INVESTIGADORES
PODHAJCER Osvaldo Luis
artículos
Título:
Reversible demyelination, blood brain barrier breackdown and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain
Autor/es:
FERRARI CC; DEPINO AM; PRADA F; MURAZO N; CAMPBELL S; PODHAJCER OL; PERRY VH; ANTHONY DC; PITOSSI FJ
Revista:
AMERICAN JOURNAL OF PATHOLOGY
Editorial:
AMER SOC INVESTIGATIVE PATHOLOGY, INC
Referencias:
Año: 2004 vol. 165 p. 1827 - 1837
ISSN:
0002-9440
Resumen:
Interleukin-1_ (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.