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Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain

Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain
Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain
Interleukin-1ß (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases.
0002-9440
1827-1837
Ferrari, C.C.
7baf83ef-def9-4e05-8872-09591e7776bf
Depino, A.M.
925dd7b3-2940-43ca-8897-ee98f756e05a
Prada, F.
fbbd9a1e-8f08-421a-a84f-2fa1e4b80e2d
Muraro, N.
5c6b28b2-6e66-4a23-91d9-9a6896af9621
Campbell, S.
5e15ce08-4817-4878-8c1d-c6267ed29ed5
Podhajcer, O.
ea39b1cd-dc2e-4aa8-b343-f33a0b2b9bc7
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf
Pitossi, F.J.
4bacb661-ef14-46c0-aba6-9f7fc3030904
Ferrari, C.C.
7baf83ef-def9-4e05-8872-09591e7776bf
Depino, A.M.
925dd7b3-2940-43ca-8897-ee98f756e05a
Prada, F.
fbbd9a1e-8f08-421a-a84f-2fa1e4b80e2d
Muraro, N.
5c6b28b2-6e66-4a23-91d9-9a6896af9621
Campbell, S.
5e15ce08-4817-4878-8c1d-c6267ed29ed5
Podhajcer, O.
ea39b1cd-dc2e-4aa8-b343-f33a0b2b9bc7
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf
Pitossi, F.J.
4bacb661-ef14-46c0-aba6-9f7fc3030904

Ferrari, C.C., Depino, A.M., Prada, F., Muraro, N., Campbell, S., Podhajcer, O., Perry, V.H., Anthony, D.C. and Pitossi, F.J. (2004) Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. The American Journal of Pathology, 165, 1827-1837.

Record type: Article

Abstract

Interleukin-1ß (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases.

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Published date: 1 November 2004

Identifiers

Local EPrints ID: 56325
URI: http://eprints.soton.ac.uk/id/eprint/56325
ISSN: 0002-9440
PURE UUID: 375ad951-77f3-491d-bad4-b48230ff0d03

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Date deposited: 07 Aug 2008
Last modified: 08 Jan 2022 10:05

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Contributors

Author: C.C. Ferrari
Author: A.M. Depino
Author: F. Prada
Author: N. Muraro
Author: S. Campbell
Author: O. Podhajcer
Author: V.H. Perry
Author: D.C. Anthony
Author: F.J. Pitossi

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