Multimodal microscopic and spectroscopic characterisation of heterogeneous iron oxyhydroxides in the human globus pallidus

Abstract

Iron is essential for neuronal metabolism, neurotransmitter synthesis, and enzymatic function; however, dysregulated accumulation contributes to oxidative stress and neurodegeneration. The basal ganglia, particularly the globus pallidus, represent a hotspot for iron deposition, yet the precise structural forms and their implications remain incompletely understood. Here, a multimodal approach was applied combining Raman microspectroscopy, light microscopy, transmission (TEM) and scanning electron microscopy coupled with energy-dispersive X-ray analysis (SEM–EDX) to characterise iron-rich deposits in post-mortem human globus pallidus. Tissue samples from six individuals without neurological disease were examined. Perls’ staining revealed iron-positive, spherical inclusions 10–20 µm in diameter. Raman spectroscopy revealed bands at 268–278, 490, 526, and 603 cm⁻¹, as well as broader signals at 1259–1349 cm⁻¹, consistent with magnetite, maghemite, hematite, and ferritin-like structures. Additional vibrations in the 682–1532 cm⁻¹ range indicated interactions with organic matrices, such as protein or lipid components. SEM–EDX identified both regular and irregular iron-rich particles with multielemental composition, including C, O, Al, Si, P, S, Ca, Cr, and Ni, in addition to Fe. TEM examination showed the micrometre-sized particles of hematite and aggregation of ferrihydrite. These findings suggest that iron deposits in the globus pallidus comprise heterogeneous mixtures of oxides and hydroxides with variable crystallinity. Depending on their crystallinity and surface reactivity, such phases may represent a potential pool of redox-active iron; however, the present study did not assess markers of oxidative stress, and their physiological versus pathological significance remains to be established.