Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

Abstract

Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

“…As recently reviewed in this journal, 163 many GM areas (including the thalamus, dentate nucleus, basal ganglia, and rolandic cortex) commonly show hypointensity on T2-weighted images in patients with MS. Iron deposition has been postulated to be a cause of this hypointensity, as it reduces T2-relaxation times and is found pathologically to be in excess in the MS brain. 164 Furthermore, biochemical abnormalities related to iron are seen in patients with MS. 163 It remains unclear whether iron deposition contributes to secondary damage or is purely an epiphenomenon.…”

“…164 Furthermore, biochemical abnormalities related to iron are seen in patients with MS. 163 It remains unclear whether iron deposition contributes to secondary damage or is purely an epiphenomenon. T2 hypointensity in GM has been related to brain atrophy, physical disability, and cognitive impairment in patients with MS. 136,[165][166][167][168] Prior studies determining T2 hypointensity have relied on normalized intensity measurements rather than relaxometric studies.…”

Different Iron-Deposition Patterns of Multiple System Atrophy with Predominant Parkinsonism and Idiopathetic Parkinson Diseases Demonstrated by Phase-Corrected Susceptibility-Weighted Imaging

“…ron plays an important role in brain function 1 ; however, brain iron deposition has been proposed to play an important role in the pathophysiology of neurodegenerative disease. It has been demonstrated that abnormal iron accumulation occurs in the brains of patients with various neurodegenerative diseases such as IPD, multiple system atrophy, Alzheimer disease, and MS. [2][3][4][5] Parkinsonism is a clinical syndrome characterized by tremors, muscle rigidity, and bradykinesia.…”

Anomalous Venous Blood Flow and Iron Deposition in Multiple Sclerosis

“…The role of metallobiology in neurodegenerative disorders has long been implicated, with particular attention given to iron as it is one of the most important redox metals, which have been largely linked to senile toxicity and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases and aging patients (Bush, 2000;Sullivan, 2004;Altamura and Muckenthaler, 2009;Stankiewicz et al, 2007;Stankiewicz and Brass, 2009). The redox switching capability of iron from ferrous to ferric state, and vice versa, makes it one of the most dangerous catalytic elements responsible for the neurodegenerative process (Levenson and Tassabehji, 2004).…”