Inflammation and iron metabolism in adult patients with epilepsy: Does a link exist?

Tombini, Mario; Squitti, Rosanna; Cacciapaglia, Fabio; Ventriglia, Mariacarla; Assenza, Giovanni; Benvenga, Antonella; Pellegrino, Giovanni; Campana, Carmen; Assenza, Federica; Siotto, Mariacristina; Pacifici, L; Afeltra, Antonella; Rossini, Paolo Maria

doi:10.1016/j.eplepsyres.2013.09.010

Cited by 35 publications

(30 citation statements)

References 59 publications

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“…Andro et al (2013) conducted a systematic review of the literature from the past 30 years to investigate the relationship between anemia and cognitive performance in the elderly, including dementia in a community dwelling population. They reported a significant association between anemia and cognitive functions and between anemia and global cognitive deterioration with low Hb An Italian group (Tombini et al, 2013) investigated the link between inflammation and iron metabolism in epileptic patients (n=37, aged 51.3±18.8, 68% women; period between seizures). Epilepsy affects approximately 50 million people worldwide.…”

Section: Key Pointsmentioning

confidence: 99%

Iron status in the elderly: A review of recent evidence

Wawer

Jennings

Fairweather‐Tait

2018

Mechanisms of Ageing and Development

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A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases). Each section of this review concludes with key points from the relevant papers. The overall findings were that disturbed iron metabolism plays a major role in a large number of conditions associated with old age. Correction of iron deficiency/overload may improve disease prognosis, but diagnosis of iron deficiency requires appropriate cut-offs for biomarkers of iron status in elderly men and women to be agreed. Iron deficiency (with or without anemia), anemia of inflammation, and anemia of chronic disease are all widespread in the elderly and, once identified, should be investigated further as they are often indicative of underlying disease. Management options should be reviewed and updated, and novel therapies, which show potential for treating anemia of inflammation or chronic disease, should be considered.

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Section: Key Pointsmentioning

confidence: 99%

Iron status in the elderly: A review of recent evidence

Wawer

Jennings

Fairweather‐Tait

2018

Mechanisms of Ageing and Development

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“…Epilepsy is a common clinical neurological disease, with a prevalence of approximately 1%, that is highly associated with inflammation and oxidative stress [1–4]. Epilepsy is characterized by uncontrolled discharges caused by neuronal hyperactivity in the temporal lobe and the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Auricular Electroacupuncture Reduced Inflammation-Related Epilepsy Accompanied by Altered TRPA1, pPKCα, pPKCε, and pERk1/2 Signaling Pathways in Kainic Acid-Treated Rats

Lin

Hsieh

2014

Mediators of Inflammation

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Background. Inflammation is often considered to play a crucial role in epilepsy by affecting iron status and metabolism. In this study, we investigated the curative effect of auricular acupuncture and somatic acupuncture on kainic acid- (KA-) induced epilepsy in rats. Methods. We established an epileptic seizure model in rats by KA (12 mg, ip). The 2 Hz electroacupuncture (EA) was applied at auricular and applied at Zusanli and Shangjuxu (ST36-ST37) acupoints for 20 min for 3 days/week for 6 weeks beginning on the day following the KA injection. Results. The electrophysiological results indicated that neuron overexcitation occurred in the KA-treated rats. This phenomenon could be reversed among either the auricular EA or ST36-ST37 EA treatment, but not in the sham-control rats. The Western blot results revealed that TRPA1, but not TRPV4, was upregulated by injecting KA and could be attenuated by administering auricular or ST36-ST37 EA, but not in the sham group. In addition, potentiation of TRPA1 was accompanied by increased PKCα and reduced PKCε. Furthermore, pERK1/2, which is indicated in inflammation, was also increased by KA. Furthermore, the aforementioned mechanisms could be reversed by administering auricular EA and could be partially reversed by ST36-ST37 EA. Conclusions. These results indicate a novel mechanism for treating inflammation-associated epilepsy and can be translated into clinical therapy.

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“…There are no clear data regarding the association between the decrease of blood serum iron and brain inflammation. Only one study in the past evidenced an increase of serum level of soluble transferrin receptor in nonanemic patients with multiple sclerosis with active disease reflecting an increased iron turnover . The possible interaction between inflammation and iron metabolism has already been investigated in epilepsy by studying iron‐deficiency anemia in febrile seizures, but the results were somewhat conflicting …”

Section: Links Between Proinflammatory Cytokines and Iron Metabolism mentioning

confidence: 99%

“…Only one study in the past evidenced an increase of serum level of soluble transferrin receptor in nonanemic patients with multiple sclerosis with active disease reflecting an increased iron turnover. 23 The possible interaction between inflammation and iron metabolism has already been investigated in epilepsy by studying iron-deficiency anemia in febrile seizures, but the results were somewhat conflicting. 22 A recent study evaluated the serum levels of cytokines and the markers of iron metabolism, including the hemoglobin concentration (Hgb), the hematocrit (Hct), the transferrin level (Tf) and the ratio of ceruloplasmin to transferrin (Cp/Tf), in 37 adults with focal epilepsy during the interictal period.…”

Section: Links Between Proinflammatory Cytokines and Iron Metabolism mentioning

confidence: 99%

Prospective clinical trials to investigate clinical and molecular biomarkers

et al. 2017

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Among clinical studies, randomized studies as well as well-designed observational studies are providing the highest quality data. In addition, these studies represent a good opportunity to examine biomarkers of ictogenesis and epileptogenesis. To date, no validated molecular or cellular biomarker exists for any aspect of epilepsy. We provide an overview of the inflammatory biomarkers under investigation in prospective clinical studies in epilepsy: proinflammatory cytokines in prolonged febrile seizure; High Mobility Group Box 1 (HMGB1) as a prognosis biomarker in epilepsy and the interaction between inflammation and metabolism, in particular, iron metabolism, in epilepsy. The designs of the European Union EPISTOP project following prospectively patients with tuberous sclerosis from birth to the start of the epilepsy and of the Standard and New Antiepileptic Drugs-II study illustrate how such studies can be used to find new inflammatory biomarkers of ictogenesis and epileptogenesis. If we want to bridge the current gap between having numerous biomarker candidates from preclinical studies and their selective use in clinical practice, we need to explore multiple biologic systems, not just including inflammation. In addition, it is crucial that those involved in the design and support of relevant clinical studies recognize this gap and act accordingly, and in the interests of improving the diagnosis and prognosis for epilepsy.

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Inflammation and iron metabolism in adult patients with epilepsy: Does a link exist?

Cited by 35 publications

References 59 publications

Iron status in the elderly: A review of recent evidence

Iron status in the elderly: A review of recent evidence

Auricular Electroacupuncture Reduced Inflammation-Related Epilepsy Accompanied by Altered TRPA1, pPKCα, pPKCε, and pERk1/2 Signaling Pathways in Kainic Acid-Treated Rats

Prospective clinical trials to investigate clinical and molecular biomarkers

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