Cerebrospinal fluid dynamics modulation by diet and cytokines in rats

Autor: A. Jane Loughlin, Jane E. Preston, Ester Pascual-Baixauli, Zerin Alimajstorovic, Basil Sharrack, Cheryl A. Hawkes, Ignacio A. Romero
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Necrosis
Intracranial Pressure
lcsh:RC346-429
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Cerebrospinal fluid
Developmental Neuroscience
Internal medicine
Medicine
Animals
Ketamine
Obesity
Rats
Wistar
lcsh:Neurology. Diseases of the nervous system
Hydrocortisone
Cerebrospinal Fluid
Cerebrospinal Fluid Leak
Ventriculo-cisternal perfusion
business.industry
Research
Interleukin
Brain
Raised intracranial pressure
General Medicine
Diet
Idiopathic intracranial hypertension
030104 developmental biology
Endocrinology
Neurology
Variable rate infusion
Hydrodynamics
Cytokines
Choroid plexus
Female
medicine.symptom
Intracranial Hypertension
business
Perfusion
030217 neurology & neurosurgery
Glucocorticoid
medicine.drug
Zdroj: Fluids and Barriers of the CNS, Vol 17, Iss 1, Pp 1-10 (2020)
Fluids and Barriers of the CNS
ISSN: 2045-8118
Popis: Background Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. Methods In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C–C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). Results Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/μl controls, and 7.09 ± 0.26 mmH2O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. Conclusions Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.
Databáze: OpenAIRE
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