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DORFMAN Damian

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Título:

Critical Role of Monocyte Recruitment in Optic Nerve Damage Induced by Experimental Optic Neuritis

Autor/es:

ARANDA, MARCOS L.; GUERRIERI, DIEGO; PIÑERO, GONZALO; GONZÁLEZ FLEITAS, MARÍA F.; ALTSCHULER, FLORENCIA; DIEGUEZ, HERNÁN H.; KELLER SARMIENTO, MARÍA I.; CHIANELLI, MÓNICA S.; SANDE, PABLO H.; DORFMAN, DAMIÁN; ROSENSTEIN, RUTH E.

Revista:

MOLECULAR NEUROBIOLOGY

Editorial:

HUMANA PRESS INC

Referencias:

Lugar: Oregon; Año: 2019

ISSN:

0893-7648

Resumen:

Neuroinflammatorydiseases are characterized by blood-brain barrier disruption (BBB) andleukocyte infiltration. We investigated the involvement of monocyte recruitmentin visual pathway damage provoked by primary optic neuritis (ON) induced by amicroinjection of bacterial lipopolysaccharide (LPS) into the optic nerve frommale Wistar rats. Increased Evans blue extravasation and cellularity wereobserved at 6 h post-LPS injection. In WT-GFPþ/WT chimeric rat opticnerves, the presence of GFP(+) neutrophils and GFP(+) monocytes, and inwild-type rat optic nerves, an increase in CD11b + CD45 low and CD11b + CD45high cell number, were observed at 24 h post-LPS. Gamma-irradiation didnot affect the increase in BBB permeability, but significantly lessened thedecrease in pupil light reflex (PLR), and retinal ganglion cell (RGC) numberinduced by LPS. At 6 h post-LPS, an increase in chemokine (C-C motif)ligand 2 (CCL2) immunoreactivity co-localized with neutrophils (but notmicroglia/macrophages or astrocytes) was observed, while at 24 hpost-injection, an increase in Iba-1-immunoreactivity and its co-localizationwith CCL2 became evident. The co-injection of LPS with bindarit (a CCL2synthesis inhibitor) lessened the effect of LPS on PLR, and RGC loss. Thetreatment with etoposide or gadolinium chloride that significantly decreasedperipheral monocyte (but not neutrophil or lymphocyte) percentage decreased theeffect of LPS on PLR, and RGC number. Moreover, a negative correlation betweenPRL and monocyte (but not lymphocyte or neutrophil) percentage was observed at7 days post-LPS. Taken together, these results support that monocytes arekey players in the initial events that take place during primary ON.

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