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Seven beef cattle from a herd accidentally exposed to acrylamide and N-methylolacrylamide while grazing were observed for eight months. They showed clinical signs of impaired nerve function, mainly in the hindlegs, with varying degrees of weakness and ataxia. The animals were irritable, nervous and hypersensitive to touch. Both pupils of the most badly affected animal were dilated and it had poor pupillary light responses; it also showed signs of axonal neuropathy. Selected haematological and clinical chemistry variables were normal. The severity of the neurological signs was correlated with the concentrations of haemoglobin adducts of acrylamides. The animals recovered substantially after their exposure. The gestations of four of the animals which were in calf proceeded normally.
Vet Rec 2002 Dec 14
PMID:Acrylamide and N-methylolacrylamide poisoning in a herd of Charolais crossbreed cattle. 1251 Jun 66

Olfactory ensheathing cells (OECs), a unique type of macroglia required for normal olfactory axonal regeneration throughout the lifetime of an individual, have been shown to have regeneration-enhancing properties when used to treat various neuronal injuries. Availability of OECs is a hurdle facing future clinical use of the cells for spinal cord injury (SCI) therapy. The number of OECs that can realistically be harvested from each animal is limited, and ensuring a pure cell population is difficult. We have begun to characterize a nonsyngeneic strain of OECs, i.e., from a homogenous OEC clonal cell line (nOECs). The purpose of this study was to determine whether nOECs have the same properties and provide the same functional recovery after SCI, as primary cultures of OECs. The results indicate that nOECs survive in vivo, produce growth-promoting proteins, and possess regeneration-promoting capabilities. Spinal cord injured rats that were treated with nOECs performed significantly better on functional tests than injured control animals beginning at 5 weeks after operation. In summary, evidence of nOEC regeneration-promoting capabilities suggests that this cell line can be used as potential therapy in SCI research.
Anat Rec B New Anat 2003 Mar
PMID:Use of a cell line to investigate olfactory ensheathing cell-enhanced axonal regeneration. 1261 87

A therapy to treat injuries to the central nervous system (CNS) is, to date, a major clinical challenge. The devastating functional consequences they cause in human patients have encouraged many scientists to search, in animal models, for a repair strategy that could, in the future, be applied to humans. However, although several experimental approaches have obtained some degree of success, very few have been translated into clinical trials. Traumatic and demyelinating lesions of the spinal cord have attracted several groups with the same aim: to find a way to promote axonal regeneration, remyelination, and functional recovery, by using a simple, safe, effective, and viable procedure. During the past decade, olfactory ensheathing glia (OEG) transplantation has emerged as a very promising experimental therapy to promote repair of spinal cords, after different types of injuries. Transplants of these cells promoted axonal regeneration and functional recovery after partial and complete spinal cord lesions. Moreover, olfactory ensheathing glia were able to form myelin sheaths around demyelinated axons. In this article, we review these recent advances and discuss to what extent olfactory ensheathing glia transplantation might have a future as a therapy for different spinal cord affections in humans.
Anat Rec B New Anat 2003 Mar
PMID:Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system. 1261 89

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development.
Anat Rec A Discov Mol Cell Evol Biol 2006 Feb
PMID:Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain. 1641 Dec 47

Tactile information from the rodent mystacial vibrissae is relayed through the ascending trigeminal somatosensory system. At each level of this pathway, the whiskers are represented by a unique pattern of dense cell aggregates, which in layer IV of cortex are known as "barrels." Afferent inputs from the dorsal thalamus have been demonstrated repeatedly to correspond rather precisely with this modular organization. However, axonal innervation patterns from other brain regions such as the noradrenergic locus coeruleus are less clear. A previous report has suggested that norepinephrine-containing fibers are concentrated in the center/hollow of the barrel, while other studies have emphasized a more random distribution of monoaminergic projections. To address this issue more directly, individual tissue sections were histochemically processed for cytochrome oxidase in combination with dopamine-beta-hydroxylase, the synthesizing enzyme for norepinephrine, or the neuropeptide galanin. These two neuroactive agents were of particular interest because they colocalize in a majority of locus coeruleus neurons and terminals. Our data indicate that discrete concentrations or local arrays of dopamine-beta-hydroxylase- or galanin-immunoreactive fibers are not apparent within the cores of individual barrels. As such, the data suggest that cortical inputs from the locus coeruleus are not patterned according to cytoarchitectural landmarks or the neurochemical identity of coeruleocortical efferents. While transmitter-specific actions of norepinephrine and/or galanin may not be derived from the laminar/spatial connections of locus coeruleus axons, the possibility remains that the release of these substances may mediate distinctive events through the localization of different receptor subclasses, or the contact of their terminals onto cells with certain morphological characteristics or ultrastructural components.
Anat Rec A Discov Mol Cell Evol Biol 2006 Feb
PMID:Characterization of neurochemically specific projections from the locus coeruleus with respect to somatosensory-related barrels. 1641 3

The innervation of the cochlear sensory epithelium is intricately organized, allowing the tonotopy established by the auditory hair cells to be maintained along the ascending auditory pathways. These auditory projections are patterned by several gene families that regulate neurite attraction and repulsion, known as axon guidance cues. In this review, the roles of various axon guidance molecules, including fibroblast growth factor, ephs, semaphorins, netrins and slits, are examined in light of their known contribution to auditory development. Additionally, morphogens are discussed in the context of their recently described influence on axonal pathfinding in other sensory systems. The elucidation of these various mechanisms may guide the development of therapies aimed at maximizing the connectivity of auditory neurons in the context of congenital or acquired sensorineural hearing loss, especially as pertains to cochlear implants. Further afield, improved understanding of the molecular processes which regulate innervation of the organ of Corti during normal development may prove useful in connecting regenerated hair cells to the central nervous system.
Anat Rec A Discov Mol Cell Evol Biol 2006 Apr
PMID:Axon guidance cues in auditory development. 1655 May 48

Multipolar cells in the ventral cochlear nucleus (VCN) are a structurally and functionally diverse group of projection neurons. Understanding their role in the ascending pathway involves partitioning multipolar cells into distinct populations and determining where in the brain each sends its coded messages. In this study, we used retrograde labeling techniques in rats to identify multipolar neurons that project their axons to the ipsilateral dorsal cochlear nucleus (DCN), the contralateral CN, or both structures. Three rats received injections of biotinylated dextran amine in the ipsilateral DCN and diamidino yellow in the contralateral CN. Several radiate multipolar neurons (defined by their axonal projections to the ipsilateral DCN and their dendrites that traverse VCN isofrequency sheets) were double-labeled but over 70% were not. This result suggests two distinct populations: (1) radiate-commissural (RC) multipolar cells that project to the ipsilateral DCN and the contralateral CN, and (2) radiate multipolar cells that project exclusively (in this context) to the ipsilateral DCN. In a different group of animals, we retrogradely labeled multipolar neurons that project their axons to the contralateral CN and measured the size of their cell bodies. The mean size of this population (266 +/- 156 microm2) was significantly smaller than those of RC-multipolar cells (418 +/- 140 microm2). We conclude that the CN commissural pathway is composed of at least two components: (1) RC multipolar cells and (2) commissural multipolar cells that are small- and medium-sized neurons that project exclusively (in this context) to the contralateral CN. These results identify separate structural groups of multipolar cells that may correspond to physiological unit types described in the literature. They also provide protocols for isolating and studying different populations of multipolar cells to determine the neural mechanisms that govern their responses to sound.
Anat Rec A Discov Mol Cell Evol Biol 2006 Apr
PMID:Structural and functional classes of multipolar cells in the ventral cochlear nucleus. 1655 May 50

The relationship between structure and function is clearly illustrated by emerging evidence demonstrating the role of the neuronal cytoskeleton in physiological processes. For example, alterations in axonal caliber, a feature of the cytoskeleton, have been shown to affect reflex arc latencies and are prominent features of several neuropathological disorders. Even in the nonpathologic situation, however, axonal diameter may be a crucial element for the normal function of specialized auditory neurons. To investigate this relationship, we used serial analysis of gene expression and microarray analyses to characterize the expression of cytoskeletal genes in the central auditory system. These data, confirmed by real-time RT-PCR, identified differential expression of intermediate neurofilament transcripts (i.e., Nefh, Nef3, and Nfl) among the subdivisions of the cochlear nucleus. In situ hybridization was used to identify specific classes of neurons within the cochlear nucleus expressing these neurofilament genes. Robust neurofilament expression was seen in bushy cells and cochlear nerve root neurons, suggesting an association between cytoskeletal structure and rapid conduction velocities. Gene expression data were also identified for other classes of cytoskeletal and structural genes important in neuronal function. These results may help to explain some causes of hearing loss in hereditary neuropathies and provide an anatomic basis for understanding normal neuronal function in the central auditory system.
Anat Rec A Discov Mol Cell Evol Biol 2006 Apr
PMID:Differential expression of cytoskeletal genes in the cochlear nucleus. 1655 May 90

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection.
Anat Rec A Discov Mol Cell Evol Biol 2006 Dec
PMID:Projections of somatosensory cortex and frontal eye fields onto incertotectal neurons in the cat. 1708 21

The noradrenergic (NA) innervation in the trigeminal motor nucleus (Vmot) of postnatal and adult rats was examined by light and electron microscopic immunocytochemistry using antibodies against dopamine-beta-hydroxylase or tyrosine hydroxylase. NA fibers were identified in the Vmot as early as the day of birth (postnatal day 0; P0). A continuous increase in the density of labeled fibers was observed during development up to P20, with a slight decrease at P30 and in the adult. Electron microscopic analysis of serial ultrathin sections revealed that, at P5, nearly half (46%) of the examined NA terminals made synaptic contact with other neuronal elements with membrane specializations. The percentage of examined NA varicosities engaged in synaptic contacts increased at P15 (74%), then decreased in the adult (64%). At all developmental ages, the majority of contacts made by these boutons were symmetrical, the postsynaptic elements being mainly dendrites and occasionally somata. Interestingly, some of the NA terminals made axo-axon contacts with other unidentified boutons. These results show that, although the density of NA fibers increases during postnatal development, functional NA boutons are present in the Vmot at early postnatal ages. Some of these fibers might exert their effects via nonsynaptic release of noradrenaline, the so-called volume transmission, but, in the main, they form conventional synaptic contacts with dendrites, somata, and other axonal terminals in the Vmot. These results are consistent with previous electrophysiological studies that propose an important role for the NA system in modulating mastication.
Anat Rec (Hoboken) 2007 Jan
PMID:Postnatal development of noradrenergic terminals in the rat trigeminal motor nucleus: A light and electron microscopic immunocytochemical analysis. 1744 Dec 2


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