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Biomedical subjects

A Schleicher

Publications and source records attributed to A Schleicher.

At least 19 recordsLinked to original sources

Plasticity in the rat hippocampal formation following ibotenic acid lesion of the septal region: a quantitative [14C]deoxyglucose and acetylcholinesterase study.

The local cerebral glucose utilization was measured in the hippocampal formation 3, 21, and 90 days after bilateral lesions of the medial septal nucleus and the nucleus of the diagonal band of Broca by multiple ibotenic acid injections. The CMRglc was determined in hippocampal areas and layers and various limbic and visual regions by quantitative [14C]2-deoxyglucose autoradiography using a computerized image-processing system. Three days after lesion, CMRglc was significantly decreased in 26 of the 38 structures examined. The most pronounced reductions were found in CA2 and CA3, the subiculum, and the parasubiculum. The CMRglc values of the 21- and 90-day postlesion groups did not differ significantly from control data when univariate statistics were used. However, by means of a factor analysis and subsequently a discriminant analysis as a multivariate test for group differences, significant lesion-induced CMRglc changes could be detected between the control group, the 3-day group, and the 90-day group. The 21-day group did not differ significantly from the controls. The data indicate that 90 days after lesion of the medial septum/diagonal band complex (MSDB), a considerable recovery of the mean CMRglc was found in the hippocampal region, although a normal level was not reached. In a parallel series, processing of sections for acetylcholinesterase (AChE) histochemistry revealed a severe destruction of AChE-positive fibers in the hippocampus at 3 days after lesion and a conspicuous recovery in the amount of stainable fibers and their staining intensity at 21 days postlesion. In the 90-day group, the AChE fibers recovered even further but did not reach the values of unlesioned sham-operated controls. The present study indicates that sprouting of surviving cholinergic afferents might be an important morphological substrate for CMRglc recovery in the hippocampus after MSDB lesion.

Acetylcholinesterase

Osteopenia in rats with drug-induced mucopolysaccharidosis.

The immunostimulatory drug tilorone (CAS 27591-97-5) induces generalized lysosomal storage of sulfated glycosaminoglycans, i.e., mucopolysaccharidosis (MPS) in rats. Since inherited MPS of man is often associated with skeletal lesions the present study was performed to investigate whether the tilorone-induced MPS is also accompanied by bone alterations. The answer is yes. Rats (initial age 4 weeks) were orally treated with tilorone (60-80 mg/kg; 6-25 weeks). The proximal tibial metaphysis was examined by radiography and by light and electron microscopy. The tibiae of drug-treated rats remained smaller than those of pair-fed control rats. The primary bone trabecules in drug-treated rats became increasingly shorter, and the cortical bone became thinner. The general organization of the cartilaginous growth plate and the zones of vascular invasion and primary trabecule formation appeared similar as in control rats. Increased numbers of active osteoclasts were found at the free ends of the primary trabecules. Ultrastructurally, MPS-like alterations were observed in all types of bone cells. The osteopenia was partly reversible during recovery periods of more than 6 months after discontinuance of drug treatment. At present, the causal relationship between drug-induced MPS and osteopenia, as well as the mechanisms responsible for osteopenia are unknown. It is suggested that the principal factors are stimulation of osteoclasts and retardation, though not profound distortion, of the events involved in enchondral ossification.

Animals

Developmental gradients of vasoactive intestinal polypeptide (VIP)-containing neurons in the rat visual cortex detected by image analysis.

The postnatal development of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons was followed by computer-assisted image analysis in the rat visual cortex. The laminar distribution of all VIP-IR structures was measured. These structures were subdivided into cell somata, dendritic profiles and axonal boutons and measured separately. VIP-IR neurons were first seen on postnatal day 1, mostly in the upper half of the presumptive visual cortex. A localization of cell bodies similar to that in the adult is reached between days 12 and 16. VIP-IR dendrites have a protracted growth period as compared to perikarya, involving a developmental gradient from an even distribution to a concentration in the upper cortical layers. This is due to the formation of dendritic terminal arbors after the second postnatal week. Scattered VIP-IT axonal boutons appear on day 3 in the midportion of the presumptive visual cortex. Their typical laminar distribution in layers II, IV and lower VI was observed after day 12. Our results suggest that the biochemically detected sharp increase in VIP levels after the second postnatal week is due to the maturation of cell processes as a morphological basis of neuronal connectivity.

Aging

Mapping of glial fibrillary acidic protein-immunoreactivity in the rat forebrain and mesencephalon by computerized image analysis.

Computer-assisted image analysis was used to map the regional distribution of glial fibrillary acidic protein-immunoreactive (GFAP-IR) astrocytes in the rat forebrain and mesencephalon. A complete survey of packing densities of GFAP-IR structures was performed. Computer maps revealed high values in the outer and inner layers of the cortex, some hippocampal and olfactory bulb layers, prepiriform cortex, dorsal part of the caudate-putamen, globus pallidus, lateral septum, reticular thalamic nucleus, lateral habenular nucleus, circumventricular organs, nuclei of the medial hypothalamus, substantia nigra, interpeduncular nucleus, and mamillary body. These correspond to regions of the embryonic pial and ventricular brain surfaces, which undergo developmental alterations including growth and various forms of internalization. From this we conclude that in the adult brain, astrocytes of high GFAP-IR are derivatives of surface-contact glia, whereas those located in areas having developed by the local thickening of the neural tube wall show reduced or no GFAP-IR.

Animals

Functional anatomy of the temporomandibular joint. A morphologic study on human autopsy material.

A study of 72 temporomandibular joints of adults without any gross signs of degenerative changes was made, in order to analyse the stress on individual regions of the joint, and to determine the path of the split line pattern in the articular cartilage. The cancellous architecture and the material distribution in the juxta-articular bone were also investigated. Zones of high-density compact substance in the lateral region of the joint, and the presence of attractive singular points in the split line orientation in this localization, suggest great stress on the lateral part of the temporomandibular joint. This increased stress in the lateral region is confirmed by the fact that arthrotic changes in the temporomandibular joint first almost always appear laterally. Degenerative changes usually originate at the articular disc, affect the articular tubercle after a delay, and finally spread to the condyle. Besides the greater physiological, mechanical stress on the lateral region of the joint, the force acting on every individual temporomandibular joint is influenced by the dental condition. The molars and bicuspids serving as a support zone play a decisive role in this context.

Adult

Postnatal development of forebrain regions in the autoimmune NZB-mouse. A model for degeneration in neuronal systems.

NZB-mice are known to have impaired cognitive functions. The aim of the present study is the analysis of the volume growth of different brain regions in NZB/NBOM-mice, because the functional impairment increases postnatally. The regions analysed include brain structures which are important for learning and memory functions. The comparison between NZB-mice and controls (CFW- and Balb/c-mice) shows that the hippocampal volume in NZB-mice is larger than in controls. However, ectopic neurons are found in the dentate gyrus of NZB-mice, indicating a changed connectivity in this region. The septum and the amygdala show no difference in volume in NZB-mice compared to controls. The adult volume of the entorhinal cortex of the NZB-mice is the smallest of the three strains. The development of this brain region is characterized by an overshooting growth in all strains. The caudate-putamen complex and the globus pallidus of NZB-mice undergo a reduction in volume during the postnatal period. This is not found in the controls. An overshooting growth is seen in the mamillary bodies of the three strains, and in the anterior thalamic nucleus of NZB-mice. However, only the NZB-mice show a prolonged reduction of the volume of the mamillary bodies, which is not finished during the observed time period. Both regions are important relay stations in the Papez-circuit, a neuronal system associated with learning and memory functions. The prolonged postnatal reduction in volume of the mamillary bodies and the anterior thalamic nucleus of NZB-mice may be the structural correlate of the impaired cognition and memory in this strain.

Animals

Local cerebral glucose utilization in the brain of old, learning impaired rats.

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.

Aging

Regional and laminar distributions of alpha 1-adrenoceptors and their subtypes in human and rat hippocampus.

The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.

Animals

Encephalization in hummingbirds (Trochilidae).

The brain mass in 23 hummingbird species was compared to that in galliform birds taking body mass into consideration. Hummingbird brain masses were determined by endocranial volumes, and their body masses were calculated from skeletal measurements. Galliform data were taken from a recent publication. Hummingbirds have brains that are approximately 2.5 times larger than those of galliform birds. Such encephalization may be due to (1) an enlargement of the telencephalon, or (2) an enlargement of functionally well-defined extratelencephalic brain parts. Based on the extremely specialized feeding behavior of the nectarivorous hummingbirds and the neurological demands associated with sucking nectar during hovering, the second hypothesis is better supported, but further studies are needed.

Animals

Neurotransmitter receptors and cortical architecture.

Quantitative receptor autoradiography is a widely used technique for the demonstration of transmitter receptor distributions in anatomically defined brain regions. The present paper reviews some aspects of the relation between receptor distributions and cortical architecture in adult and early postnatal mammalian brains. 1. Changes in the distribution (mean density, laminar pattern) of transmitter receptors occur often at the borders of cyto- and myeloarchitectonically defined cortical areas. This corroborates the functional meaning of the classical cyto- and myeloarchitectonical parcellations. 2. Some, but not all receptor subtypes of one transmitter system and receptors of different transmitter systems show similar laminar patterns (codistribution) and colocalizations at the single cell level. Both aspects are important for a functional interpretation of cortical units (areas, layers, etc.) and neuronal cell types, because the interaction between numerous transmitters and their receptors is the neurochemical substrate of neurotransmission in vivo. Codistributions and colocalizations are prerequisites for such interactions. 3. Overshooting alpha 1-adrenoceptor production, heterochronous development of this receptor in the different layers of a cortical area, and different time tables of cortical histogenesis, increase in transmitter concentrations and local receptor maturation demonstrate that the processes regulating the development of transmitter receptors during postnatal ontogeny cannot be directly deduced from histogenetic events or transmitter maturation in the cortex. 4. Receptors of one transmitter (e.g., alpha 1-adrenoceptors) can be specifically associated with a neuronal projection system (e.g., hippocampal mossy fibers), which is using a different transmitter (e.g., L-glutamate). This points to complex interactions between different transmitter systems in an anatomically defined structure. Functional and architectonical cortical units (e.g., "barrels") show specific receptor distributions, and hitherto unknown modular structures (e.g., periodical concentrations of alpha 1-adrenoceptors in layer V of the rat posteromedial barrel subfield) can be visualized by quantitative receptor autoradiography combined with image analysis.

Aging

Postischemic glucose utilization in rat hippocampal layers.

The influence on hippocampal glucose utilization was determined in male Wistar rats 7 days after a 10-min forebrain ischemia. Ischemia was induced by clamping of the carotid arteries and lowering blood pressure to 40 mm Hg. Despite severe neuronal damage as assessed by histological techniques, local cerebral glucose utilization (LCGU) was significantly increased in the pyramidal and radiatum layer of the CA1 sector, while in layers of the CA2, CA3 and CA4 sector and dentate gyrus. LCGU was reduced compared to non-ischemic controls. The increases in LCGU are suggested to reflect long-lasting hyperexcitation in the selectively vulnerable CA1 sector, implicating a correlation between cellular hypermetabolism and neuronal damage.

Animals

Remote astrocytic response as demonstrated by glial fibrillary acidic protein immunohistochemistry in the visual cortex of dorsal lateral geniculate nucleus lesioned rats.

The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl stained sections in each animal. Electron microscopic observations demonstrated the presence of degenerating axon terminals surrounded by hypertrophic astroglial processes mainly in layers III and IV of the ipsilateral primary visual cortex. The ipsilateral (impaired) and contralateral (control) sides of the primary visual cortex showed light microscopically a clearly differing appearance and distribution of glial fibrillary acidic protein (GFAP) immunoreactivity 7 to 11 days after the unilateral injection of ibotenic acid into the dorsal lateral geniculate nucleus. Whereas the control side of the primary visual cortex showed GFAP staining only in the subpial zone of layer I and close to the white matter, all layers of the impaired cortex showed an intense GFAP immunoreactivity. The increase in immunoreactivity was confined to the primary visual cortex. The extent of and increase in immunoreactivity was corroborated by image analysis. These findings were interpreted as a localized hypertrophy of astroglia caused by the anterograde degeneration of geniculocortical terminals. This hypertrophy is accompanied by an increase in GFAP, which may represent the stabilization of the cytoskeleton of newly formed glial processes involved in the rearrangement of the impaired neuropil.

Afferent Pathways

Local cerebral glucose utilization in the neocortical areas of the rat brain.

The neocortex of the rat brain can be subdivided into regions of different local cerebral glucose utilization (LCGU). However, only a few neocortical areas can be delineated by differences in mean LCGUs between neighbouring areas. These area borders correspond exactly with cytoarchitectonically defined borders found in adjacent Nissl-stained preparations. On the other hand, nearly all of the architectonically defined area borders are also recognizable in the LCGU pictures, if differences in laminar distribution patterns of LCGU are taken into account. Furthermore, interareal differences in mean LCGU mainly reflect changes in layer IV, whereas layers II-III and V-VI show nearly identical LCGU values in all neocortical areas of the rat brain. The primary sensory areas exhibit the highest LCGU in layer IV, while the primary motor cortex shows a high LCGU in layer V. As the cytoarchitectonically defined pattern of the cortex is generally corroborated by the regional and laminar LCGU distribution, anatomical, metabolic and functional aspects of cortical architecture are associated.

Animals

Quantitative analysis of the retrograde reaction of motoneurons with an image analyser.

The neuronal profiles of cell bodies in the facial nerve nucleus of adult rats were measured after partial peripheral nerve transsection. An image analyser was used for automatic recognition and morphometry. Based on classification of the neuronal profiles described in a previous paper, a morphometrical study was performed in order to analyse structural aspects of the retrograde reaction in quantitative terms. Beside the quantification of classical features of retrograde reaction (chromatolysis; nuclear eccentricity; increased basophilia; perikaryal, nuclear and nucleolar swelling), several reactive changes so far not recognized (karyoplasmic basophilia and granulation) were detected. These changes were interpreted as morphological correlates of regeneration in retrogradely reacting cells.

Animals

A new method for quenching correction leads to revisions of data in receptor autoradiography.

Differential quenching of beta-emission affects strongly the analysis of receptor distribution patterns in quantitative receptor autoradiography with tritiated ligands. Different methods for the quenching correction have been described in the past, but some of these are of limited value, if a detailed anatomical parcellation is necessary. Other methods correct exclusively local variations in lipid concentration, which is an important, but only one of several factors causing quenching. A new method for the measurement of quenching (or autoradiographic efficiency) is presented, which permits an anatomically detailed and direct determination of the total quenching without lipid extraction procedures. This method is based on the measurement of autoradiographic efficiency in cryostat sections homogeneously labeled with tritiated formaldehyde by an underlying gelatine section containing this labeled compound. Regional and layer specific measurements of autoradiographic efficiency in cortical and subcortical regions of the human and rat brain are reported. A significant correlation was found between the density of myelin and autoradiographic efficiency but other factors were also shown to influence differential quenching. The use of the here presented correction procedure leads to revisions of the laminar distribution patterns reported for different receptors in human and rat cortical areas. Our results show, that a complete quenching correction is necessary for the mapping of receptor distributions with tritiated ligands.

Animals

Glucose utilization in rat hippocampus after long-term recovery from ischemia.

The influence on hippocampal glucose utilization of a transient 10-min forebrain ischemia was quantified in male Wistar rats after 2 and 3 weeks as well as after 3 months by application of the [14C]2-deoxyglucose technique. Ischemia was induced by occlusion of the carotid arteries and simultaneous lowering of the blood pressure to 40 mm Hg. For identification of the hippocampal architecture, sections were stained for perikarya (cresyl violet) and for acetylcholinesterase. The hippocampal regions clearly showed different responses to the ischemic insult. The necrotic pyramidal cells being almost completely removed, significant increases in glucose utilization occurred in most layers of the CA1 sector at 2 and 3 weeks post ischemia, while widespread reductions prevailed in all other sectors and the dentate gyrus. At 3 months after the ischemic insult, glucose utilization was reduced in all hippocampal structures including the CA1 region. The increases in glucose utilization in the CA1 sector are suggested to indicate long-lasting presynaptic hyperexcitation, while the widespread reductions in glucose utilization demonstrate that neuronal activity is also altered in hippocampal areas that do not show major histological damage.

Animals