Localization In Central Nervous System Research Articles

Central CO2 chemoreception and integrated neural mechanisms of cardiovascular and respiratory control

In this review, we examine why blood pressure (BP) and sympathetic nerve activity (SNA) increase during a rise in central nervous system (CNS) P(CO(2)) (central chemoreceptor stimulation). CNS acidification modifies SNA by two classes of mechanisms. The first one depends on the activation of the central respiratory controller (CRG) and causes the much-emphasized respiratory modulation of the SNA. The CRG probably modulates SNA at several brain stem or spinal locations, but the most important site of interaction seems to be the caudal ventrolateral medulla (CVLM), where unidentified components of the CRG periodically gate the baroreflex. CNS P(CO(2)) also influences sympathetic tone in a CRG-independent manner, and we propose that this process operates differently according to the level of CNS P(CO(2)). In normocapnia and indeed even below the ventilatory recruitment threshold, CNS P(CO(2)) exerts a tonic concentration-dependent excitatory effect on SNA that is plausibly mediated by specialized brain stem chemoreceptors such as the retrotrapezoid nucleus. Abnormally high levels of P(CO(2)) cause an aversive interoceptive awareness in awake individuals and trigger arousal from sleep. These alerting responses presumably activate wake-promoting and/or stress-related pathways such as the orexinergic, noradrenergic, and serotonergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have brainwide projections that contribute to the CO(2)-induced rise in breathing and SNA by facilitating neuronal activity at innumerable CNS locations. In the case of SNA, these sites include the nucleus of the solitary tract, the ventrolateral medulla, and the preganglionic neurons.

Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)‐regulated glial proliferation

Numerous studies have suggested that astrocytes in the central nervous system (CNS) exhibit molecular and functional heterogeneity. In this regard, astroglia from different CNS locations express distinct immune system, and neurotransmitter proteins, have varying levels of gap junction coupling and respond differently to injury. However, the relevance of these differences to human disease is unclear. As brain tumors in children arise in specific CNS locations, we hypothesized that regional astroglial cell heterogeneity might partly underlie the propensity for gliomas to arise in these areas. In this study, we performed high-density RNA microarray profiling on astrocytes from postnatal day 1 optic nerve, cerebellum, brainstem, and neocortex. We showed that astroglia from each region are molecularly distinct, and we were able to develop gene expression patterns that distinguish astroglia, but not neural stem cells, from these different brain regions. We next used these microarray data to determine whether brain tumor suppressor genes were differentially expressed in these distinct populations of astroglia. Interestingly, neurofibromatosis type 1 (NF1) gene expression was decreased at both the RNA and protein levels in neocortical astroglia relative to astroglia from the other brain regions. To determine the functional significance of this finding, we found increased astroglial cell proliferation in optic nerve, brainstem, and cerebellum, but not neocortex, following Nf1 inactivation in vitro and in vivo. These findings provide molecular evidence for CNS astroglial cell heterogeneity, and suggest that differences in tumor suppressor gene expression might contribute to the regional localization of human brain tumors.

Maedi-Visna: the Meningoencephalitis in Naturally Occurring Cases

Lesions were examined at different levels of the central nervous system (CNS) in 64 sheep with natural maedi-visna (MV) meningoencephalitis. All animals showed lesions in more than one of the CNS locations examined; the lesions in the cranial regions were periventricular, while those in the spinal cord affected the white matter funicles. Lesions were found particularly in the cerebellar peduncles (non-suppurative meningoencephalitis), followed by the corpus callosum, hippocampus and thoracic spinal cord. Vascular, infiltrative and malacic histopathological patterns were recognized. One pattern predominated in each section examined, although mixed forms occurred. Vascular lesions occurred with similar frequency at all CNS levels, but infiltrative and malacic lesions predominated at rostral and caudal levels, respectively. Cells consistent with macrophages and shown immunohistochemically to be associated with MV virus were seen in malacic and infiltrative lesions, at the periphery of damaged areas.

Distribution of gonadotropin-releasing hormone neurones in the chick forebrain is independent of lineage relationships among cells of the early nasal placode.

The regulation of reproduction depends upon the successful migration of gonadotropin-releasing hormone (GnRH) neurones from the nasal placode to the ventral forebrain during embryogenesis. Within the central nervous system (CNS), these neurones migrate to stereotyped, highly reproducible locations in septal, preoptic and hypothalamic nuclei. We postulated that lineage relationships (descent from a common precursor) might predict the final location of these neurones. To test this hypothesis, a complex retroviral library was used to label dividing cells in the placode and subsequently to identify them by the presence of the alkaline phosphatase marker. GnRH was detected immunocytochemically and lineage relationships determined by single cell polymerase chain reaction and sequencing of the degenerate oligonucleotide component of the retrovirus. GnRH-positive and GnRH-negative neurones were confined to the side ipsilateral to the injection; many cells derived from the placode that entered the CNS did not contain GnRH. This precise method of identifying and mapping the progeny of single neurones revealed that GnRH cells in any given area were derived from multiple precursors. This developmental pattern may contribute to assuring that all CNS locations critical to the orchestration of reproductive events will be populated by GnRH neurones.

Blepharoclonus in multiple sclerosis.

Keane described 2 patients with gaze-evoked blepharoclonus (BLC), a form of reflex BLC, and multiple sclerosis (MS). A search for common areas of demyelination and focal axonal atrophy (T1 black holes) of the central nervous system (CNS) in 11 patients with MS exhibiting eyelid closure BLC was conducted employing magnetic resonance imaging (MRI). Finding lesions in common CNS locations on these patients can help to elucidate the pathogenesis of this restricted movement disorder. Eleven adult patients with relapsing-remitting, primary or secondary progressive MS were studied. MRI views were completed employing a 1.5-tesla scanner. Contrast Axial T1 imaging was obtained in 9 patients. TL blackholes were not identified. Ten patients had multiple, scattered periventricular (PV) areas of demyelination. Four patients exhibited brainstem lesions of diverse but inconsistent locations including midbrain, cerebellar peduncle, pons and medulla. In 2 of the patients the brainstem lesions were transient but BLC persisted after the lesions regressed. No common areas of CNS demyelination or focal axonal atrophy were identified on these patients with MS and BLC. The pathogenesis and clinical significance of BLC in MS remains to be elucidated.

Primary T-Cell Malignant Lymphoma of the Central Nervous System: Histological, Immunohistochemical and Ultrastructural Study of a Case

Most primary malignant lymphomas (ML) of the central nervous system (CNS) are derived from B-cells, whereas T-malignant lymphomas (T-ML) primarily arising in the CNS are extremely rare. We report on a patient with a primary T-ML of the CNS localised in the posterior fossa. On the basis of histological, ultrastructural and immunohistochemical studies, this tumour was classified as a pleomorphic T-ML, medium and large cell type with peripheral helper/inducer T-cell phenotype (CD 1-, CD 2+, CD 3+, CD 5+, CD 7-, CD 4+, CD 8-, CD 19-, CD 22-, UCHL 1+/CD 45 RO, L 26-/CD 20, LN 1-/CDW75, LN 2-/CD 74, MB 2-). Furthermore, the positivity of the markers CD 25 and HLA-DR on many medium-sized and large lymphoma cells suggests activation of these cells. The nuclear marker of proliferative activity Ki-67 was expressed in some large cells, whereas the natural killer cell-related markers CD 16 and Leu 7/CD 57 did not react with lymphoma cells. This study emphasises the value of extensive immunohistochemical investigations on frozen and paraffin sections in order to identify and characterize the T-cell malignancies, particularly in their rare CNS location.

Intra-axonal virus in demyelinative lesions of experimental herpes simplex type 2 infection

Three-week-old mice which had been infected intracerebrally with herpes simplex virus type 2 (HSV-2) were examined electron-microscopically for the presence of intra-axonal virus in or near optic nerve and spinal cord demyelinative lesions. Acute lesions and their margins frequently contained a very small proportion of abnormal axons, and in a few of these mature virus particles, nucleocapsids, or other incomplete forms were found. A similar range of particle morphology was present in the cytoplasm of infected and degenerating glia. Axons containing similar particles were not identified in fibers in normal white matter surrounding demyelinative lesions. It is proposed that neuronal infection and axonal transport of virus may lead to foci of oligodendroglial infection, destruction and central nervous system (CNS) demyelination near to or remote from the cell bodies of infected neurons. In some instances, the topography of lesions could reflect a tract association. Anatomical features of nervous tissue could favor amplification of demyelination from a relatively minimal neuronal infection, with little evidence of tract degeneration. This hypothesis is consistent with the great predominance of demyelination relative to gray matter disease seen experimentally in non-fatal CNS infections with HSV-2. It would also explain the marked tendency for demyelinative lesions in at least certain CNS locations to be greatly elongated in the long axis of fiber tracts. This mechanism could be of importance in other animal models of virus-induced demyelination, and perhaps also in multiple sclerosis.