Normal Adult Central Nervous System Research Articles

Quantitative analysis of vascularization and cytochrome oxidase following fetal transplantation in the contused rat spinal cord.

In the normal adult central nervous system, a coupling between energy consumption and vascular density is well established. Likewise, the survival of fetal neural tissue grafts is highly dependent on the establishment of functional vascular integration with the host. However, to what degree graft vascularization and tissue metabolism influence the normal host response to traumatic injury has not been extensively studied. In the present report, embryonic day 14 fetal spinal cord suspension grafts were made into the lesion epicenter of subchronic (10 days) contusion-injured rats. Three months later, intraspinal transplants were analyzed using correlative cytochrome oxidase histochemistry and vascular morphometric analysis. The same approaches were applied to the host spinal cord and injured, non-transplanted animals in order to determine the ability of a graft to alter the level of post-injury vascularization and/or metabolism. In general, graft vascular density was increased over that measured in normal or injured gray matter. Vascular density in gray matter near the host/graft interface was markedly increased when compared to either gray matter of the same spinal level in injured non-grafted animals or normal control spinal gray matter. Vascular changes were not noted in gray matter 3 mm distal to the lesion epicenter (rostral or caudal) in all groups analyzed. Cytochrome oxidase was up-regulated at this time in the graft and gray matter at the host/graft interfaces when compared to either gray matter of the same spinal level in injured, non-grafted animals or that of uninjured controls. These data indicate that an intraspinal transplant placed into the contused adult rat spinal cord reaches a metabolic capacity that is likely to be associated with high levels of oxidative metabolism in the well-vascularized graft neuropil. In addition, transplantation chronically alters vascularization and metabolic patterns of adjacent spinal gray matter following contusion injury.

Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin-derived inhibitors of neurite growth.

Axon growth inhibitory proteins associated with central nervous system (CNS) myelin are responsible in part for the absence of long distance axon regeneration in the adult mammalian CNS. We have recently reported that myelin-associated glycoprotein (MAG), which is also present in peripheral nerves, is a potent inhibitor of neurite growth. This was surprising given the robust regenerative capacity of peripheral nerves. We now provide evidence that myelin purified from peripheral nerve also has neurite growth inhibitory activity. However, this activity can be masked by laminin, which is a constituent of the Schwann cell basal lamina. We also report that laminin, which is largely absent from the normal adult mammalian CNS, when added to purified CNS myelin, can override the neurite growth inhibitory activity in CNS myelin. These results have important implications for the development of strategies to foster axon regeneration in the adult mammalian CNS where multiple growth inhibitors exist.

Cell type-specific control of human neuronectin secretion by polypeptide mediators and phorbol ester.

Neuronectin (NEC1) is a human extracellular matrix (ECM) protein expressed with a unique rostrocaudal pattern in white matter of the normal adult central nervous system. In addition, NEC1 is expressed in normal fetal and adult smooth muscle, along certain epithelial-mesenchymal junctions, and transiently in developing fetal cartilage. Region-specific induction of NEC1 is found in dermal wounds and in the reactive stroma of actinic keratoses, psoriatic skin lesions, and a range of malignant tumors. One explanation for these diverse tissue patterns is that cells capable of producing NEC1 are widely distributed in neural and mesenchymal tissues, but they become NEC1 producers only when induced by region-specific differentiation signals. In this study, we used cultured human cells to show that several regulatory polypeptides, including fibroblast growth factors, tumor necrosis factor, platelet-derived growth factor, nerve growth factor, and transforming growth factor-beta (TGF-beta), as well as 12-O-tetradecanoyl phorbol-13-acetate (TPA), modulate NEC1 secretion, with distinct patterns of inducing and inhibitory activities in different neural and mesenchymal cell types. TPA and TGF-beta act both as inducers and inhibitors of NEC1 secretion, depending on the target cell. These effects are specific for NEC1 and are not seen for several other secreted and membrane proteins studied. We suggest that NEC1 expression comes under different modes of extrinsic control in different cell lineages and in response to tissue injury and neoplasia.

Immunohistochemical study on neuroglia identified by the monoclonal antibody against a macrophage differentiation antigen (mac-1)

We have studied frozen sections of the developing and adult mouse central nervous system (CNS), with or without cold lesions, by immunohistochemical and histochemical methods. Using a monoclonal antibody against a macrophage differentiation antigen (Mac-1), we have shown that some neuroglia in the white matter of adult mice stained positively. In the developing CNS, with or without cold lesioning, Mac-1-positive glia were not detected. In the normal adult CNS, a small number of glia in the white matter stained faintly. After cold injury, the number of Mac-1-positive glia and their staining intensity increased for several months. Mac-1-positive glia were always negative for glial fibrillary acidic protein (GFA). Their morphology and distribution were similar to those of nucleoside diphosphatase-positive cells. Considering that the phagocytic activity of glia increases after injury to the CNS (Trachtenberg 1983) and that Mac-1 has been reported to be associated with the complement receptor (Beller et al. 1982), Mac-1-positive glia may play a role in phagocytosis in the damaged CNS.

Are Resting and/or Reactive Microglia Macrophages?

According to recent submicroscopic, cytokinetic, and functional (particularly cytoimmunologic) investigations, no relationship exists between «resting» microglia (the small argyrophilic cells appearing in undamaged brain tissue, first described by RIO HORTEGA) and «reactive» microglia (the argyrophilic cells appearing under pathologic conditions). While «resting» microglia are apparently cells of neuro-ectodermal origin, all observations tend to indicate that «reactive» microglia are derived from extravasated blood monocytes and should be called brain macrophages. In the intact brain parenchyma, no macrophages are demonstrable. Free subarachnoidal cells in the cerebrospinal fluid (CSF), perivascular cells, and epiplexus and/or supraependymal cells in the CSF-containing spaces of the normal central nervous system are cells of the mononuclear phagocyte system and must be considered as CSF macrophages. According to rough estimates, the normal adult central nervous system contains a maximum of 280,000 CSF macrophages.