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Neuroinflammation induced by intracerebroventricular injection of microbial neuraminidase.

Granados-Durán P, López-Ávalos MD, Grondona JM, Gómez-Roldán Mdel C, Cifuentes M, Pérez-Martín M, Alvarez M, Rodríguez de Fonseca F, Fernández-Llebrez P - Front Med (Lausanne) (2015)

Bottom Line: The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes.Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans.Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Ciencias, Universidad de Málaga , Málaga , Spain.

ABSTRACT
In the present paper, we describe the facts that took place in the rat brain after a single injection of the enzyme neuraminidase from Clostridium perfringens into the right lateral ventricle. After injection, it diffused through the cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and about 400 μm into the periventricular brain parenchyma. The expression of ICAM1 in the endothelial cells of the periventricular vessels, IBA1 in microglia, and GFAP in astrocytes notably increased in the regions reached by the injected neuraminidase. The subependymal microglia and the ventricular macrophages begun to express IL1β and some appeared to cross the ependymal layer. After about 4 h of the injection, leukocytes migrated from large venules of the affected choroid plexus, the meninges and the local subependyma, and infiltrated the brain. The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes. Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans. Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content.

No MeSH data available.


Related in: MedlinePlus

(A) IBA1-positive epiplexus and subependymal cells (arrowheads) in a vehicle-injected specimen sacrificed immediately after the injection. (B) Detail of the striatal (st) side of the injected lateral ventricle (i) near the inferior sulcus of the lateral ventricle 2 h after the injection. Note IBA1-positive cells over, beneath and among the ependymal cells (arrow and inset). (C) Two hours after the injection of NA, scattered IL1β-positive cells occurred inside (arrow) and outside the choroid plexus (cp) as well as in the subependyma (arrowhead) of the injected ventricle. (D) Detail of IL1β-stained cells in the subependyma (arrowhead) and crossing the ependymal wall (arrow) of the third ventricle (IIIv) 4 h after the injection of NA. (E,F) Double immunofluorescence with anti-IBA1 (red) and anti-IL1β (green). Double-stained cells appear in the ventricle and the subependyma (arrowheads, and merge detailed in the inset of (F) showing a double-stained subependymal cell). Many IBA1-positive cells in the brain parenchyma were not immunoreactive to IL1β [arrow in (E)]. cp, choroid plexus; sf, septum-fimbria; sm, stria medullaris; (i), injected lateral ventricle; st, striatal wall of the lateral ventricle; f, fornix; IIIv, third ventricle.
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Figure 3: (A) IBA1-positive epiplexus and subependymal cells (arrowheads) in a vehicle-injected specimen sacrificed immediately after the injection. (B) Detail of the striatal (st) side of the injected lateral ventricle (i) near the inferior sulcus of the lateral ventricle 2 h after the injection. Note IBA1-positive cells over, beneath and among the ependymal cells (arrow and inset). (C) Two hours after the injection of NA, scattered IL1β-positive cells occurred inside (arrow) and outside the choroid plexus (cp) as well as in the subependyma (arrowhead) of the injected ventricle. (D) Detail of IL1β-stained cells in the subependyma (arrowhead) and crossing the ependymal wall (arrow) of the third ventricle (IIIv) 4 h after the injection of NA. (E,F) Double immunofluorescence with anti-IBA1 (red) and anti-IL1β (green). Double-stained cells appear in the ventricle and the subependyma (arrowheads, and merge detailed in the inset of (F) showing a double-stained subependymal cell). Many IBA1-positive cells in the brain parenchyma were not immunoreactive to IL1β [arrow in (E)]. cp, choroid plexus; sf, septum-fimbria; sm, stria medullaris; (i), injected lateral ventricle; st, striatal wall of the lateral ventricle; f, fornix; IIIv, third ventricle.

Mentions: In control rats, IBA1 stained epiplexus cells in the choroid plexus and very few subependymal microglial cells (Figure 3A). In the experimental animals, a quite striking observation was that some IBA1-positive cells beneath the ependyma, seemed to penetrate between the ependymal cells even before the onset of blood cell infiltration (Figure 3B and inset). In similar locations, IL1β-positive cells could be found at early times after NA administration (Figures 3C,D). Moreover, double immunostaining demonstrated the existence of cells that were positive to both IBA1 and IL1β (Figures 3E,F).


Neuroinflammation induced by intracerebroventricular injection of microbial neuraminidase.

Granados-Durán P, López-Ávalos MD, Grondona JM, Gómez-Roldán Mdel C, Cifuentes M, Pérez-Martín M, Alvarez M, Rodríguez de Fonseca F, Fernández-Llebrez P - Front Med (Lausanne) (2015)

(A) IBA1-positive epiplexus and subependymal cells (arrowheads) in a vehicle-injected specimen sacrificed immediately after the injection. (B) Detail of the striatal (st) side of the injected lateral ventricle (i) near the inferior sulcus of the lateral ventricle 2 h after the injection. Note IBA1-positive cells over, beneath and among the ependymal cells (arrow and inset). (C) Two hours after the injection of NA, scattered IL1β-positive cells occurred inside (arrow) and outside the choroid plexus (cp) as well as in the subependyma (arrowhead) of the injected ventricle. (D) Detail of IL1β-stained cells in the subependyma (arrowhead) and crossing the ependymal wall (arrow) of the third ventricle (IIIv) 4 h after the injection of NA. (E,F) Double immunofluorescence with anti-IBA1 (red) and anti-IL1β (green). Double-stained cells appear in the ventricle and the subependyma (arrowheads, and merge detailed in the inset of (F) showing a double-stained subependymal cell). Many IBA1-positive cells in the brain parenchyma were not immunoreactive to IL1β [arrow in (E)]. cp, choroid plexus; sf, septum-fimbria; sm, stria medullaris; (i), injected lateral ventricle; st, striatal wall of the lateral ventricle; f, fornix; IIIv, third ventricle.
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Related In: Results  -  Collection

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Figure 3: (A) IBA1-positive epiplexus and subependymal cells (arrowheads) in a vehicle-injected specimen sacrificed immediately after the injection. (B) Detail of the striatal (st) side of the injected lateral ventricle (i) near the inferior sulcus of the lateral ventricle 2 h after the injection. Note IBA1-positive cells over, beneath and among the ependymal cells (arrow and inset). (C) Two hours after the injection of NA, scattered IL1β-positive cells occurred inside (arrow) and outside the choroid plexus (cp) as well as in the subependyma (arrowhead) of the injected ventricle. (D) Detail of IL1β-stained cells in the subependyma (arrowhead) and crossing the ependymal wall (arrow) of the third ventricle (IIIv) 4 h after the injection of NA. (E,F) Double immunofluorescence with anti-IBA1 (red) and anti-IL1β (green). Double-stained cells appear in the ventricle and the subependyma (arrowheads, and merge detailed in the inset of (F) showing a double-stained subependymal cell). Many IBA1-positive cells in the brain parenchyma were not immunoreactive to IL1β [arrow in (E)]. cp, choroid plexus; sf, septum-fimbria; sm, stria medullaris; (i), injected lateral ventricle; st, striatal wall of the lateral ventricle; f, fornix; IIIv, third ventricle.
Mentions: In control rats, IBA1 stained epiplexus cells in the choroid plexus and very few subependymal microglial cells (Figure 3A). In the experimental animals, a quite striking observation was that some IBA1-positive cells beneath the ependyma, seemed to penetrate between the ependymal cells even before the onset of blood cell infiltration (Figure 3B and inset). In similar locations, IL1β-positive cells could be found at early times after NA administration (Figures 3C,D). Moreover, double immunostaining demonstrated the existence of cells that were positive to both IBA1 and IL1β (Figures 3E,F).

Bottom Line: The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes.Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans.Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Ciencias, Universidad de Málaga , Málaga , Spain.

ABSTRACT
In the present paper, we describe the facts that took place in the rat brain after a single injection of the enzyme neuraminidase from Clostridium perfringens into the right lateral ventricle. After injection, it diffused through the cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and about 400 μm into the periventricular brain parenchyma. The expression of ICAM1 in the endothelial cells of the periventricular vessels, IBA1 in microglia, and GFAP in astrocytes notably increased in the regions reached by the injected neuraminidase. The subependymal microglia and the ventricular macrophages begun to express IL1β and some appeared to cross the ependymal layer. After about 4 h of the injection, leukocytes migrated from large venules of the affected choroid plexus, the meninges and the local subependyma, and infiltrated the brain. The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes. Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans. Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content.

No MeSH data available.


Related in: MedlinePlus