Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis.
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.
Forge
J K
JK
Department of Molecular and Integrative Physiology and the Smith Mental Retardation and Human Development Center, University of Kansas Medical Center, Kansas City 66160, USA.
Pedchenko
T V
TV
LeVine
S M
SM
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009836:Oligodendroglia / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D007501:Iron