Obesity and sex hormones interact to promote CSF hyperdynamics in an obese rodent model of idiopathic intracranial hypertension
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PROVIDER: PRJNA974018 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contributions of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved. We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics. Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Chronic adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to the elevated CSF drainage capacity of these rats. Obesity in itself therefore does not suffice to recapitulate the IIH symptoms, but modulation of CSF dynamics comes about with adjuvant testosterone treatment, mimicking the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus play a crucial role in the disease mechanism of IIH.
2024-01-31 | GSE232814 | GEO
Project description:The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. Speculations regarding the role of cerebrospinal fluid (CSF) protein biomarkers in understanding the pathomechanism of IIH needs to be studied using the high-throughput omics approaches.In this study we have performed an untargeted SWATH-MS proteomics approach to identify CSF biomarkers in IIH cases compared to control subjects.
2023-10-24 | PXD027751 | Pride
Project description:Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11?-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH.
| S-EPMC4847593 | biostudies-literature
Project description:We examined the transcriptional profile of subcutaneous adipose tissue in Idiopathic intracranial hypertension (IIH) patients compared to a control cohort matched for gender and BMI
2021-04-20 | GSE171398 | GEO
Project description:Gene expression information is useful in prioritizing candidate genes in linkage intervals. The data can also identify pathways involved in the pathophysiology of disease. We used microarrays to identify which genes are expressed in either intracranial arteries (control) or in intracranial aneurysms (case), and can therefore contribute to the disease phenotypes. We used microarrays to identify the pathway membership of expressed genes and the overrepresentation of pathways with expressed genes in the known linkage intervals for intracranial aneurysms. Keywords: Characterization of expression in both diseased and non-diseased intracranial arteries.
2007-11-20 | GSE6551 | GEO
Project description:Based on sequencing technology to evaluate the differential lncRNA and mRNA expression of intracranial aneurysms. Provide ideas for the study of epigenetic regulation of intracranial aneurysms
2020-09-26 | GSE158558 | GEO
Project description:BackgroundImpaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.MethodsNfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.ResultsCSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.ConclusionsThe observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.
| S-EPMC9832777 | biostudies-literature
Project description:Intracranial aneurysm sequencing data
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Project description:Intracranial aneurysm is a cerebrovascular disorder in which degeneration of intima and internal elastic lamina of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel. Different molecular mechanisms are involved in sIA formation in patients. We used microarrays to detail the gene expression of intracranial aneurysm.
2016-12-01 | GSE75436 | GEO