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Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Regional brain iron deposition and functional alterations in thalassemia: a multimodal human study with murine
Jingxuan Shao1,2, Cheng Tang3, Yanfei Lu1,4
1Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background And Objectives:
Chronic anemia and systemic iron overload in thalassemia major (TM) patients may result in neurological deficits, although researchers have not completely elucidated their specific impacts on the brain. This study employed a multimodal research methodology to investigate the characteristics and intrinsic connections of cerebral iron deposition, cerebral dysfunction, and cognitive impairment in TM patients, providing theoretical support for brain monitoring and neuroprotective interventions in this condition.
Methods:
We prospectively enrolled 88 patients with TM, including 46 transfusion-dependent thalassemia (TDT) and 42 non-transfusion-dependent thalassemia (NTDT) patients, alongside 79 healthy controls (HCs), between September 2022 and September 2025. All participants underwent quantitative susceptibility mapping (QSM), resting-state functional MRI (rs-fMRI), and assessments using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Serum biomarkers including S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) were quantified. A parallel murine model of iron overload was created for validation purposes.
Results:
QSM revealed localised iron deposition in the red nucleus, substantia nigra, subthalamic nucleus, and globus pallidus of patients with TM (F = 3.294-13.305, P = 0.001-0.040). The susceptibility values in these basal ganglia regions demonstrated a negative link with cognitive scores (r = - 0.27 to - 0.43, P < 0.05), suggesting that localised iron buildup correlates with cognitive decline.Rs-fMRI revealed significant irregularities in spontaneous brain activity across the frontal lobe-limbic system-cerebellar network, which correlated with deficits in attention, memory, and language functions as assessed by the cognitive evaluation scale. A murine iron overload model further demonstrated that cerebral iron deposition originates in the choroid plexus.Serum S100B and NSE concentrations increased progressively from HCs to NTDT and TDT groups (P < 0.05), reflecting gradual loss of astrocytic and neuronal integrity driven by worsening systemic iron overload.
Conclusions:
TM patients, especially those with TDT, exhibit measurable cognitive impairment and cerebral functional remodeling, which are tightly associated with regional brain iron deposition. This study's findings establish a theoretical foundation for the early detection of thalassemia-associated neurological problems and the formulation of focused therapeutic strategies.
