In postnatal tissues, angiogenesis occurs in nontumoral conditions on appropriate stimuli. In the nervous tissue, hypoxia, neural graft, increased neural function, and synaptic activity are associated with neoangiogenesis. We have investigated the occurrence of neoangiogenesis in the superior cervical ganglia (scg) of newborn rats treated for 8 -21 days with 6-hydroxy-dopamine (6-OHDA), nerve growth factor (NGF), or 6-OHDA ؉ NGF. The two latter treatments induced a significant increase in scg size. However, the increase after combined treatment far exceeded that of NGF alone. Similarly, histological and histochemical analysis revealed neuronal hypertrophy and endothelial cell hyperplasia associated with stromal hypertrophy (as described by laminin immunostaining) and increased vascular bed (as revealed by platelet͞endothelial cell adhesion molecule-1 immunostaining) in 6-OHDA ؉ NGF-treated pups. NGF, either alone or associated with 6-OHDA, also induced a significant up-regulation of NADPH diaphorase, neuronal nitric oxide synthase, and vascular endothelial growth factor expression in scg neurons. The present investigation suggests that the increase of scg size induced by NGF and 6-OHDA ؉ NGF is associated with neoangiogenesis, and that the induction of vasoactive and angiogenic factors in neurons represents a further and previously undisclosed effect of NGF.

Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor ␣ receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.neuroprotection ͉ multiple sclerosis ͉ oligodendrocyte precursor cells ͉ axonal pathology ͉ rat M ultiple sclerosis (MS) is a disorder of the central nervous system (CNS) that manifests as acute focal inflammatory demyelination with limited remyelination, usually culminating in chronic multifocal sclerotic plaques (1). Early axonal injury and loss followed by neuron distress (2) and death (3) occur in MS (4-6), accounting for brain and spinal cord atrophy. Irreversible axonal damage is an essential cause of nonremitting sensory, motor, and cognitive disabilities in MS (7). Although remyelination occurs in most experimental models of demyelination, this beneficial process is undoubtedly inadequate in MS. The reasons for this inadequacy are unknown, also because the oligodendrocyte precursor cells (OPCs), the cell population that is considered to be the most important source of remyelinating oligodendrocytes in the adult CNS (8-10), are present in early (fresh) demyelinating lesions in MS (11, 12).There are many possible speculative explanations for remyelination failure in MS (9, 10), including quantitatively inadequate recruitment and͞or differentiation of OPCs (13); axons not receptive to remyelination (14); and inappropriate support of growth factors by astrocytes and͞or other inflammatory cells (15), such as the extracellular microenvironment with regard to matrix proteins and adhesion molecules (16).Because the number of oligodendrocytes is greater than before demyelination in early MS, meaning that new oligodendrocytes are generated (17), another possibility is that OPCs are unable to turn into myelinating oligodendrocytes in chronic MS. Thus, extensive studies are under way to identify factors involved in OPC differentiation during remyelination. It is generally accepted that the process of remyelination represents a recapitulation of myelination during development, and so the key factors affecting the developmental maturation of OPCs into myelinating oligodendrocytes also should favor remyelination in the adult CNS. It ...

Remyelination in the adult central nervous system has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that remyelination occurs in multiple sclerosis, the most diffuse demyelinating disease. In this article, we explore the possibility of promoting myelination in experimental allergic encephalomyelitis, a widely used experimental model of multiple sclerosis, by recruiting progenitors and channeling them into oligodendroglial lineage through administration of thyroid hormone (T4). A large number of proliferating cells (BrdUrd uptake and Ki67-IR) and the expression of markers for undifferentiated precursors (nestin) increased in the subventricular zone and spinal cord of experimental allergic encephalomyelitis animals. T4 administration reduces proliferation and nestin-immunoreactivity and up-regulates expression of markers for oligodendrocyte progenitors [polysialylated-neural cell adhesion molecule (PSA-NCAM), O4, A2B5] and mature oligodendrocytes (myelin basic protein) in the spinal cord, olfactory bulb, and subventricular zone. Multiple sclerosis is an inflammatory-autoimmune disease with multiple foci of demyelination in the central nervous system (CNS) in the chronic stage of the disease (1). Although there is evidence of remyelination in different experimental conditions in the adult CNS (2), remyelination attempts observed in early plaques in multiple sclerosis are not followed by repair of the lesion (3). The reason for this is still unknown. A significant number of oligodendrocyte precursor cells were found in early lesions in multiple sclerosis tissue (4, 5), although they were in a relatively quiescent state in chronic lesions (6).One crucial question to be answered in the evaluation of repair potentiality in this demyelinating disease regards the capability of a substantial number of oligodendrocyte precursors to differentiate and remyelinate within the brain and spinal cord. Oligodendrocyte precursors are disseminated within the white and gray matter of the adult CNS, but they also can be generated from stem cells present in different areas of the CNS (2, 7). Consequently, a potentially unlimited number of myelinating cells could be recruited in the adult CNS. Multipotential precursors have been demonstrated in the subventricular zone (SVZ) of the lateral ventricle, the dentate gyrus of the hippocampus (8-10), and the spinal cord (11, 12), where ependymal cells are able to differentiate in vitro into adult cells (13).Therefore, the possibility of recruiting populations of precursor cells to replace degenerating neurons or glial cells through an in vitro or in vivo approach has become very attractive. Our previous results demonstrated that the proliferative rate and expression of nestin, a marker for neuroepithelial cells, is up-regulated in the SVZ (14) during experimental allergic encephalomyelitis (EAE). Moreover, exogenous administration of thyroid hormone in adult rats modifies proliferation and expression of stem cell markers in th...