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Cytokine-induced acute inflammation in the brain and spinal cord

Cytokine-induced acute inflammation in the brain and spinal cord
Cytokine-induced acute inflammation in the brain and spinal cord
Different compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNF[alpha] or rrIL-1[beta] into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNF[alpha] failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNF[alpha] resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1[beta] into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1[beta] into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries.
0022-3069
245-254
Schnell, L.
a5ce7407-47f9-4ce0-91af-e27eb84bd4a3
Fearn, S.
29233c91-d325-46b7-81a2-c057c815d3a2
Schwab, M.E.
29921f9a-0d99-426b-a58c-f1f972344644
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf
Schnell, L.
a5ce7407-47f9-4ce0-91af-e27eb84bd4a3
Fearn, S.
29233c91-d325-46b7-81a2-c057c815d3a2
Schwab, M.E.
29921f9a-0d99-426b-a58c-f1f972344644
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf

Schnell, L., Fearn, S., Schwab, M.E., Perry, V.H. and Anthony, D.C. (1999) Cytokine-induced acute inflammation in the brain and spinal cord. Journal of Neuropathology & Experimental Neurology, 58 (3), 245-254.

Record type: Article

Abstract

Different compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNF[alpha] or rrIL-1[beta] into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNF[alpha] failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNF[alpha] resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1[beta] into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1[beta] into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries.

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More information

Published date: March 1999
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 56713
URI: http://eprints.soton.ac.uk/id/eprint/56713
ISSN: 0022-3069
PURE UUID: 3888961b-a077-48f1-b426-01d523feda92

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Date deposited: 22 Aug 2008
Last modified: 22 Apr 2024 16:34

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Contributors

Author: L. Schnell
Author: S. Fearn
Author: M.E. Schwab
Author: V.H. Perry
Author: D.C. Anthony

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