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Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis
J K Forge1, T V Pedchenko, S M LeVine
1Department of Molecular and Integrative Physiology and the Smith Mental Retardation and Human Development Center, University of Kansas Medical Center, Kansas City 66160, USA.
Abstract:
Iron has been proposed to promote oxidative tissue damage in multiple sclerosis (MS). In order to gain insights about how iron gets processed during MS, the deposition of iron was investigated in the CNS of mice with experimental allergic encephalomyelitis (EAE), which is a commonly used animal model of MS. Control mice (adjuvant only) and EAE mice (myelin basic protein plus adjuvant), were sacrificed at 4-8 days (preclinical phase), 10-13 days (clinical phase), or 18 days (recovery phase) post injection. Sections from the cerebrum, hindbrain, and cervical, thoracic and lumbar spinal cord were stained as previously described (J. Neurosci. Res. 29:413, 1991), and scored blindly for histopathological staining. There was minimal histopathological staining at any age in control animals or during the preclinical stage in EAE animals. At the clinical stage of EAE, stained pathological features (macrophages, extravasated RBC and granular staining) were significantly increased compared to the preclinical stage. In the recovery phase, macrophage and granular staining persisted but there was loss of extravasated RBC. Dual labeling studies revealed that granular deposits were present in astrocytes and in locations that appeared to be extracellular. In order to gain insights about the origin of iron deposits in EAE mice, additional studies were performed on brains of mice with extravasated blood lesions. These brains had granular, macrophage and RBC staining. Thus, each of the stained features in EAE animals could be due to the extravasation of blood which occurs in the SJL model of EAE, although some of the iron could have originated from myelin and oligodendrocytes damaged during EAE.
Insights
Iron accumulation in the central nervous system (CNS) during multiple sclerosis (MS) was studied in mice with experimental allergic encephalomyelitis (EAE). Iron deposits were linked to blood extravasation and damaged myelin, suggesting potential origins of iron in MS.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Iron is implicated in oxidative tissue damage in multiple sclerosis (MS).
- Understanding iron processing in MS is crucial for therapeutic insights.
- Experimental allergic encephalomyelitis (EAE) serves as a relevant animal model for MS.
Purpose of the Study:
- To investigate iron deposition patterns in the CNS of EAE mice.
- To correlate iron processing with disease progression in MS models.
- To identify the cellular and extracellular origins of iron deposits in EAE.
Main Methods:
- Histopathological staining of CNS tissue from control and EAE mice at different disease stages (preclinical, clinical, recovery).
- Blind scoring of stained pathological features including macrophages, extravasated red blood cells (RBC), and granular deposits.
- Dual labeling studies to identify the location of granular deposits (intracellular/extracellular).
- Analysis of brains with extravasated blood lesions to determine iron source.
Main Results:
- Minimal histopathological staining in control mice and during the preclinical EAE stage.
- Significant increase in macrophages, extravasated RBC, and granular staining at the clinical EAE stage.
- Persistence of macrophage and granular staining, with loss of extravasated RBC during recovery.
- Granular iron deposits found in astrocytes and extracellularly.
- Stained features in EAE mice consistent with blood extravasation.
Conclusions:
- Iron deposition in the CNS of EAE mice is associated with disease progression.
- Extravasated blood is a primary source of iron deposits in this MS model.
- Myelin and oligodendrocyte damage may also contribute to iron accumulation in EAE.
- Findings provide insights into iron metabolism during demyelinating diseases like MS.