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[Neurological effects of American trypanosomyiasis: clinical aspects].

Trypanosoma cruzi, causative agent of Chagas disease, affects not only cardiac and intestinal structures but also neurological structures. A high prevalence of T. cruzi infection occurs in Colombia, prompting the present study. First, a qualitative metaanalysis was undertaken using the PubMed database, the electronic internet engine Altavista, Colombian journals indexed by Colciencias, and three relevant textbooks. The following key words were used: Trypanosoma, Chagas disease, nervous system, spinal cord, central nervous system, peripheral nervous system, neuromuscular junction, autonomic nervous system, muscle, muscle disorders, neuromuscular disease, neuromuscular disorders, synapticopathies and dysautonomia. The documents analyzed numbered 116 and included original papers, reviews, case reports, editorials, brief communications, conferences and book chapters. At minimum, each document included data involving ELISA testing, indirect immunofluorescense, or parasitemia levels in the clinical, serological or histopathological studies. Polymerase chain reaction (PCR) studies were not included because of the recent introduction of PCR as a confirmatory technique for Chagas disease in Colombia. Chagas disease affects the central, the peripheral and the autonomic nervous system in humans, although its effects on the antonomic system is most commonly investigated in Colombia. Neurological lesions must be evaluated carefully, because patients may be misdiagnosed and treated as carriers of 'idiopathic' diseases. Neurological pathologies poses a serious threat in Colombia due to the prevalence of Chagas disease.

Central Nervous System Protozoal Infections↗

Stem-cell plasticity and therapy for injuries of the peripheral nervous system.

Numerous publications have investigated stem-cell biology and the possible therapeutic use of stem cells in a wide range of injuries and diseases. This interest has been fueled by recent reports suggesting that mesenchymal stem cells can show unorthodox plasticity, their being able to transdifferentiate into cells of different lineages, such as neuronal phenotypes. This capability has obvious implications for their potential application in tissue engineering and tissue regeneration. The peripheral nervous system has an inherent capacity for regeneration, but this is limited and not matched by the level of reinnervation of target organs, with a resulting loss of functional recovery. Several approaches have been attempted in order to overcome this deficiency, and transplant of cultured Schwann cells into bioengineered conduits has been shown to improve regeneration. An alternative may be the use of stem-cell technology, whereby cultured and differentiated stem cells can be transplanted to the site of injury in order to promote enhanced regeneration. The present review discusses the use of stem cells applied to the repair of peripheral nerve injury and their role in the regeneration process.

Animals↗

Perineural epithelium: a new concept of its role in the integrity of the peripheral nervous system.

A multilayered, squamous-celled epithelial cell membrane covering the individual nerve fasciculi of the entire peripheral nervous system ( both voluntary and autonomic) including the sensory and motor end organs has been demonstrated in various species of animals, including man. This membrane is the direct continuation of the pia-arachnoid mater from the central nervous system. Functional significance of this membrane, especially as a diffusion barrier and as a protector of the peripheral nervous system, is briefly discussed.

Animals↗

Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system.

Neurotrophins are profound regulators of neuronal survival in the developing peripheral nervous system and are synthesized by peripheral neurons themselves both during development and in maturity. Neuronal neurotrophin expression may be importantly related to survival of mature neurons, both in normal and pathological states. We show here that brain-derived neurotrophic factor (BDNF) gene expression in dorsal root ganglia is strongly stimulated in vivo by another neurotrophin, nerve growth factor (NGF). Furthermore, colocalization studies show that many BDNF-expressing sensory neurons also express trk A, the high-affinity NGF receptor. These results demonstrate a novel regulatory mechanism for neurotrophin gene expression and suggest a paracrine function for neurotrophins in mature animals.

Animals↗

Localization of aquaporin-1 water channel in glial cells of the human peripheral nervous system.

The aquaporins (AQPs) are a family of water channel proteins with at least 13 mammalian members (AQPs 0-12) expressed in diverse fluid transporting tissues. AQP1, AQP4, and AQP9 have been identified in the central nervous system and demonstrated or proposed to play important roles in brain water homeostasis. Aquaporin expression in the peripheral nervous system is poorly studied. Here we report that the AQP1 water channel is specifically localized to glial cells of the peripheral nervous system by immunohistochemistry, RT-PCR, and immunoblotting. Paraffin-embedded biopsies of human pancreas, esophagus, and sciatic nerves were accessed by immunoperoxidase staining using affinity-purified AQP1, AQP4, and AQP9 antibodies. Strong AQP1 expression was identified in pancreatic nerve plexuses and in the submucosal and myenteric nerve plexuses in the esophagus. AQP1 was localized to the same cell population expressing glial fibrillary acidic protein (GFAP), but not to the neurons in the plexuses, indicating glial cell-specific expression. RT-PCR and immunoblot analysis of microdissected pancreatic ganglia confirmed the expression of AQP1 transcript and protein. Pancreatic and sciatic nerve bundles, which contain nonmyelinating and myelinating Schwann cells, respectively, were also selectively labeled by AQP1 antibody. AQP4 and AQP9, which are broadly expressed in astroglial cells in brain and spinal cord, were not localized in glial cells in the peripheral nerve plexuses. These results suggest that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in peripheral neuronal activity by regulating water homeostasis in nerve plexuses and bundles.

Aquaporin 1↗

[A failure of conduction anesthesia in a patient with latent pathology of the peripheral nervous system].

Patients who have been long exposed to ultrasound and high-frequency currents at work are likely to develop diseases of the peripheral nervous system and thus the risk of nerve damage during conduction anesthesia. Profound examination of the peripheral nervous system before surgery is necessary in such patients. In patients with this pathology general anesthesia will be the technique of choice during surgery on the lower extremities.

Adult↗

Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system.

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.

Animals↗

Distribution of neuropeptide Y immunoreactivity in the central and peripheral nervous systems of amphioxus (Branchiostoma lanceolatum Pallas).

Immunocytochemistry techniques were employed to investigate the distribution of neuropeptide Y-like-immunoreactive (NPY-ir) cells and fibers in the central and peripheral nervous systems of adult amphioxus. NPY-ir neurons of the commissural type were abundant in the brain and present but more scarce in the spinal cord. These neurons gave rise to conspicuous NPY-ir tracts that coursed along the entire length of the nerve cord. Some fibers exhibited conspicuous Herring body-like swellings. In the peripheral nervous system, small NPY-ir neurons and a large number of thin, beaded NPY-ir fibers were observed in the atrial region, indicating the involvement of this substance in visceral regulation. A few NPY-ir fibers, possibly afferent to the spinal cord, coursed in the ventral branches of the spinal nerves of this region, whereas no NPY-ir fibers coursed in the preoral or velar nerves or in the dorsal branches of the other spinal nerves. These results indicate that NPY is widely used as a neuroregulator/neurotransmitter in the central and peripheral nervous systems of this primitive chordate. In addition, this study demonstrates the presence of tall, thin NPY-ir cells in the putative adenohypophyseal homologue, the Hatschek's pit organ, which is located in the roof of the preoral cavity (vestibule).

Animals↗

Lineage, cell polarity and inscuteable function in the peripheral nervous system of the Drosophila embryo.

The stereotyped pattern of the Drosophila embryonic peripheral nervous system (PNS) makes it an ideal system to use to identify mutations affecting cell polarity during asymmetric cell division. However, the characterisation of such mutations requires a detailed description of the polarity of the asymmetric divisions in the sensory organ lineages. We describe the pattern of cell divisions generating the vp1-vp4a mono-innervated external sense (es) organs. Each sensory organ precursor (SOP) cell follows a series of four asymmetric cell divisions that generate the four es organs cells (the socket, shaft, sheath cells and the es neurone) together with one multidendritic (md) neurone. This lineage is distinct from any of the previously proposed es lineages. Strikingly, the stereotyped pattern of cell divisions in this lineage is identical to those described for the embryonic chordotonal organ lineage and for the adult thoracic bristle lineage. Our analysis reveals that the vp2-vp4a SOP cells divide with a planar polarity to generate a dorsal pIIa cell and a ventral pIIb cell. The pIIb cell next divides with an apical-basal polarity to generate a basal daughter cell that differentiates as an md neurone. We found that Inscuteable specifically accumulated at the apical pole of the dividing pIIb cell and regulated the polarity of the pIIb division. This study establishes for the first time the function of Inscuteable in the PNS, and provides the basis for studying the mechanisms controlling planar and apical-basal cell polarities in the embryonic sensory organ lineages.

Animals↗

Expression of CD44H in the cells of neural crest origin in peripheral nervous system.

We investigated the expression of the adhesion molecule CD44 in rat peripheral nervous system (PNS) at the protein and mRNA levels. Most migrating neural crest cells strongly expressed CD44, in contrast to the lack of expression in the neural tube. In dorsal root ganglion (DRG) and sciatic nerve, the distribution of CD44, neurofilament (NF) and S100 suggested the localization of CD44 on the membrane of Schwann cell and neurones and in extracellular matrix (ECM). The expression of CD44 was also confirmed on the membrane of cultured neurones and Schwann cells from DRG. mRNA coding for the haematopoietic form of CD44, CD44H, was detected in neural crest cells, DRG neurones and Schwann cells. These results show that CD44 may play some role in migration of neural crest cells and myelination in terms of adhesion between Schwann cells, axons and ECM.

Animals↗

Mytilus inhibitory peptides (MIP) in the central and peripheral nervous system of the pulmonate gastropods, Lymnaea stagnalis and Helix pomatia: distribution and physiological actions.

The distribution and neuroanatomy of Mytilus inhibitory peptides (MIP)-containing neurons in the central nervous system and their innervation pattern in the peripheral nervous system of the pulmonate snail species, Lymnaea stagnalis and Helix pomatia, have been investigated immunocytochemically, by applying an antibody raised to GSPMFVamide. A significant number of immunoreactive neurons occurs in the central nervous system of both species (Lymnaea: ca 600-700, Helix: ca 400-500), but their distribution is different. In Lymnaea, labeled neurons are found in all central ganglia where a number of large and giant neurons, previously identified physiologically, reveal MIP immunoreactivity. In Helix, most of the immunolabeled neurons are small (12-30 microm) and concentrated in the buccal and cerebral ganglia; the parietal ganglia are free of labeled cells. In both species, the ganglionic neuropils, peripheral nerves, connectives, and commissures are richly supplied with immunolabeled fibers. The MIP-immunoreactive innervation pattern in the heart, intestine, buccal mass and radula, and foot is similar in both species, with labeled axonal bundles and terminal-like arborizations (buccal mass, foot) or a network of varicose fibers (heart, intestine). Intrinsic neurons are not present in these tissues. The application of GSPYFVamide inhibits the spontaneous contractions of the esophageal longitudinal musculature in Helix, indicating the bioactivity of the peptide. An outside-out patch-clamp technique has demonstrated that GSPYFVamide opens the K+ channels in central nerve cells of Helix. Injection of GSPYFVamide into the body cavity inhibits the feeding of starved Helix. A wide modulatory role of MIP at central and peripheral levels is suggested in Lymnaea and Helix, including the participation in intercellular signalling processes and remote neurohormonal-like control effects.

Animals↗

Comparison of Schwann cell and sciatic nerve transcriptomes indicates that mouse is a valid model for the human peripheral nervous system.

High-throughput gene expression analyses of murine models of the peripheral nervous system (PNS), and its cellular components, have yielded enormous amounts of expression data of the PNS in various conditions. These data provided clues for future research directions to further decipher this complex organ in relation to acquired and inherited PNS diseases. Various studies addressing the validity of mouse models for human conditions in other tissues and cell types have indicated that in many cases the mouse model only poorly represents the human situation. To determine how well the mouse can serve as model to study the biological processes occurring in the PNS, we compared the gene expression profiles that we generated for mouse and human sciatic nerve and cultured Schwann cells derived thereof. A two-way analysis based on the differentially expressed genes between the sciatic nerve and the cultured Schwann cell, and which takes into account the differential expression between mouse and man, indicates that the human PNS is well represented by that of the mouse in terms of the "biological processes" ontology.

Animals↗

Acetyl-CoA carboxylase and SREBP expression during peripheral nervous system myelination.

The expression of acetyl-CoA carboxylase (ACC) in mouse peripheral nervous system (PNS) was investigated. Both ACC 265 and ACC 280 isoforms were expressed in the sciatic nerve, although ACC 265 was predominant. ACC 265 transcripts originating from promoters P1 and P2 could be detected in the developing nerve, as well as the two splice products, which are characterized by the presence or the absence of a 24-base sequence before the codon serine-1200. The mRNA levels for ACC 265 parallel those of other lipogenic genes whose expression is linked to the myelination process. In addition, ACC 265 mRNA and protein levels in the nerves of the trembler mutant, which is a mouse model of PNS dysmyelination, represented around 30% of the normal values. The expression of the sterol regulatory element-binding proteins (SREBPs) was also studied. SREBP 1 mRNAs were expressed at a constant level during nerve development, and their quantities were normal in trembler. On the contrary, SREBP 2 mRNA quantities varied during the myelination period similarly to the lipogenic gene mRNAs, and the levels measured in trembler represented only 10% of the normal values. Taken together, these results suggest that the coordinate expression of several lipogenic genes, which occurs during PNS myelination, could possibly be regulated by SREBP 2.

Acetyl-CoA Carboxylase↗

Effects of drugs which depress the peripheral nervous system on the reticular activating system of the cat.

Some drugs with depressant properties on the peripheral nervous system have been examined for depressant effects on the reticular activating system of the cat. Large doses of nicotine, or of the anti-nicotinic agents dihydro-beta-erythroidine and mecamylamine, failed to depress the reticular activating system; non-quaternary drugs with anti-muscarinic properties, such as atropine and hyoscine, depressed it readily. Hyoscine was the most potent depressant tested and its effects could be antagonized by physostigmine. In contradistinction, depression of the reticular activating system with pentobarbitone was not antagonized by physostigmine. Lignocaine was a weak depressant of the reticular activating system, and the possibility that this might be due to a central anti-muscarinic action is discussed. Adrenergic blocking drugs, such as dihydroergotamine, phenoxybenzamine or choline 2:6-xylyl ether, did not appear to depress the reticular activating system: the significance of this is discussed. It was concluded that the hypothetical cholinergic transmitter, acting somewhere within the reticular activating system, displayed actions analogous to the muscarinic, and not to the nicotinic, actions of acetylcholine.

Acetylcholine↗

Clinical and electrophysiological study of the peripheral nervous system in the elderly.

The effect of age on the peripheral nervous system was investigated by clinical examination and neurophysiological studies in 59 subjects aged 60-103 years and 23 young subjects. A full laboratory screen for factors which, though clinically silent, may constitute risk factors (RFs) for peripheral neuropathy was also performed in the elderly subjects. Our findings show that the presence of RFs affects exceptionally the electrophysiological parameters in a statistically significant way. The age-dependent changes in nerve conduction parameters were well predicted by non-linear models. The simultaneous electromyographical study demonstrates the re-innervation capacity of the motor system.

Action Potentials↗