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    • Brain - Intramyelinic Edema

    Image of intramyelinic edema in the brain from a rat
    Normal appearance of myelin in cerebellar white matter stained with Luxol fast blue and cresyl violet in a control rat.
    Figure 1 of 4
    Image of intramyelinic edema in the brain from a rat
    Normal appearance of myelin in cerebellar white matter stained with Luxol fast blue and cresyl violet in a control rat (higher magnification of Figure 1).
    Figure 2 of 4
    Image of intramyelinic edema in the brain from a rat
    Brain, cerebellum-morphologic features of toxin-induced intramyelinic edema in white matter (arrow) stained with Luxol fast blue and cresyl violet in a rat.
    Figure 3 of 4
    Image of intramyelinic edema in the brain from a rat
    Brain, cerebellum-morphologic features of toxin-induced intramyelinic edema in white matter (arrow) stained with Luxol fast blue and cresyl violet in a rat (higher magnification of Figure 3).
    Figure 4 of 4
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    comment:

    The presence of “sponginess” ( Figure 4image opens in a pop-up window , arrow) of the white matter is always of concern to the neuropathologist since it is commonly an artifact of poor fixation and autolysis. Figure 1image opens in a pop-up window and Figure 2image opens in a pop-up window show the normal appearance of myelin in rat cerebellar white matter stained with Luxol fast blue and cresyl violet. Assessment of the tissue for indicators of poor fixation and autolysis is extremely important to determine genuine white matter lesions. Valid white matter lesions such as demyelination have some useful hallmarks of authenticity (see Spinal Cord – Demyelination), such as bilateral symmetry and the presence of swollen axons or macrophages in affected areas. Other white matter lesions such as intramyelinic edema are observed as severe spongiform change of white matter without any evidence of myelin breakdown or cellular reaction. Classically, intramyelinic edema is caused by lipophilic compounds that result in separation of myelin lamellae at the intraperiod line (confirmed by electron microscopy). In the CNS, this is due to the accumulation of fluid in the cytoplasm of oligodendroglial cells. Well-studied examples of this form of white matter lesion include exposure to hexachlorophene, as shown in Figure 3image opens in a pop-up window and Figure 4image opens in a pop-up window . Chronic exposure to hexachlorophene also produces astrocytic hypertrophy and proliferation, as demonstrated by glial fibrillary acid protein immunohistochemical staining. Removal of hexachlorophene exposure has been shown to lead to a reversal of the clinical and microscopic spongiform effects in rats.

    recommendation:

    In NTP studies where intramyelinic edema cannot be differentiated from demyelination or axonopathy under light microscopy, the lesion should be diagnosed as white matter vacuolation. This should be followed by special evaluation by a neuropathologist. In the case of suspected intramyelinic edema, where axonopathy and inflammatory responses are generally absent, examination of only well-fixed material by electron microscopy may be confirmatory. When present in NTP studies, the subsite should be noted and lesion severity graded.

    references:

    Kennedy GL Jr, Dressler IA, Richter WR, Keplinger ML, Calandra JC. 1976. Effects of hexachlorophene in the rat and their reversibility. Toxicol Appl Pharmacol 35:137-145.
    Abstract: http://www.sciencedirect.com/science/article/pii/0041008X76901198

    Purves DC, Garrod IJ, Dayan AD. 1991. A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat. Hum Exp Toxicol 10:439-444.
    Abstract: http://www.ncbi.nlm.nih.gov/pubmed/1687857

    Tripier MF, Berard M, Toga M, Martin-Bouyer G, Le Breton R, Garat J. 1981. Experimental hexachlorophene encephalopathy in mice and baboons: Light and electron microscopic study. Acta Neuropathol Suppl 7:40-43.
    Abstract: http://www.ncbi.nlm.nih.gov/pubmed/6939279

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    Web page last updated on: June 13, 2014