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Multiple sclerosis can be pathologically defined as the presence of distributed glial scars (or sclerosis) in the central nervous system.〔Dutta R1, Trapp BD. Pathology and definition of multiple sclerosis. Rev Prat. 2006 Jun 30;56(12):1293-8.〕 These glial scars are the remainings of previous demyelinating inflammatory lesions (encephalomyelitis disseminata) in the CNS white matter of a person, showing special characteristics, like for example confluent instead of perivenous demyelination.〔Nathan P. Young , Brian G. Weinshenker , Joseph E. Parisi , B. Scheithauer , C. Giannini , Shanu F. Roemer , Kristine M. Thomsen , Jayawant N. Mandrekar , Bradley J. Erickson , Claudia F. Lucchinetti, Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis, Brain 2010, DOI: http://dx.doi.org/10.1093/brain/awp321 333-348 First published online: 3 February 2010〕 Currently the term "multiple sclerosis" refers not only to the presence of the scars, but also to the several processes and underlying conditions that contribute to their development. Specially important in the lesion development are some white matter areas, which are abnormal under MRI, named NAWM (normal appearing white matter) because its where the lesions appear. Also important are NAGM (gray matter areas) and grey matter lesions. Confluent subpial cortical lesions are the most specific finding for MS, being exclusively present in MS patients.〔Hans Lassmann. Multiple sclerosis: Lessons from molecular neuropathology. Experimental Neurology, Volume 262, Part A, December 2014, Pages 2–7, doi:10.1016/j.expneurol.2013.12.003 ()〕 and maybe the initial trigger.〔B.F.Gh. Popescu, MD, PhD, R.F. Bunyan, MD, J.E. Parisi, MD, R.M. Ransohoff, MD and C.F. Lucchinetti, A case of multiple sclerosis presenting with inflammatory cortical demyelination. Neurology May 17, 2011 vol. 76 no. 20 1705-1710. doi: 10.1212/WNL.0b013e31821a44f1〕 Though this feature can only be detected during an autopsy〔Alexandra Kutzelnigg et al. Widespread Demyelination in the Cerebellar Cortex in Multiple Sclerosis, Brain Pathology, Volume 17, Issue 1, pages 38–44, January 2007, DOI: 10.1111/j.1750-3639.2006.00041.x〕 there are some subrogate markers under study〔Absinta M et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015 Apr 17. pii: 10.1212/WNL.0000000000001587〕 ==Demyelination process and specific areas of damage== Damage occurs in two phases. First some MRI-abnormal areas with hidden damage appear in the brain and spine (NAWM, NAGM, DAWM), followed later by leaks in the blood–brain barrier where immune cells infiltrate causing the known demyelination. According to the view of most researchers, a special subset of lymphocytes, called T helper cells, specifically Th1 and Th17, play a key role in the development of the lesion. A protein called Interleukin 12 is responsible for the differentiation of naive T cells into inflammatory T cells. An over production of this protein is what causes the increased inflammation in MS patients.〔http://wwwchem.csustan.edu/chem4400/sjbr/corey02.htm〕 Under normal circumstances, these lymphocytes can distinguish between self and non-self. However, in a person with MS, these cells recognize healthy parts of the central nervous system as foreign and attack them as if they were an invading virus, triggering inflammatory processes and stimulating other immune cells and soluble factors like cytokines and antibodies. Many of the myelin-recognizing T cells belong to a terminally differentiated subset called co-stimulation-independent effector-memory T cells. Recently other type of immune cells, B Cells, have been also implicated in the pathogenesis of MS and in the degeneration of the axons.〔(Cause of nerve fiber damage in multiple sclerosis identified )〕 and the oligodendrocytes. The axons themselves can also be damaged by the attacks. Often, the brain is able to compensate for some of this damage, due to an ability called neuroplasticity. MS symptoms develop as the cumulative result of multiple lesions in the brain and spinal cord. This is why symptoms can vary greatly between different individuals, depending on where their lesions occur. Repair processes, called remyelination, also play an important role in MS. Remyelination is one of the reasons why, especially in early phases of the disease, symptoms tend to decrease or disappear temporarily. Nevertheless, nerve damage and irreversible loss of neurons occur early in MS. The oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. However, the central nervous system can recruit oligodendrocyte stem cells capable of proliferation and migration and differentiation into mature myelinating oligodendrocytes. The newly formed myelin sheaths are thinner and often not as effective as the original ones. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons. These scars are the so-called "scleroses" that define the condition. They are named glial scars because they are produced by glial cells, mainly astrocytes, and their presence prevents remyelination. Therefore, there is research ongoing to prevent their formation. Under laboratory conditions, stem cells are quite capable of proliferating and differentiating into remyelinating oligodendrocytes; it is therefore suspected that inflammatory conditions or axonal damage somehow inhibit stem cell proliferation and differentiation in affected areas 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Pathology of multiple sclerosis」の詳細全文を読む スポンサード リンク
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