Axonal Pathology and Loss Precede Demyelination and Accompany Chronic Lesions in a Spontaneously Occurring Animal Model of Multiple Sclerosis

作者：Seehusen Frauke; Baumgaertner Wolfgang

来源：Brain Pathology, 2010, 20(3): 551-559.

DOI：10.1111/j.1750-3639.2009.00332.x

• axonal pathology
• beta-APP
• canine distemper virus

Axonal damage has been highlighted recently as a cause of neurological disability in various demyelinating diseases, including multiple sclerosis, either as a primary pathological change or secondary due to myelin loss. To characterize and quantify axonal damage and loss in canine distemper demyelinating leukoencephalomyelitis (DL), formalin-fixed paraffin-embedded cerebella were investigated histochemically and immunohistochemically using the modified Bielschowsky's silver stain as well as antibodies against nonphosphorylated (n-NF), phosphorylated neurofilament (p-NF) and beta-amyloid precursor protein (beta-APP). Injured axons characterized by immunoreactivity against n-NF and beta-APP were detected in early distemper lesions without demyelination. In subacute and chronic demyelinating lesions the number of injured axons increased. Moreover, a significant decrease in axonal density was observed within lesions and in the normal appearing white matter in DL as determined by morphometric analyses using Bielschowsky's silver stain and p-NF immunohistochemistry. Summarized, the observed findings indicate that axonal damage (i) occurs early in DL; (ii) can be detected before myelin loss; and (iii) represents a pivotal feature in advanced lesions. It must be postulated that axonal damage plays an important role in the initial phase as a primary event and during progression of nervous distemper as a result of demyelination.

• 出版日期2010-5