FOCAL BRAIN-DAMAGE ENHANCES EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN BRAIN AND SPINAL-CORD

被引:36
作者
PHILLIPS, MJ [1 ]
WELLER, RO [1 ]
KIDA, S [1 ]
IANNOTTI, F [1 ]
机构
[1] SOUTHAMPTON GEN HOSP,SCH MED,DEPT PATHOL NEUROPATHOL,SOUTHAMPTON SO16 6YD,HANTS,ENGLAND
关键词
CRYOLESION; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE); MICROGLIA; MHC CLASS II; MULTIPLE SCLEROSIS;
D O I
10.1111/j.1365-2990.1995.tb01050.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The immunological basis of multiple sclerosis (MS) is well recognized but the factors inducing MS lesions are unclear. In this study, we test the hypothesis that focal brain injury, inflicted during the pre-clinical stages of experimental allergic encephalomyelitis (EAE), will enhance the severity of immunological damage in the cerebral hemispheres and spinal cord. Acute EAE was induced in 30 Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant. A cryolesion to the surface of the left cerebral hemisphere was induced at 3 days (n=6) or 8 days (n=10) postinoculation (p.i.) and animals were killed at 15 days p.i. Control animals were EAE only (n=9), cryolesion only (n=4), EAE and sham cryolesion (n=5) and normal animals (n=3). Brain and spinal cord were stained by immunocytochemistry using W3/13 (T-lymphocytes) OX6 (MHC Class II) and GFAP (astrocytes) antibodies. The results showed a 2-fold increase in the number of EAE lesions in the brain with significant and widespread increase of MHC Class II antigen expression by microglia, in the cryolesion EAE 8 days p.i when compared with EAE only animals. The pattern of enhancement suggests that it is due to (i) local spread of tissue or serum factors from the cryolesion; (ii) neural factors affecting remote regions of the CNS; (iii) stimulation of the immune system which may occur due to products of brain injury draining to regional cervical lymph nodes. Investigation of the mechanisms involved may prove fruitful in establishing factors which initiate, aggravate or ameliorate brain damage in multiple sclerosis.
引用
收藏
页码:189 / 200
页数:12
相关论文
共 43 条
[1]   PATHOLOGY, HISTOCHEMISTRY AND IMMUNOCYTOCHEMISTRY OF LESIONS IN ACUTE MULTIPLE-SCLEROSIS [J].
ADAMS, CWM ;
POSTON, RN ;
BUK, SJ .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1989, 92 (2-3) :291-306
[2]   PATHOGENESIS OF MULTIPLE-SCLEROSIS - THE IMMUNE DIATHESIS AND THE ROLE OF VIRUSES [J].
ALLEN, I ;
BRANKIN, B .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1993, 52 (02) :95-105
[3]   TRAUMA AS AN ETIOLOGIC AND AGGRAVATING FACTOR IN MULTIPLE-SCLEROSIS [J].
BAMFORD, CR ;
SIBLEY, WA ;
THIES, C ;
LAGUNA, JF ;
SMITH, MS ;
CLARK, K .
NEUROLOGY, 1981, 31 (10) :1229-1234
[4]   MS - A LOCALIZED IMMUNE DISEASE OF THE CENTRAL NERVOUS-SYSTEM [J].
CALDER, V ;
OWEN, S ;
WATSON, C ;
FELDMANN, M ;
DAVISON, A .
IMMUNOLOGY TODAY, 1989, 10 (03) :99-103
[5]  
CLARK G, 1955, J NEUROPATH EXP NEUR, V14, P433
[6]   REGULATION OF MICROGLIAL FUNCTION BY INTERFERONS [J].
COLTON, CA ;
YAO, J ;
KERI, JE ;
GILBERT, D .
JOURNAL OF NEUROIMMUNOLOGY, 1992, 40 (01) :89-98
[7]   HYPOTHESIS - ANTIGEN-SPECIFIC T-CELLS PRIME CENTRAL-NERVOUS-SYSTEM ENDOTHELIUM FOR RECRUITMENT OF NONSPECIFIC INFLAMMATORY CELLS TO EFFECT AUTOIMMUNE DEMYELINATION [J].
CROSS, AH ;
CANNELLA, B ;
BROSNAN, CF ;
RAINE, CS .
JOURNAL OF NEUROIMMUNOLOGY, 1991, 33 (03) :237-244
[8]   CERVICAL LYMPHATICS, THE BLOOD-BRAIN-BARRIER AND THE IMMUNOREACTIVITY OF THE BRAIN - A NEW VIEW [J].
CSERR, HF ;
KNOPF, PM .
IMMUNOLOGY TODAY, 1992, 13 (12) :507-512
[9]   MICROGLIAL INVOLVEMENT IN EXPERIMENTAL AUTOIMMUNE INFLAMMATION OF THE CENTRAL AND PERIPHERAL NERVOUS-SYSTEM [J].
GEHRMANN, J ;
GOLD, R ;
LININGTON, C ;
LANNESVIEIRA, J ;
WEKERLE, H ;
KREUTZBERG, GW .
GLIA, 1993, 7 (01) :50-59
[10]   MICROGLIAL REACTION IN THE RAT CEREBRAL-CORTEX INDUCED BY CORTICAL SPREADING DEPRESSION [J].
GEHRMANN, J ;
MIES, G ;
BONNEKOH, P ;
BANATI, R ;
IIJIMA, T ;
KREUTZBERG, GW ;
HOSSMANN, KA .
BRAIN PATHOLOGY, 1993, 3 (01) :11-17