Evidence for involvement of the neural pathway containing the peripheral vagus nerve, medullary visceral zone and central amygdaloid nucleus in neuroimmunomodulation.

It is now evident that a bidirectional communication network exists between the central nervous system (CNS) and immune system (IS). However, the way in which the IS passes inform to the brain is not quite clear.In the present study, one of the neural pathways involved in the cytokine-to-brain communication was investigated in the rat. This pathway starts at the vagal nerve projecting to the medullary visceral zone (MVZ), an arc-shape band from the dorsomedial to ventrolateral area in the middle-caudal segment of the medulla oblongata, and terminates at the central amygdaloid nucleus (Ce) which receives projections from large catecholaminergic neurons in the MVZ. Animals were randomly divided into two experimental groups. Triple-labeling was used in Group I animals to combine wheat germ aggulutinin-conjugated horseradish peroxidase (WGA-HRP) retrograde tracing with anti-Fos and anti-tyrosine hydroxylase (TH) immunostaining. WGA-RP was stereotaxically injected into the unilateral Ce of the animals and, after a survival period of 48 h, intraperitoneal (IP) injection of lipopolysaccharide (LPS) was performed. Seven kinds of labeled neurons were observed in the MVZ, namely, HRP-, Fos- or TH-singly-labeled neurons; Fos/HRP-, Fos/TH- or HRP/TH-doubly-labeled neurons; and Fos/HRP/TH-triply-labeled neurons. As for Group II animals, bilateral subdiaphragmatic vagotomy (SDV) or sham operation was performed, followed 4 weeks later by IP injection of LPS. The number of Fos-positive neurons within the Ce and MVZ was significantly lower (P<0.01) in rats having SDV when compared with those receiving sham operation. Our results suggest that part of the peripheral immune information can be conveyed through the vagus to the catecholaminergic neurons in the MVZ, where it is transported to the Ce. The MVZ is a neural relay station in the immune-to-brain communication and might play a significant role in neuroimmuno-modulation via the vagus-MVZ-Ce pathway.

Characterization of extracellular matrix in non-Hodgkin's lymphomas.

Basement membrane proteins laminin, type IV collagen and aminoterminal propeptide of type III collagen (type III pN-collagen) are important components of extracellular matrix of normal lymph nodes; they are present in reticular fibres and in the walls of blood vessels and sinuses. We have studied the distribution of these proteins in 45 cases of non-Hodgkin's lymphomas representing different types of Kiel classification. Light microscopic immunohistochemistry was used on sections from formalin fixed, paraffin embedded biopsy specimens. Reticular cells were identified by using antibodies against S-100 protein, a marker for dendritic and interdigitating reticulum cells, and against cystatin A for the demonstration of follicular dendritic reticulum cells. The findings of the immunohistochemical stainings were generally similar in the different lymphoma types. Thus the method for the demonstration of extracellular matrix proteins could not give obvious aid for lymphoma classification. BM stainings proved to be efficient in the demonstration of sinuses. Marginal and medullary sinuses of the nodal cases were either totally or partly spared and open also in the cases in which there was extracapsular growth. The fibre content was variable, but generally the distribution of all the three extracellular matrix proteins was comparable with each other and mainly corresponded with the pattern seen in conventional Gomori's reticulin stain. This also holds for the tumor tissue infiltrated through the capsule and for extranodal cases. Areas of sclerosis of some cases contained only type III pN-collagen. Reticular fibres were at places seen to be closely associated with cells of spindle or dendritic shape. A few reticulum cells could be found to show cytoplasmic staining for laminin, type IV collagen and type III pN collagen. This finding suggests that the cells are synthetizing these proteins. The amount of cells staining for cystatin A or S-100 protein did not generally correlate with the amount of fibres, and most of the stained cells were not closely associated with fibres. The results show that in non-Hodgkin's lymphomas basement membrane proteins and type III pN-collagen are important components of reticular fibres. Results also indirectly support the main role of fibroblastic reticulum cells in the production of the fibres.

Somatostatin-like immunoreactivity in the midbrain of the cat.

Somatostatin (SS) immunoreactivity was localized in cat brain sections with an immunoperoxidase technique. Cell bodies in the midbrain containing SS immunoreactivity were found in the superficial and intermediate gray layers of the superior colliculus, the interpeduncular nucleus, the raphe, the inferior colliculus and nucleus of its brachium, the nucleus of the optic tract, and the lateral tegmental field. Additional positive neurons were seen in the parabigeminal nucleus and in the dorsal periaqueductal gray in kitten material. Immunoreactive fibers were observed in the periaqueductal gray and in the midbrain tegmentum, with particularly dense labeling just dorsal to the substantia nigra and in the parabrachial nuclei. This is the first report of the distribution of SS immunoreactivity in the midbrain of the cat. It is concluded that somatostatin has a distribution compatible with a role as a major neurotransmitter/neuromodulator within certain midbrain nuclei, especially the interpeduncular nucleus and the superior colliculus.