Please wait a minute...
Journal of Integrative Agriculture  2013, Vol. 12 Issue (2): 334-343    DOI: 10.1016/S2095-3119(13)60233-6
ANIMAL SCIENCE · VETERINARY SCIENCE Advanced Online Publication | Current Issue | Archive | Adv Search |
Pathogenesis of Demyelinating Encephalopathy in Dogs with Spontaneous Acute Canine Distemper
 PAN Yao-qian, LIU Xing-you, MENG Li-ping, ZHU Guang-rui, XIA Yin-ke, CHEN Jin-shan , Yoshikawa Takashi
1.Department of Veterinary Pathology, College of Animal Sciences, Henan Institute of Science and Technology, Xinxiang 453003, P.R.China
2.Department of Microbiology and Immunology, Northwestern University, Feinberg Medical School, 303 E. Chicago Ave, Chicago IL 60611, USA
3.Department of Veterinary Pathology, School of Veterinary Medicine and Animal Science, Kitasato University, Towada, Aomori 034-8628,Japan
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
摘要  So far, the pathogenesis of demyelination caused by canine distemper virus (CDV) in the central nervous system has remained unclear, although a lot of studies have been done extensively. To further investigate the relation of variety cells in brain to demyelination, this study was performed on 15 dogs with spontaneous acute canine distemper and 2 controls. According to anatomical relation, the brain was divided into cerebrum, cerebral stem and cerebellum. The sections with no, mild, moderate, or severe demyelinating lesions were selected respectively and stained by HE and immunohistochemistry. Immuno-localisation of CDV antigen was used to confirm CDV infection. The brain was examined for co-localisation of the CDV antigen with either an astrocyte-specific marker, glial fibrillary acidic protein (GFAP), or an oligodendrocyte-specific marker, galactocerebroside (GalC). Apoptotic cell was detected by TdT-mediated nick end-labeling assay (TUNEL). The results demonstrated that the local disturbance of blood circulation mainly included congestion, edema, thrombosis, and disseminated intravascular coagulation (DIC). The CDV neucleocapsid protein positive reaction, metabolic disorder and apoptosis of oligodendrocytes were observed in demyelinating areas. Lots of astrocytes displayed CDV antigen-positive, especially in their process. Some of them became apoptotic cell confirmed by TUNEL staining. Fibrous astrocytes showed more intense GFAP-positive in mild and moderate demyelinating area. Some of nervous cells located in pyramidal cell layers and nucleus nervi were in degeneration, necrosis. Satellitosis, neuronophagia and apoptotic neurons were examined by hematoxylin and eosin (HE) and TUNEL staining. The results suggested that the demyelinating changes in brain tissues infected with CDV mainly related to the metabolic disorder and apoptosis of ogliodendrocytes and astrocytes; also involved with the local disturbance of blood circulation and some neuron lost.

Abstract  So far, the pathogenesis of demyelination caused by canine distemper virus (CDV) in the central nervous system has remained unclear, although a lot of studies have been done extensively. To further investigate the relation of variety cells in brain to demyelination, this study was performed on 15 dogs with spontaneous acute canine distemper and 2 controls. According to anatomical relation, the brain was divided into cerebrum, cerebral stem and cerebellum. The sections with no, mild, moderate, or severe demyelinating lesions were selected respectively and stained by HE and immunohistochemistry. Immuno-localisation of CDV antigen was used to confirm CDV infection. The brain was examined for co-localisation of the CDV antigen with either an astrocyte-specific marker, glial fibrillary acidic protein (GFAP), or an oligodendrocyte-specific marker, galactocerebroside (GalC). Apoptotic cell was detected by TdT-mediated nick end-labeling assay (TUNEL). The results demonstrated that the local disturbance of blood circulation mainly included congestion, edema, thrombosis, and disseminated intravascular coagulation (DIC). The CDV neucleocapsid protein positive reaction, metabolic disorder and apoptosis of oligodendrocytes were observed in demyelinating areas. Lots of astrocytes displayed CDV antigen-positive, especially in their process. Some of them became apoptotic cell confirmed by TUNEL staining. Fibrous astrocytes showed more intense GFAP-positive in mild and moderate demyelinating area. Some of nervous cells located in pyramidal cell layers and nucleus nervi were in degeneration, necrosis. Satellitosis, neuronophagia and apoptotic neurons were examined by hematoxylin and eosin (HE) and TUNEL staining. The results suggested that the demyelinating changes in brain tissues infected with CDV mainly related to the metabolic disorder and apoptosis of ogliodendrocytes and astrocytes; also involved with the local disturbance of blood circulation and some neuron lost.
Keywords:  acute canine distemper       demyelinating encephalopathy       oligodendrocyte       astrocyte       apoptosis  
Received: 21 July 2011   Accepted:
Fund: 

This work was Supported by the National Natural Science Foundation of China (30771601).

Corresponding Authors:  Correspondence PAN Yao-qian, Mobile: 13223756880, E-mail: panyaoqian@163.com     E-mail:  panyaoqian@163.com

Cite this article: 

PAN Yao-qian, LIU Xing-you, MENG Li-ping, ZHU Guang-rui, XIA Yin-ke, CHEN Jin-shan , Yoshikawa Takashi. 2013. Pathogenesis of Demyelinating Encephalopathy in Dogs with Spontaneous Acute Canine Distemper. Journal of Integrative Agriculture, 12(2): 334-343.

[1] Alleinger S, Fonfara S, Kremmer E, Baumgartner W. 2000.Up-regulation of the hyaluronate receptor CD44 incanine distemper demyelinated plaques. ActaNeuropathologica, 99, 138-146

[2] Amude A M, Alfieri A F, Alfieri A A. 2010. Non-conventionalneuro-pathological manifestations of canine distempervirus infection in dogs. In: Mendez-Vilas A, ed., CurrentResearch, Technology and Education Topics inApplied Microbiology and Microbial Biotechnology.Formatex, Badajoz, Spain. pp. 729-736

[3] Axthelm M K, Krakowka S. 1987. Canine distemper virus:the early blood-brain barrier lesion. ActaNeuropathologica, 75, 27-33

[4] Beineke A, Puff C, Seehusen F, Baumgartner W. 2009.Pathogenesis and immunopathology of systemic andnervous canine distemper. Veterinary Immunology andImmunopathology, 127, 1-18

[5] Blakemore W F, Summers B. 1989. Evidence ofoligodendrocyte infection and degeneration in caninedistemper encephalomyelitis. Acta Neuropathologica,77, 550-553

[6] Chulakasian S, Lee M, Wang C, Chiou S, Lin K, Lin F, HsuT, Wong M, Chang T, Hsu W. 2010. Multiplexamplification refractory mutation system polymerasechain reaction (ARMS-PCR) for diagnosis of naturalinfection with canine distemper virus. Virology Journal,7, 22-26

[7] Dalcanto M C, Rabinowitz S G. 1982. Experimental modelsof virus-induced demyelination of the central nervoussystem. Annual Neurology, 11, 107-109

[8] Graber H U, Muller C J, Vandevelde M, Zurbriggen A. 1995.Restricted infection with canine distemper virus leadsto down-regulation of myelin gene transcription incultured oligodendrocytes. Acta Neuropathologica,90, 312-318

[9] Headley S A, Soares I C, Graca D L. 2001. Glial fibrillaryyyacidic protein (GFAP) immunoreactive astrocytes indogs infected with canine distemper virus. Journal ofComparative Pathology, 125, 90-95

[10] Headley S A, Amude A M, Alfieri A F, Bracarence A, AlfieriA A, Summers B A. 2009. Molecular detection of caninedistemper virus and the immunohistochemicalcharacterization of the neurologic lesions in naturallyoccurring old dog encephalitis. Journal of VeterinaryDiagnostic Investigation, 21, 588-597

[11] Higgins R J, Krakowka S G, Metzler A E, Koestner A. 1982.Primary demyelination in experimental canine distempervirus induced encephalomyelitis in gnotobiotic dogs.Acta Neuropathologica, 58, 1-8

[12] Kabakci N, Yarim M, Karahan S, Guvenc T, Yagci B, Safa GS. 2004. Immunohistochemical investigation ofcerebellum in dogs infected with canine distemper virus.Acta Veterinary Hungarica, 52, 327-337

[13] Koutinas A F, Polizopoulou Z S, Baumgaetner W, LekkasS, Kontos V. 2002. Relation of clinical signs topathological changes in 19 cases of canine distemperencephalomyelitis. Journal of Comparative Pathology,126, 47-56

[14] Montgonery D L. 1994. Astrocytes: form functions androles in diseases. Veterinary Journal of Pathology, 31,145-167

[15] Mutinelli F, Vandevelde M, Griot C, Richard A. 1988.Astrocytic infection in canine distemper virus-induceddemyelination. Acta Neuropathologica, 77, 333-335

[16] Nesseler A, Baumgartmer W, Gaedke K, Zurbriggen A. 1997.Abundant expression of viral nucleoprotein mRNA andrestricted translation of the corresponding viral proteinin inclusion body polioencephalitis of canine distemper.Journal of Comparative Pathology, 116, 291-301

[17] Pan Y, Long T, Zhao D, Higuchi S. 2005. Primarydemyelinating encephalopathy in dogs withspontaneous acute canine distemper. Chinese Journalof Veterinary Science, 25, 230-235

[18] Raine C S. 1976. On the development of CNS lesion innatural canine distemper encephalomyelitis. Journal ofNeuron Science, 49, 177-181

[19] Rockborn G. 1958. Further studies on viremia andneutralizing antibodies in maturally acquired distemperin dogs. Archive Gesamte Virology, 8, 500-510

[20] Schobesberger M, Zurbriggen A, Summerfield A,Vandevelde M, Griot C. 1999. Oligodendroglialdegeneration in distemper: apoptosis or necrosis? ActaNeuropathologica, 97, 279-287

[21] Schobesberger M, Zurbriggen A, Doherr M G, WeissenbockH, Vandevelde M, Lassmann H, Griot C. 2002.Demyelination precedes oligodendrocyte loss in caninedistemper virus-induced encephalitis. ActaNeuropathologica, 103, 11-19

[22] Seehusen F, Baumg鋜tner W. 2010. Axonal pathology andloss precede demyelination and accompany chroniclesions in a spontaneously occurring animal model ofmultiple sclerosis. Brain Pathology, 20, 551-559

[23] Stein V M, Czub M, Schreiner N, Moore P F, VandeveldeM, Zurbriggen A, Tipold A. 2004. Microglial cellactivation in demyelinating canine distemper lesions.Journal of Neuroimmunology, 153, 122-131

[24] Stein V M, Schreiner N M, Moore P F, Vandevelde M,Zurbriggen A, Tipold A. 2008. Immunophenotypicalcharacterization of monocytes in canine distemper virusinfection. Veterinary Microbiology, 131, 237-246

[25] Sultan S, Lan N T, Ueda T, Yanmaguchi R, Maeda K, Kai K.2009. Propagation of Asian isolates of canine distempervirus (CDV) in hamster cell lines. Acta VeterinariaScandinavica, 51, 38-42

[26] Summers B A, Greisen H A, Appel M J G. 1978. Possibleinitiation of viral encephalomyelitis in dogs by migratinglymphocytes infected with distemper virus. Lancet, 22,187-189

[27] Summers B A, Greisen H A, Appel M J G. 1979. Early eventsin canine distemper demyelinating encephalomyelitis.Acta Neuropathologica, 46, 1-10

[28] Summers B A, Appel M J G. 1994. Aspects of caninedistemper virus and measles virus encephalomyelitis.Neuropathology Apply Neurobiology, 20, 525-534

[29] Summers B A, Cummings J F, DeLahunta A. 1995. Caninedistemper encephalomyelitis. In: VeterinaryNeuropathaology. Mosby Yearbook, St, Louis. pp. 102-110

[30] Tipold A, Vandevelde M, Jaggy A. 1992. Neurologicalmanifestations of canine distemper virus infection.Journal of Small Animal Practice, 33, 466-470

[31] Vandevelde M, Fankhauser R, Kristensen F, kristensen B.1981. Immunoglobulins in demyelinating lesions incanine distemper encephalitis - an immunohistologicalstudy. Acta Neuropathologica, 54, 31-41

[32] Vandevelde M, Zurbriggen A. 1995. The neurobiology ofcanine distemper virus infection. VeterinaryMicrobiology, 44, 271-280

[33] Wisniewski H, Raine C S, Kay W J. 1972. Observation onviral demyelinating encephalitis. LaboratoryInvestigation, 26, 589-599

[34] Wyss-Fluehmann G, Zurbriggen A, Vandevelde M, PlattetP. 2010. Canine distemper virus persistence indemyelinating encephalitis by swift intracellular cellto-cell spread in astrocytes in controlled by the viralattachment protein. Acta Neuropathologica, 119, 617-630

[35] Wunschnann A, Kremmer E, Baumgartner W. 2000.Phenotypical characterization of T and B cell areas inlymphoid tissues of dogs with spontaneous distemper.Veterinary Immunology and Immunopathology, 73, 83-98

[36] Zurbriggen A, Schmid I, Graber H U, Vandevellde M. 1998.Oligodendroglial pathology in canine distemper. ActaNeuropathologica, 95, 71-77

[37] Zurbriggen A, Yamawaki M, Vandevelde M. 1993. Restrictedcanine distemper virus infection of oligodendrocytes.Laboratory Investigation, 68, 277-284.
[1] Saif ULLAH, Sheeraz MUSTAFA, Wael ENNAB, Muhammad JAN, Muhammad SHAFIQ, Ngekure M. X. KAVITA, Lü Zeng-peng, MAO Da-gan, SHI Fang-xiong. A protective role of resveratrol against the effects of immobilization stress in corpora lutea of mice in early pregnancy[J]. >Journal of Integrative Agriculture, 2020, 19(7): 1857-1866.
[2] LI Fu-hua, ZHENG Shao-jie, ZHAO Ji-chun, LIAO Xia, WU Su-rui, MING Jian. Phenolic extract of Morchella angusticeps peck inhibited the proliferation of HepG2 cells in vitro by inducing the signal transduction pathway of p38/MAPK[J]. >Journal of Integrative Agriculture, 2020, 19(11): 2829-2838.
[3] WANG Jun, SHI xin-jin, SUN Hai-wei, CHEN Hong-jun. Insights into African swine fever virus immunoevasion strategies[J]. >Journal of Integrative Agriculture, 2020, 19(1): 11-22.
[4] RAN Mao-liang, WENG Bo, CAO Rong, PENG Fu-zhi, LUO Hui, GAO Hu, CHEN Bin. miR-34c inhibits proliferation and enhances apoptosis in immature porcine Sertoli cells by targeting the SMAD7 gene[J]. >Journal of Integrative Agriculture, 2019, 18(2): 449-459.
[5] ZHANG Feng, GAO Peng, GE Xin-na, ZHOU Lei, GUO Xin, YANG Han-chun. Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4[J]. >Journal of Integrative Agriculture, 2017, 16(11): 2573-2585.
[6] PAN Chuan-ying, YU Shuai, ZHANG Peng-fei, WANG Bo, ZHU Zhen-dong, LIU Ying-ying, ZENG Wen-xian . Effect of sucrose on cryopreservation of pig spermatogonial stem cells[J]. >Journal of Integrative Agriculture, 2017, 16(05): 1120-1129.
[7] HU Ting-xi, ZHU Hua-bin, SUN Wei-jun, HAO Hai-sheng, ZHAO Xue-ming, DU Wei-hua, WANG Zong-li. Sperm pretreatment with glutathione improves IVF embryos development through increasing the viability and antioxidative capacity of sex-sorted and unsorted bull semen[J]. >Journal of Integrative Agriculture, 2016, 15(10): 2326-2335.
[8] YU De-bing, YU Min-li, LIN Fei, JIANG Bao-chun, YANG Li-na, WANG Si-yu, ZHAO Ying , WNAG Zheng-chao. Morphological and Hormonal Identification of Porcine Atretic Follicles and Relationship Analysis of Hormone Receptor Levels During Granulosa Cell Apoptosis In vivo[J]. >Journal of Integrative Agriculture, 2014, 13(5): 1058-1064.
[9] SHI Ya-ran, WANG Zhan-he, CAO Yong-chun, LU Yan, TIAN Jin-ling, ZhANG Chao, JIA Zi-ye, CHEN Wu. Relationships Between Icariin and Anti-Apoptotic miRNA-21 in Mouse Blastocyst Development In vitro[J]. >Journal of Integrative Agriculture, 2013, 12(4): 663-669.
[10] SUN Gui-rong, LI Yan, KANG Xiang-tao, TIAN Ya-dong, ZHANG Hu , LI Kui. Effect of Beak Trimming Stress on the Apoptosis and Its Related Protein Expression of Chicken Spleen[J]. >Journal of Integrative Agriculture, 2012, 12(4): 639-645.
[11] YOU Hua, ZHU Jin-feng, SHE Rui-ping, CHANG Ling-ling, SHI Rui-han, DING Ye, CHI Li-juan, LIUBin , YUE Zhuo, TIAN Ji-jing, MAO Jing-jing , SU Li-fang. Induction ofApoptosis in the ImmatureMouse Testes by aMixture ofMelamine and CyanuricAcid[J]. >Journal of Integrative Agriculture, 2012, 12(12): 2058-2066.
[12] WANG Hui, JIA Gang, CHEN Zheng-li, HUANG Lan, WU Cai-mei, WANG Kang-ning. The Effect of Glycyl-Glutamine Dipeptide Concentration on Enzyme Activity,Cell Proliferation and Apoptosis of Jejunal Tissues from Weaned Piglets[J]. >Journal of Integrative Agriculture, 2011, 10(7): 1088-1095.
[13] CUI Mao-sheng, LIU Zhen-xing, WANG Xian-long, ZHANG Jing, WU Yi, HAN Guo-cai , ZENG Shen-ming . Relationship Between Differential Expression of Bax and Bcl-2 Genes and Developmental Differences of Porcine Parthenotes Cultured in PZM-3 and NCSU-23 [J]. >Journal of Integrative Agriculture, 2011, 10(11): 1772-1780.
No Suggested Reading articles found!