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Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage

Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage
Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage
The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.p.i.). The distribution of inflammation and chemokine production in cryolesion-EAE and EAE-only were compared. Inflammation in the brain, measured by immunocytochemistry for T lymphocytes (W3/13) and microglial activation (MHC class II -OX6), was significantly enhanced in cryolesion-EAE 11-15 d.p.i. (p < 0.01-0.05) but by 20-40 d.p.i., equated with EAE-only. Inflammation in cryolesion-EAE related to breakdown of the blood-brain barrier (BBB) at the site of the cryolesion and also to the corticospinal tracts and thalamus, reflecting the afferent and efferent neuronal connections with the cryolesioned cortex. Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha. By 14 d.p.i., the levels of MCP-1 and MCP-5 mRNA equated with EAE-only animals. These results suggest that enhancement and location of autoimmune inflammation in the brain following focal cortical injury initially involve chemokines such as the macrophage chemoattractants MCP-1 and MCP-5, and the activities of afferent and efferent neuronal connections with the site of damage. By analogy, similar factors may modulate or reactivate autoimmune inflammation in MS.
0022-3069
1031-1043
Sun, Dong
31f20fcf-e383-441d-8a91-41f96adce55b
Tani, Marie
65191605-3de8-4adf-bc9b-904a8ba478db
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Krivacic, Kimberly
0efab417-f957-4a93-bd67-c28967dda4f4
Phillips, Marian
3884ebb1-a0c9-4fa5-888a-03c86fac9504
Chernosky, Ann
ac2fd291-58e9-41e1-aa94-647fb289e226
Gill, Pelvender
fbf3e2bd-e5e7-4b96-90e6-4151c50bf40d
Griswold, Katherine J.
58ba4528-c508-4a64-a487-d9f9d2df25fa
Ransohoff, Richard M.
d65ef642-2cfe-4ce5-871c-153362fb7b9e
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Tao, Wei
da82da1e-8381-4a00-914d-0ae491f23bd3
Sun, Dong
31f20fcf-e383-441d-8a91-41f96adce55b
Tani, Marie
65191605-3de8-4adf-bc9b-904a8ba478db
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Krivacic, Kimberly
0efab417-f957-4a93-bd67-c28967dda4f4
Phillips, Marian
3884ebb1-a0c9-4fa5-888a-03c86fac9504
Chernosky, Ann
ac2fd291-58e9-41e1-aa94-647fb289e226
Gill, Pelvender
fbf3e2bd-e5e7-4b96-90e6-4151c50bf40d
Griswold, Katherine J.
58ba4528-c508-4a64-a487-d9f9d2df25fa
Ransohoff, Richard M.
d65ef642-2cfe-4ce5-871c-153362fb7b9e
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Tao, Wei
da82da1e-8381-4a00-914d-0ae491f23bd3

Sun, Dong, Tani, Marie, Newman, Tracey A., Krivacic, Kimberly, Phillips, Marian, Chernosky, Ann, Gill, Pelvender, Griswold, Katherine J., Ransohoff, Richard M., Weller, Roy O. and Tao, Wei (2000) Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage. Journal of Neuropathology and Experimental Neurology, 59 (12), 1031-1043.

Record type: Article

Abstract

The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.p.i.). The distribution of inflammation and chemokine production in cryolesion-EAE and EAE-only were compared. Inflammation in the brain, measured by immunocytochemistry for T lymphocytes (W3/13) and microglial activation (MHC class II -OX6), was significantly enhanced in cryolesion-EAE 11-15 d.p.i. (p < 0.01-0.05) but by 20-40 d.p.i., equated with EAE-only. Inflammation in cryolesion-EAE related to breakdown of the blood-brain barrier (BBB) at the site of the cryolesion and also to the corticospinal tracts and thalamus, reflecting the afferent and efferent neuronal connections with the cryolesioned cortex. Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha. By 14 d.p.i., the levels of MCP-1 and MCP-5 mRNA equated with EAE-only animals. These results suggest that enhancement and location of autoimmune inflammation in the brain following focal cortical injury initially involve chemokines such as the macrophage chemoattractants MCP-1 and MCP-5, and the activities of afferent and efferent neuronal connections with the site of damage. By analogy, similar factors may modulate or reactivate autoimmune inflammation in MS.

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Published date: December 2000

Identifiers

Local EPrints ID: 73389
URI: http://eprints.soton.ac.uk/id/eprint/73389
ISSN: 0022-3069
PURE UUID: 3cc1662a-78fa-4390-b4cc-9da0aa638c7d
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

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Date deposited: 09 Mar 2010
Last modified: 09 Jan 2022 02:51

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Contributors

Author: Dong Sun
Author: Marie Tani
Author: Kimberly Krivacic
Author: Marian Phillips
Author: Ann Chernosky
Author: Pelvender Gill
Author: Katherine J. Griswold
Author: Richard M. Ransohoff
Author: Roy O. Weller
Author: Wei Tao

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