Necrosis and myelomalaic lesions in acute experimental allergic encephalomyelitis in guinea pigs

Mohamed Noorulla, G. C. Sensharma


Background: Multiple Sclerosis (MS) and its animal model Experimental Allergic Encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system, in which the myelin sheath has been considered to be the primary target for many years. However, an increasing number of reports have focused on neurodegenerative aspects of the disease pathogenesis. Damage to axons is taken as a key factor of disability in multiple sclerosis, but its pathogenesis is largely unknown. Axonal injury is believed to occur as a consequence of demyelination and was recently shown to be a feature even of the early disease stages. It is evident that the crucial distinction between primary and secondary demyelination depends on the preservation or the destruction of the axons and the neuronal elements.

Methods:EAE was induced in the adult healthy guinea pigs by weekly intradermal injections of homologous whole brain and spinal cord antigen together with complete Freund’s adjuvant into the foot pad of the animal. The animals were observed for clinical features of the disease after injection.

Results:The histological observation revealed two stages of EAE; an initial inflammatory stage followed by demyelination. The inflammatory lesions were focal and invariably related to blood vessels. The inflammatory lesions consisted of perivascular cuffings with lymphocytes and mononuclear cells in the perivascular space and surrounding parenchyma. Perivascular demyelination was restricted to that part of the white matter which was infiltrated by mononuclear cells. The fibres in demyelinating lesions were demyelinated. Perivascular demyelination is followed by patchy demyelination and large plaques of demyelination. Neuronal and axonal damage, necrosis, tissue degeneration and cavity formation were seen in those animals which died during the acute phase of the disease. These changes were found in the spinal cord, brainstem and cerebellum.  

Conclusion:The changes observed in results lead to the conclusion that the acute EAE with severity of disease is no more a primary demyelinating disease.   



EAE, MS, Inflammation, Demyelination, Necrosis, Neurodegeneration

Full Text:



Levine S. Relationship of experimental allergic encephalomyelitis to human disease. Res Pub Assoc Res Nerv Ment Dis. 1971;49:33-49.

Paterson PY. EAE: role of fibrin deposition in immunopathogenesis of inflammation in rats. Fed Proc. 1976;35(13):2428-34.

Levine, Sowinski. Necrotic myelopathy (myelomalacia) in rats with allergic encephalomyelitis treated with tilorone. Am J Pathol. 1976;82:381-92.

Keith AB, McDermott JR. Optimum conditions for inducing relapsing experimental allergic encephalomyelitis in guinea pigs. J Neurol Sci. 1980;46:353-64.

Kerlero de Rosbo N, Bernard CCA, Simmons RD, Carnegie PR. Concomitant detection of changes in myelin basic protein and permeability of blood-spinal cord barrier in acute experimental autoimmune encephalomyelitis by electroimmunoblotting. J Neuroimmunol. 1985;9:349-61.

Brosnan CF, Goldmuntz EA, Cammer W, Factor SM, Bloom BR, Norton WT. Prazosin, an alpha-1 adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat. Proc Natl Acad Sci USA. 1985;82:5915-9.

Floris S, Blezer EL, Schreibelt G, Döpp E, van der Pol SM, Schadee-Eestermans IL, et al. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain. 2004;127(3):616-27.

Polfliet MM, van de Veerdonk F, Dopp EA, van Kesteren‐Hendrikx EM, van Rooijen N, Dijkstra CD, et al. The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis. J Neuroimmunol. 2002;122:1-8.

Bauer J, Berkenbosch F, Van Dam AM, Dijkstra CD. Demonstration of interleukin‐1 beta in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level. J Neuroimmunol. 1993;48:13-21.

Mato M, Ookawara S, Sakamoto A, Aikawa E, Ogawa T, Mitsuhashi U, et al. Involvement of specific macrophage‐lineage cells surrounding arterioles in barrier and scavenger function in brain cortex. Proc Natl Acad Sci USA. 1996;93:3269-74.

Prat A, Biernacki K, Wosik K, Antel JP. Glial cell influence on the human blood‐brain barrier. Glia. 2001;36:145-55.

Juhler M, Barry DI, Offner H, Konat G, Klinken L, Paulson OB. Blood-brain and blood-spinal cord barrier permeability during the course of experimental allergic encephalomyelitis in the rat. Brain Res. 1984 Jun;302(2):347-55.

Levine S. Hyperacute, neutrophilic, and localized forms of experimental allergic encephalomyelitis: a review. Acta Neuropathol. 1974;28(3):179-89.

Levine S, Wenk EJ. A hyperacute form of allergic encephalomyelitis. Am J Pathol. 1965;47:61-88.

Levine S. Relationship of experimental allergic encephalomyelitis to human disease. Res Pub Assoc Res Nerv Ment Dis. 1971;49:33-49.

Skundric DS. Experimental models of relapsing-remitting multiple sclerosis: current concepts and perspective. Curr Neurovasc Res. 2005 Oct;2(4):349-62.

Seymour Levine MD, Richard Sowinski MS. Localization of toxic encephalopathies near lesions of experimental allergic encephalomyelitis. Am J Pathol. 1982;107:135-41.

Herz J, Zipp F, Siffrin V. Neurodegeneration in autoimmune CNS inflammation. Exp Neurol. 2010 Sep;225(1):9-17.

Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurol. 2002 Oct;59(8):1224-31.

Stone MJ, Hawkins CP. A medical overview of encephalitis. Neuropsychol Rehabil. 2007;17(4-5):429-49.

Archer H, Wall R. Acute haemorrhagic leukoencephalopathy: two case reports and review of the literature. J Infect. 2003 Feb;46(2):133-7.

Davies NW, Sharief MK, Howard RS. Infection-associated encephalopathies: their investigation, diagnosis, and treatment. J Neurol. 2006 Jul;253(7):833-45.

Tenembaum S, Chitnis T, Ness J, Hahn JS. Acute disseminated encephalomyelitis. Neurol. 2007 Apr;68(16 Suppl 2):S23-36.

Bjartmar CL, Wujek JR, Trapp BD. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci. 2003 Feb;206(2):165-71.

Brück W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol. 2005 Nov;252(Suppl 5):v3-9.

Field EJ, Raine CS. Experimental allergic encephalomyelitis in the rhesus monkey. An electron microscopic study. J Neurol Sci. 1969 May-Jun;8(3):397-411.

Bjartmar C, Wujek JR, Trapp BD. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci. 2003 Feb;206(2):165-71.

Charcot M. Histologie de la sclérose en plaques. Gaz Hop (Paris). 1868;41:554-5, 557-8, 566.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338:278–85.

Bitsch, Schuchardt, Bunkowski, Kuhlmann, Brück. Acute axonal injury in multiple sclerosis: correlation with demyelination and inflammation. Brain. 2000;123(6):1174-83.

Levine. Presidential address: allergic encephalomvelitis: cellular transformation and vascular blockade. J Neuropathol Exp Neurol. 1970;29:6-20.

Seymour Levine, Eugene J. Wenk. A hyperacute form of allergic encephalomyelitis. Amer J Pathol. 1965;47(1):61-88.