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Biomedical subjects

C D Ross

Publications and source records attributed to C D Ross.

At least 19 recordsLinked to original sources

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine.

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Animals↗

Spinal taurine levels are increased 7 and 30 days following methylprednisolone treatment of spinal cord injury in rats.

The amino acid taurine serves many functions in the nervous system serving as inhibitory neurotransmitter/neuromodulator, neurotrophin, antioxidant, and osmolyte. Taurine levels are increased following brain injury and glucocorticoid administration. Thus, the purpose of this study was to examine spinal taurine concentrations following spinal cord injury (SCI) and methylprednisolone (MP) treatment of SCI. A total of 44 adult male Sprague-Dawley rats were divided into control and lesion groups. Control rats received a T6 vertebral laminectomy while lesioned rats received a laminectomy followed by complete spinal transection. Half of the animals in each group received MP intravenously following sham-operation or SCI. Rats survived for 7 or 30 days and concentrations of taurine in spinal gray and white matter, in spinal segments both near and distant from the injury epicenter, were resolved by HPLC analysis. Taurine levels were increased 7 and 30 days following transection in spinal segments immediately adjacent to the lesion and were further elevated by MP treatment. No increases were seen in far rostral/caudal segments, and MP treatment alone had no effect on spinal taurine levels. These findings demonstrate that spinal injury results in increased taurine concentrations in spinal segments undergoing the greatest degree of cellular reactivity and tissue reorganization and that MP therapy potentiates these increases. These findings are significant in that they further characterize the effects of acute MP therapy in spinal tissue. Since taurine is thought to be involved in neuroprotection and/or regeneration following injury, the potentiation of taurine levels by MP treatment may relate to its therapeutic properties.

Animals↗

Glutamine synthetase activities in spinal white and gray matter 7 days following spinal cord injury in rats.

The glial enzyme glutamine synthetase (GS) is critical for central nervous system catabolism of glutamate and glutamine production. Upregulation of GS is a hallmark of reactive astrocytosis, although such induction following spinal cord injury (SCI) has not been reported. This study's purpose was to determine if GS activity is increased following SCI. Experimental rats received a complete spinal transection at the T5 segment and control rats received a laminectomy only. GS activities were determined using an enzymatic microassay. Glutamine levels were resolved in semi-adjacent sections. At 7 days following SCI, GS activity increased an average of 170-190% in white matter and 15-25% in gray matter immediately adjacent to the transection, and 70-90% in white matter and 40-45% in gray matter from cervical and lumbar enlargements. Correlative increases in glutamine were observed also. These findings further characterize the astrocytic response to SCI, which may contribute to altered glutamine metabolism in injured spinal tissue.

Animals↗

Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma.

Squamous cell carcinomas were evaluated with respect to tumor differentiation (through use of hematoxylin and eosin stain), microvessel density (through use of CD-34 immunocytochemical stain), and magnitudes of malate dehydrogenase (MDH), hexokinase, and lactate dehydrogenase (LDH) enzyme activities. Direct correlations were found between tumor grade, MDH activity, and microvessel density. Direct correlations were also found between hexokinase activity and MDH activity and microvessel density. Inverse correlations were found between LDH activity and both tumor grade and MDH activity. These results suggest that the high rate of glucose utilization (indicated by hexokinase activity) found in more poorly differentiated tumors has a higher component of aerobic oxidative metabolism (indicated by MDH activity) and a relatively lower contribution from anaerobic metabolism (indicated by LDH activity) than do the rates found in more differentiated tumors. It is also suggested that as the glycolytic rate increases, more pyruvate goes into the Krebs cycle than into lactate. The availability of glucose-derived pyruvate for oxidative metabolism would mean less of a dependency on glutamine as a carbon source in squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Quantitative biochemical analysis of samples from squamous cell carcinoma.

Samples of tumor, tumor stroma, and mixed tumor and stroma were microdissected from three squamous cell carcinomas, as well as from adjacent nontumor tissue and assayed for malate dehydrogenase or lactate dehydrogenase activity as indicators of the relative contribution of aerobic and anaerobic processes, respectively, to energy metabolism. Malate and lactate dehydrogenase activities were greater in tumor tissue than in tumor stroma in all three tumors. However, the magnitudes of malate and lactate dehydrogenase activities were different among the tumors, suggesting that tumors vary in the degree to which aerobic and anaerobic reactions contribute to energy production. These results indicate that a quantitative assessment of enzymes involved in energy production may be a useful probe in the understanding of tumor metabolism.

Carcinoma, Squamous Cell↗

Changes in brainstem calcitonin gene-related peptide after VIIth and VIIIth cranial nerve lesions in guinea pig.

The present study investigated the effect of seventh and eight cranial nerve lesions on the prominence of calcitonin gene-related peptide in the hypoglossal (XII), facial (VII), abducens (VI), and oculomotor (III) cranial nerve nuclei. Guinea pigs were anesthetized and subjected to unilateral cochlear removal, vestibular end organ ablation, and seventh nerve transection. After a survival period ranging from 4 h to 5 days, each animal was anesthetized and perfused intracardially. Frozen sections were collected through the brainstem and stained immunohistochemically for calcitonin gene-related peptide using a polyclonal antibody with the Vectastain ABC kit and protocol. Positive cells were counted in each nucleus bilaterally and analyzed for side to side differences. Nuclei XII and III showed no significant difference in the numbers of cells staining positively for calcitonin gene-related peptide between the ipsilateral and the contralateral sides to the lesion. However, nuclei VII and VI showed elevated numbers ipsilateral to the lesion on some days, but not all. For VII, there was no significant difference before 24 h, but there were significant differences 1-5 days after the lesion. Similarly, in VI, there was no difference before 24 h, but differences were significant beginning with day 1 and continuing through day 3, and finally disappearing by day 4. Changes in the numbers of CGRP positive cells in VII measurable 24 h after the lesion and continuing for at least 5 days afterward indicate a central nervous system retrograde response to peripheral motor nerve injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Abducens Nerve↗

Amino acid concentrations and selected enzyme activities in rat auditory, olfactory, and visual systems.

Homogenates of specific brain regions of three sensory systems (auditory, olfactory, and visual) were prepared from pigmented Long-Evans Hooded rats and assayed for amino acid concentrations and activities of glutaminase, aspartate aminotransferase (total, cytosolic, and by difference, mitochondrial), malate dehydrogenase, lactate dehydrogenase, and choline acetyltransferase. Comparing the quantitative distributions among regions revealed significant correlations between AAT and aspartate, between glutaminase and glutamate, between glutamate and glutamine, and between AAT plus glutaminase, or glutaminase alone, and the sum of aspartate, glutamate, and GABA, suggesting a metabolic pathway involving the synthesis of a glutamate pool as precursor to aspartate and GABA. Of the inhibitory transmitter amino acids, GABA concentrations routinely exceeded those of glycine, but glycine concentrations were relatively high in brainstem auditory structures.

Amino Acids↗

Aspartate aminotransferase and glutaminase activities in rat olfactory bulb and cochlear nucleus; comparisons with retina and with concentrations of substrate and product amino acids.

The quantitative distributions of aspartate aminotransferase and glutaminase were mapped in subregions of olfactory bulb and cochlear nucleus of rat, and were compared with similar data for retina and with the distributions of their substrate and product amino acids aspartate, glutamate, and glutamine. The distributions of both enzymes paralleled that of aspartate in the olfactory bulb and that of glutamate in the cochlear nucleus. In retina (excluding inner segments), there were similarities between aspartate aminotransferase and both glutamate and aspartate distributions. The distribution of gamma-aminobutyrate (GABA) was similar to those of both enzymes in olfactory bulb, to aspartate aminotransferase in cochlear nucleus, and to glutaminase in retina (excluding inner segments). The results are consistent with significant involvement of aspartate aminotransferase, especially the cytosolic isoenzyme, and glutaminase in accumulation of the neurotransmitter amino acids glutamate, aspartate, and GABA, although with preferential accumulation of different amino acids in different brain regions.

Amino Acids↗

Distributions of choline acetyltransferase and acetylcholinesterase activities in the retinal layers of the red-tailed hawk and road runner.

The activities of choline acetyltransferase and acetylcholinesterase were assayed in submicrogram samples from layers of red-tailed hawk and road runner retina. Both enzyme activities were concentrated in and near the inner plexiform layer. Within the inner plexiform layers of both species, activities of each enzyme were concentrated in two bands, one in each half of this layer. Little choline acetyltransferase activity was found superficial to the middle third of the inner nuclear layer. The distributions of acetylcholinesterase activities corresponded well to those of choline acetyltransferase, except in the outer plexiform layer and the outer margin of the inner nuclear layer of the hawk. These distributions of enzyme activities indicate that populations of amacrine cells in the retinae of these species are cholinergic. In addition to these same cells and presumably cholinoceptive amacrine and ganglion cells, acetylcholinesterase activity in the hawk was associated with a population of horizontal cells that may be unrelated to synaptic cholinergic neurotransmission. Choline acetyltransferase activities associated with amacrine somata and processes were about four times greater in the hawk than in the road runner, suggesting important differences in the density and function of cholinergic elements between species. Possible synaptic relationships in the inner plexiform layer consistent with the interspecies differences in enzyme activities are considered.

Acetylcholinesterase↗

Distributions of choline acetyltransferase and acetylcholinesterase activities in the retinal layers of pigeon red and yellow fields.

The activities of choline acetyltransferase and acetylcholinesterase were assayed in submicrogram samples from layers of pigeon retina. Red and yellow fields were sampled separately to investigate quantitatively the relationship between these enzymes of acetylcholine metabolism and the gradient of inner plexiform layer complexity, increasing from the yellow field to the red. Choline acetyltransferase and acetylcholinesterase activities were concentrated in and near the inner plexiform layer, within which two peaks of activity for each enzyme were obtained. The distributions of enzyme activities indicate that populations of amacrine cells in the pigeon retina are cholinergic. The quantitative similarities between the enzyme activities in red and yellow fields suggest that the cholinergic system may not be specifically involved in the increase in inner plexiform layer complexity across the pigeon retina.

Acetylcholinesterase↗

Enzymes of transmitter and energy metabolism in rat middle ear and extraocular muscles.

To further investigate the peculiar characteristics of the middle ear and extraocular muscles, compared to the extensively studied skeletal muscles of the limbs, activities of enzymes of transmitter and energy metabolism were measured in homogenates of these muscles from albino and pigmented rats. These activities were compared to those for a masticatory muscle and for three hindlimb muscles chosen for their preponderance of either slow oxidative, fast glycolytic, or fast oxidative glycolytic fibers. Activities of the neuromuscular transmitter enzymes choline acetyltransferase and acetylcholinesterase were relatively very high in the extraocular and middle ear muscles. The activity of malate dehydrogenase, an enzyme of oxidative energy metabolism, was as high in the extraocular, masticatory and stapedius muscles as in the oxidative hindlimb muscles, but was lower in tensor tympani. The activity of lactate dehydrogenase, an enzyme of glycolytic energy metabolism, was remarkably low in both middle ear muscles. The results are consistent with high innervation density in the extraocular and middle ear muscles, and highly oxidative metabolism in the extraocular and stapedius muscles. Metabolic differences between the stapedius and tensor tympani suggest a relatively more active role for the former in the function of the rat middle ear.

Animals↗

Contribution of centrifugal innervation to choline acetyltransferase activity in the cat cochlear nucleus.

Using a quantitative microchemical mapping approach combined with surgical cuts of fiber tracts, the contributions of centrifugal pathways to choline acetyltransferase activity were mapped three-dimensionally in the cat cochlear nucleus. Large reductions of choline acetyltransferase activity, averaging 70%, were measured in almost all parts of the lesion-side nucleus following transection of virtually all its centrifugal connections. More superficial cuts, penetrating just through the olivocochlear bundle, also led to significant reductions of enzyme activity, especially most rostrally in the anteroventral cochlear nucleus and superficial granular region, where the reductions were similar to those following the complete cuts. Lesions encroaching upon the superior olivary complex gave bilateral effects. Transverse cuts between rostral and caudal parts of the cochlear nucleus gave some small effects. The results suggest that, as in rats, most choline acetyltransferase activity in the cat cochlear nucleus is associated with its centrifugal innervation. However, unlike the situation in rats, the enzyme activity in cats is related more to olivocochlear branches than to ventral fibers in the trapezoid body region. Also, the choline acetyltransferase activity related to olivocochlear collateral innervation is much less uniformly distributed within the cochlear nucleus in cats than in rats.

Animals↗

Quantitative distributions of aspartate aminotransferase and glutaminase activities in the guinea pig cochlea.

Distributions of aspartate aminotransferase and glutaminase activities in the guinea pig cochlea have been examined with use of quantitative microchemical techniques to evaluate their roles in cochlear energy metabolism and neurotransmission. Other enzyme activities analyzed were those of choline acetyltransferase and malate dehydrogenase. It is concluded that aspartate aminotransferase activity appears to be especially concerned with cochlear energy metabolism, while glutaminase activity may function in transmitter metabolism in the guinea pig cochlea. Neither enzyme shows a clear association with the olivocochlear bundle.

Animals↗

Enzymes of transmitter and energy metabolism in cat middle ear muscles.

Activities of the enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), which metabolize the neuromuscular transmitter acetylcholine, and malate and lactate dehydrogenase (MDH and LDH), enzymes of oxidative and glycolytic energy metabolism, respectively, were measured in the middle ear muscles of the cat. For comparison, the same enzyme activities were measured in extraocular muscle tissue and in three hindlimb muscles rich in either slow oxidative (soleus), fast glycolytic (white part of vastus lateralis), or fast oxidative glycolytic (plantaris) muscle fibers. ChAT and AChE activities were much higher in middle ear muscles than in hindlimb muscles, consistent with a denser neuromuscular innervation, as in extraocular muscles. By contrast, MDH and LDH activities were remarkably low in the middle ear muscles, lower than in any of the hindlimb muscles or the extraocular muscles. Denervation of the stapedius muscle by peripheral transection of the facial nerve resulted in decreases in all four enzyme activities without associated changes in the tensor tympani. Surgical ablation of the peripheral facial nerve supply to the stapedius muscle appears to be a feasible option for producing its denervation. The results suggest some rather specialized chemical characteristics for the middle ear muscles.

Acetylcholinesterase↗

Quantitative distribution of six amino acids in rat retinal layers.

Concentrations of glutamate, aspartate, glutamine, glycine, GABA, and taurine were determined in samples microdissected from rat retinal layers and assayed by HPLC. Glutamate and glutamine were relatively high in the inner nuclear (INL) and ganglion cell (GCL) layers; aspartate was relatively high in the outer nuclear layer (ONL), outer plexiform layer, and INL. Distributions of glutamate and aspartate did not correlate well with those of enzymes involved in their metabolism. Glycine and GABA were highest in the inner plexiform layer, with increasing concentrations through the INL, and were relatively high in the GCL. Taurine was highest in the ONL.

Amino Acids↗

Effect of septal ablation on choline acetyltransferase in the paraventricular nucleus.

To determine whether there is a cholinergic projection from the lateral septum to the paraventricular nucleus of the hypothalamus (PVH), a quantitative histochemical analysis of the effects of unilateral ablation (0.5 microliter of a 10 micrograms/ml solution of ibotenic acid) of the lateral septum (LSV) on the choline acetyltransferase (ChAT) activity of the PVH and surrounding perinuclear area was undertaken. Comparisons of the ChAT activity of the PVH region ipsilateral to the LSV lesion (lesioned side) with that of the PVH contralateral (nonlesioned side) to the ablated LSV showed a 20% reduction (p less than 0.05) of ChAT activity in 2 areas of the PVH on the lesioned side. When ChAT activity of LSV-ablated and intact control rats was compared, a 20% difference in activity (p less than 0.05) was noted in four areas on the nonlesioned side and a 35% difference (p less than 0.05) of ChAT activity was noted in five regions of the PVH on the lesioned side of LSV-ablated animals. Taken together these data suggest that the pathway from the LSV to the PVH contains a small, bilateral cholinergic component. However, the data also indicate that this is not the only cholinergic projection to the PVH.

Animals↗

Quantitative inter-strain comparison of the distribution of choline acetyltransferase activity in the rat cochlear nucleus.

The distribution of choline acetyltransferase activity in the cochlear nucleus of Sprague-Dawley albino rats was quantitatively compared to those in two strains of pigmented rats, Long Evans hooded and Brown Norway, using microdissection and radiometric assay techniques. Although activities tended to be, on the whole, higher in the albino rats, the differences were fairly minor. The relative distributions of choline acetyltransferase activity were generally similar among the 3 rat strains, not only among regions, but also within regions. Stain for acetylcholinesterase activity in the cochlear nucleus also had a similar appearance among the 3 rat strains. These chemical results are consistent with previous anatomical and physiological studies suggesting that auditory differences between albino and pigmented animals may not be as great in the cochlear nucleus as in the superior olivary complex.

Animals↗