Influence of focal brain damage on autoimmune disease of the central nervous system
Influence of focal brain damage on autoimmune disease of the central nervous system
The following hypotheses will be tested: that two major factors, intrinsic to the CNS, are pivotal in the enhancement of autoimmune inflammation induced by brain injury. These two factors are (a) reactions of cells within the CNS itself and (b) the spread of inflammatory mediators through the extracellular compartment.
Two sets of experiments were performed: I. Cryolesion-EAE. EAE was induced in 58 rats, 36 of which received a cryolesion at 8 d.p.i., 22 rats had EAE-only. 12 normal rats received a cryolesion only. Animals were killed between 8 and 40 d.p.i. or 30 minutes and 22 days post cryolesion II. Intracerebral injection of proinflammatory cytokines. 16 EAE rats received an intracerebral injection of rTNF-α, rIFN-γ, saline or a needle wound only. 14 normal rats served as controls. Animals were killed 3 and 5 days after injection. Formalin fixed paraffin sections of brain and spinal cord from both studies were stained with H&E, KB and by immunocytochemistry for quantitative and qualitative analysis.
Results: 1. The number of cerebral EAE lesions and the level of MHC class II antigen expression at 11-15 d.p.i. were significantly enhanced by a cryolesion (p<0.05) but not at 20-40 d.p.i.; 2. A cryolesion changed the pattern of distribution of inflammation in the cerebral hemispheres in EAE; 3. Microglial activation showed functional and morphological heterogeneity associated with the cryolesion, around vessels, within white matter and associated with synaptic stripping of neurons; 4. Axonal damage was associated with EAE lesions; 5. Pro-inflammatory cytokines rTNF-α and rIFN-γ upregulated the inflammatory responses in cerebral EAE and mimicked cryolesion-EAE.
Conclusions: Spread of local inflammatory factors and stimulation of neural activity both play a significant role in the acceleration and enhancement of cerebral EAE following brain injury. This may have significance for the pathogenesis of multiple sclerosis in man.
University of Southampton
Sun, Dong
31f20fcf-e383-441d-8a91-41f96adce55b
1999
Sun, Dong
31f20fcf-e383-441d-8a91-41f96adce55b
Sun, Dong
(1999)
Influence of focal brain damage on autoimmune disease of the central nervous system.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The following hypotheses will be tested: that two major factors, intrinsic to the CNS, are pivotal in the enhancement of autoimmune inflammation induced by brain injury. These two factors are (a) reactions of cells within the CNS itself and (b) the spread of inflammatory mediators through the extracellular compartment.
Two sets of experiments were performed: I. Cryolesion-EAE. EAE was induced in 58 rats, 36 of which received a cryolesion at 8 d.p.i., 22 rats had EAE-only. 12 normal rats received a cryolesion only. Animals were killed between 8 and 40 d.p.i. or 30 minutes and 22 days post cryolesion II. Intracerebral injection of proinflammatory cytokines. 16 EAE rats received an intracerebral injection of rTNF-α, rIFN-γ, saline or a needle wound only. 14 normal rats served as controls. Animals were killed 3 and 5 days after injection. Formalin fixed paraffin sections of brain and spinal cord from both studies were stained with H&E, KB and by immunocytochemistry for quantitative and qualitative analysis.
Results: 1. The number of cerebral EAE lesions and the level of MHC class II antigen expression at 11-15 d.p.i. were significantly enhanced by a cryolesion (p<0.05) but not at 20-40 d.p.i.; 2. A cryolesion changed the pattern of distribution of inflammation in the cerebral hemispheres in EAE; 3. Microglial activation showed functional and morphological heterogeneity associated with the cryolesion, around vessels, within white matter and associated with synaptic stripping of neurons; 4. Axonal damage was associated with EAE lesions; 5. Pro-inflammatory cytokines rTNF-α and rIFN-γ upregulated the inflammatory responses in cerebral EAE and mimicked cryolesion-EAE.
Conclusions: Spread of local inflammatory factors and stimulation of neural activity both play a significant role in the acceleration and enhancement of cerebral EAE following brain injury. This may have significance for the pathogenesis of multiple sclerosis in man.
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Published date: 1999
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Local EPrints ID: 463740
URI: http://eprints.soton.ac.uk/id/eprint/463740
PURE UUID: 41de8dcf-1bc1-46e1-96fa-d5128ba47d16
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Date deposited: 04 Jul 2022 20:56
Last modified: 04 Jul 2022 20:56
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Author:
Dong Sun
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