A novel approach to quantify different iron forms in ex-vivo human brain tissue

Abstract

We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40–50 nm, which is not compatible with the ferritin protein, the core of which is typically 6–8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

(–)-Epicatechin Reduces the Blood Pressure of Young Borderline Hypertensive Rats During the Post-Treatment Period

“…However, the size of the iron particles and/or their chemical moiety seems to be unchanged, as coercivity and remanent magnetisation remained unaltered. SQUID magnetometry is a novel approach to quantify different iron forms in biological samples with high sensitivity that might provide new information for the understanding of the pathomechanisms of various diseased states as described previously [40,43]. The relative reduction of iron-containing compounds in Epi-treated vs. control rats in this study might be related to the inhibition of iron absorption in the enterocytes by Epi or its metabolites [56].…”

“…A Quantum Design MPMS-XL 7AC (SQUID) magnetometer with a reciprocating sample operation option (with differential sensitivity of 10 −11 Am 2 up to 0.25 T and 10 −10 Am 2 up to 7 T) was used to compare the relative content of iron and iron-containing compounds in the blood samples. The advantage of this method is its ability to determine all of the iron forms in a small sample of biological material, with high sensitivity [40][41][42].…”

“…Thus, we obtained a dry sample of the blood in a homogeneous ambient without the need for a gelatine capsule, which is usually the source of an additional magnetic signal. The magnetic characteristics of the samples were measured in the form of isothermal hysteresis curves [40] at a temperature of 2 K (−271.15 • C) and at a magnetic field up to 7 T when the saturation magnetisation (M s ) was reached. M s is the parameter for determining the concentration of magnetic particles in the biological samples, of which iron is a dominant component under the conditions used in this study.…”

Effects of Alzheimer’s disease and formalin fixation on the different mineralised-iron forms in the human brain

“…Moreover, magnetometry requires minimal sample preparation, contrary to TEM, thus lowering the risk of sample contamination. The observation that IRM curves obtained from human material saturate at magnetic fields of 300 mT or lower, and at temperatures between 50 K and 293 K 2,3,13,17,19,20 , and the occasional observation of the Verwey transition 3,19 , support the use of magnetometry techniques to detect and potentially quantify magnetite and/or oxidised magnetite, i.e. maghemite, nanoparticles in post-mortem or ex-vivo human samples.…”

H-Field Contribution to the Electromagnetic Energy Deposition in Tissues Similar to the Brain but Containing Ferrimagnetic Particles, During Use of Face-Held Radio Transceivers

“…The concentrations are in the range 0.2-12 µg of magnetic material per gram of dry tissue, and the diameters are spread between 10-150 nm. Moreover, in December 2016, the authors of [6] have shown that a combination of two specific methods offers a unique possibility to study and properly characterize the iron accumulation in the human brain. They also formulated the observation that magnetic moments of magnetite/maghemite nanoparticles are blocked for sizes exceeding 40-50 nm at the room temperature.…”