Brain - Axonopathy







comment:
“Axonopathy” is a generic term describing a variety of lesions of the axon occurring in brain, spinal cord, and peripheral nerve. Care must be taken at low magnifications to ensure that the criteria for axonopathy (axonal swelling, fragmentation, loss, etc.) are not disregarded as artifactual vacuolation. Its presence in defined regions of brain and spinal cord and frequent symmetrical distribution are useful clues to its genuine nature. Close examination of all regions of white matter and nerve tissue is required to correctly discover and interpret this type of lesion. Age-related axonopathy occurs commonly in the cauda equina, ventral spinal nerve roots, ventral and lateral spinal funiculi, sciatic and brachial nerves, and lower brainstem. Caution should be given to interpretation of spinal and radicular (nerve root) axonopathy in aged rats since it may be a result of senescence and has an incidence of 75-90% in rats 24 or more months of age. In specialized toxicologic-neuropathologic studies, use of special axonal stains such as Bielschowsky silver impregnation and de Olmos amino cupric silver to highlight the normal axon and axonal lesions, respectively, may be helpful in delineating the severity and distribution of these often subtle lesions.Figure 1


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recommendation:
In NTP studies, the term “axonopathy” is preferred for all forms of axonal injury. This lesion should be diagnosed in control and treated animals with its anatomic subsite location. Severity grade should be included with criteria, allowing a decision on its treatment-related significance to be based on incidence and severity. Searching diligently for tangible criteria of axonopathy is important in confirming the genuine nature of the lesions at several stages of their evolution. In NTP studies where focal vacuolar lesions in white matter are of uncertain pathogenesis to the study pathologist, or in studies where the lesion cannot be differentiated from demyelination or intramyelinic edema, the lesion should be diagnosed as white matter vacuolation. The narrative should describe features including whether the lesion is focal, unilateral, or bilateral. This should be followed by special evaluation by a neuropathologist.references:
Baker HJ, Lindsey JR, Weisbroth SH, eds. 1979. The Laboratory Rat, Vol 1: Biology and Diseases. Academic Press, New York.
Beirowski B, Adalbert R, Wagner D, Grumme DS, Addicks K, Ribchester RR, Coleman MP. 2006. The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves. BMC Neurosci 6:6. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/15686598
Lubinska L. 1977. Early course of Wallerian degeneration in myelinated fibres of the rat phrenic nerve. Brain Res 130:47-63. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/884520
Stoll G, Griffin JW, Li CY, Trapp BD. 1989. Wallerian degeneration in the peripheral nervous system: Participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol 18:671-683. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/2614485
Tabas I. 1997. Free cholesterol-induced cytotoxicity. A possible contributing factor to macrophage foam cell necrosis in advanced atherosclerotic lesions. Trends Cardiovasc Med 7:256-263. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/21235894
Tenkova TI, Goldberg MP. 2007. A modified silver technique (de Olmos stain) for assessment of neuronal and axonal degeneration. Methods Mol Biol 399:31-39. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/18309923
Waller A. 1850. Experiments on the section of glossopharyngeal and hypoglossal nerves of the frog and observations of the alternatives produced thereby in the structure of their primitive fibers. Philos Trans R Soc Lond Biol 140:423-429.
Web page last updated on: January 07, 2014