana João Rodrigues ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Brain Parenchyma ◽  
Matrix Remodeling ◽  
Choroid Plexus Epithelial Cell ◽  
Blood Concentrations ◽  
The Brain

The choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specific to a restricted number of genes (out of a total of 24,000 genes analyzed, 252 are up-regulated and 173 are down-regulated) and transient, as it returns to basal conditions within 72 h. The up-regulated genes cluster into families implicated in immune-mediated cascades and in extracellular matrix remodeling, whereas those down-regulated participate in maintenance of the barrier function. Importantly, several acute-phase proteins, whose blood concentrations rise in response to inflammation, may contribute to the effects observed in vivo after LPS injection, as suggested by the differential response of primary choroid plexus epithelial cell cultures to LPS alone or to serum collected from animals exposed to LPS. By modulating the composition of the cerebrospinal fluid, which will ultimately influence the brain parenchyma, the choroid plexus response to inflammation may be of relevance in brain homeostasis in health and disease.

Blood–cerebrospinal fluid barrier to arginine-vasopressin, desmopressin and desglycinamide arginine-vasopressin in the dog

1982 ◽  
Vol 93 (3) ◽  
pp. 319-325 ◽  
Author(s):  
V. T. Y. Ang ◽  
J. S. Jenkins
Keyword(s):  
Cerebrospinal Fluid ◽  
Intravenous Injection ◽  
Arginine Vasopressin ◽  
Half Life ◽  
Intranasal Administration ◽  
Route Of Administration ◽  
Total Plasma ◽  
Intranasal Route ◽  
Plasma Half Life

The passage of 125I-labelled arginine-vasopressin (AVP) and its analogues desmopressin (DDAVP) and desglycinamide arginine-vasopressin (DGAVP) into cerebrospinal fluid (CSF) has been studied in the dog. After intravenous injection or infusion of these peptides radioactive sustances were found in the CSF in amounts ranging from 0·5 to 1·4% of the total plasma radioactivity. However, only DDAVP could be identified in the CSF as the unmetabolized peptide. This observation may be related to the long plasma half-life of DDAVP which was found to be 50 min, compared with a half-life of 13 min for AVP and 8 min for DGAVP. After the intranasal administration of either [3H]AVP or 125I-labelled AVP similar results were obtained. Radioactivity was again present in the CSF but no AVP could be identified. These observations showed that the intranasal route of administration provides no increased access to the CSF. The existence of a blood–CSF barrier to AVP is confirmed and indicates that the concentrations of the hormone normally found in CSF arise from sources other than the blood.

Cerebrospinal Fluid and Blood CX3CL1 as a Potential Biomarker in Early Diagnosis and Prognosis of Dementia

2020 ◽  
Vol 17 (8) ◽  
pp. 709-721
Author(s):  
Agnieszka Kulczyńska-Przybik ◽  
Agnieszka Słowik ◽  
Piotr Mroczko ◽  
Bartłomiej Borawski ◽  
Magdalena Groblewska ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Early Diagnosis ◽  
Crucial Role ◽  
Causative Factor ◽  
Older Individuals ◽  
Blood Concentrations ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker

Background: A growing body of evidence highlights the crucial role of neuroinflammation and chemokine involvement in cognitive impairment pathophysiology. Fractalkine (CX3CL1) appears to be a relevant causative factor in the development of dementia, particularly at the early stages of the disease. However, limited data are available on the levels of CX3CL1 in the cerebrospinal fluid (CSF) and blood. Additionally, to date, its utility as a biomarker for MCI or AD has not been studied. Objective: The aim of the present study was to evaluate the clinical utility of CX3CL1 in the early diagnosis of cognitive impairment. We also compared the diagnostic usefulness of CX3CL1 with other biomarkers associated with neuroinflammation. Methods: A total of 60 patients with cognitive impairment, including 42 patients with AD and 18 subjects with MCI, as well as 20 cognitively healthy controls were enrolled in the study. CSF and blood concentrations of CX3CL1, CCL-2, and YKL-40 were measured by ELISA. Results: Significantly higher CSF and blood concentrations of CX3CL1 were observed in MCI and AD patients compared to older individuals without cognitive impairment. The increase in the levels of CX3CL1 and YKL-40 in non-demented subjects was associated with MCI. The area under the ROC curve for CX3CL1 in MCI subjects was larger in comparison to classical AD markers. Conclusion: Presented results indicate a crucial role of CX3CL1 in the pathology of cognitive impairment and the potential usefulness of this protein in the early diagnosis of MCI and AD.

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