The challenge of involvement.
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Biomedical subjects
Publications and source records attributed to D M Armstrong.
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1. Field potentials and single unit discharges were recorded in the dorsal accessory olive of the cat following stimulation of nerves of the contralateral hind limb.2. The largest field potentials were evoked when nerves were stimulated with brief trains at 200-300/sec. Responses were sometimes evoked from quadriceps nerve by volleys restricted to low threshold group I afferents, but responses were not usually evoked from other muscle nerves unless both group I and II afferents were excited.3. The spatial distributions of the field potentials evoked from different nerves were very similar and individual units were made to discharge by stimulation of each of a wide range of nerves including muscle, skin and joint nerves. Single units were also made to discharge by stimulation of both the ipsilateral and the contralateral quadriceps nerve.4. The latency of the field potentials evoked by stimulation of quadriceps nerve ranged from 14 to 23 msec in different preparations. The latency of responses evoked from various branches of the sciatic nerve was consistently longer and was usually between 20 and 30 msec.5. The activity was conveyed by a tract which, at the upper lumbar level of the spinal cord, lay in the ventral quadrant ipsilateral to the olive. In the upper cervical region the tract lay close to the ventral surface of the cord. Values between 24 and 30 m/sec were found for the conduction velocity of the tract.6. An excitatory response in the dorsal accessory olive was followed by a period of about 100 msec during which the amplitude of a second response was reduced.
1. Surface potentials, similar to those found by earlier workers, have been recorded from the vermis of the anterior lobe of the cerebellum following stimulation of muscular, cutaneous and articular nerves of the ipsilateral hind limb. The most conspicuous component of the response consisted of a positive potential succeeded by a smaller negative potential.2. Micro-electrode recordings showed that this component coincided both with climbing fibre responses in individual Purkinje cells, and with extracellular field potentials within the cerebellar cortex which closely resembled those found by Eccles, Llinás & Sasaki (1966) following electrical stimulation of the inferior olive.3. Stimulation of the cerebellar surface, in the region where the responses to limb nerve stimulation were largest, led to antidromic invasion of neurones of the contralateral inferior olive. The antidromic action potentials were sometimes followed by up to three orthodromic spikes. Histological techniques were used to show that these neurones were located in the caudal parts of the dorsal and medial accessory olives.4. Stimulation of nerves of the hind limb evoked discharges of the same neurones of the dorsal accessory olive which were antidromically invaded from the vermis of the anterior lobe. The nerves used (quadriceps, gastrocnemius-soleus, sural and the posterior nerve to the knee joint) were shown to excite heavily overlapping populations of neurones.5. Those neurones of the medial accessory olive, which were identified antidromically from the anterior lobe vermis, were not discharged by stimulation of hind limb nerves.6. Simultaneous recording from the surface of the anterior lobe and from the dorsal accessory olive showed that the onset of olive cell discharges occurred about 5 msec before the onset of the positive potential at the cerebellar surface.
Immunocytochemical techniques were employed in order to examine the distribution and relative intensity of immunolabeling of the alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptor subunits GluR1 and GluR2/3 within the hippocampal formation of patients with Alzheimer disease (AD). Within sectors of the hippocampus that are particularly vulnerable to AD pathology (i.e., CA1, subiculum), we observed a variable loss of GluR1 and GluR2/3 immunolabeling correlating with the extent of cell loss and neurofibrillary pathology. In contrast, in less vulnerable sectors of the hippocampus (i.e., CA2/3, dentate gyrus), the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular and polymorphic layers of the dentate gyrus. Importantly, these latter regions correspond to termination zones of glutamatergic perforant pathway axons and mossy fiber collaterals, respectively. The increase in immunolabeling within these projection fields is hypothesized to occur in response to the deafferentation of selected glutamatergic pathways, and suggests a critical role for AMPA receptor subunits in hippocampal plasticity.
In order to determine whether cortical fibrous astrocytes increase with age, we studied 25 patients ranging in age from 24 to 100 years with no clinical or pathological evidence of dementia or other cerebral disorder. Paraffin sections of mid-frontal cortex were obtained and stained with the avidin-biotin immunolabeling procedure for glial intermediate filament protein. The resulting immunolabeled fibrous astrocytes were then counted in the molecular and cellular (cortical laminae 2-6) layers. Populations of fibrous astrocytes in both layers varied widely among individuals, and in the molecular layer their numbers were not significantly correlated with advancing age. In the cellular layer, however, despite widely ranging cell counts among individuals within the same decades of life, there was a significant linear increase with age. Our data suggest that the increase occurs or accelerates significantly after age 70, but the case numbers preclude reaching such a conclusion with statistical confidence. However, when the patients are divided into those less than 70 and those older, fibrous astrocytes in the cellular layer are shown to be significantly increased in the latter group compared to the former.
We measured choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the rat to determine the time course of development, maturity, and senescence of ChAT activity. Tissue was obtained from Sprague-Dawley rats ranging in age from embryonic day 14 through 23 months. Seven regions were examined, including the magnocellular preoptic/substantia innominata region, frontal cortex, medial septal region, hippocampus, diagnoal band, and medial and lateral striatum. ChAT and AChE activities were first detected as early as E18 in the medial septum, diagonal band and magnocellular preoptic area, all regions of cholinergic cell bodies. Enzyme activity subsequently developed in terminal fields of these cholinergic perikarya (hippocampus and frontal cortex) as well as in the striatum. For all regions, enzyme activity rose during the first four postnatal weeks. This increase in enzyme activity was transient and, in most instances, decreases were observed between postnatal days 30 and 60. Most dramatic were the decreases in enzyme activity in the magnocellular preoptic/substantia innominata and diagonal band regions. Age-related declines also occurred in the frontal cortex, hippocampus, magnocellular preoptic/substantia innominata region, and the striatum. Cholinergic systems undergo dynamic changes especially during development and adulthood.
We examined Fisher 344 female rats aged 6, 27, and 33 months old. Prior to sacrifice and morphometric analyses of forebrain cholinergic neurons all rats underwent behavioral characterization in a spatial learning task using the Morris water maze. Performance on the spatial task permitted subsequent grouping of the 27- and 33-month-old animals into impaired or nonimpaired groups. Importantly, the percentage of animals that displayed spatial impairments increased sharply with advancing age. Quantitative assessment of the size and density of choline acetyltransferase (ChAT)-positive neurons throughout the basal forebrain revealed a significant enlargement of forebrain cholinergic neurons within 27-month-old nonimpaired rats compared to 6-month-old rats and 27- and 33-month-old impaired animals. This increase in size was most noted in the medial septum and nucleus of the diagonal band. Significant decreases in the density of ChAT-positive neurons was observed only in the nucleus of the diagonal band of 27-month-old impaired rats compared to 6-month-old controls. Although the significance of enlarged forebrain cholinergic neurons is unclear, we discuss the possibility that within aged rodents neuronal swelling is an active event and represents an early manifestation of the aging process and may constitute a restorative and/or compensatory event in that these rats are relatively asymptomatic with respect to their behavioral deficits. In addition, we discuss in some detail various technical and life effect issues which may vary the outcome of investigations of aged rodents.
In the present study we observed enlarged cholinergic processes in the neocortex of aged Fischer 344 rats. These swollen ChAT-positive profiles appeared either as a single axon enlargement or, in many instances, the bulbous processes coalesced to form grape-like clusters of immunoreactivity. The latter structures looked similar to the immunoreactive profiles observed in the cortex of patients with Alzheimer's disease and in the rat septum following fimbria-fornix transection. Together, these data provide evidence that morphologic changes occur within processes of cholinergic neurons in the aged rat. Moreover, the similarity in appearance between the axonal alterations in the aged rat and in patients with Alzheimer's disease suggests a common pathologic process.
The neocortex receives a major cholinergic innervation from magnocellular neurones in the basal forebrain. However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum. Lesions of this region decrease both AChE and choline acetyltransferase (ChAT) in various forebrain areas, and recent immunohistochemical studies have identified a group of ChAT-containing cell bodies in the midbrain reticular formation and dorsolateral pontine tegmentum. Here we have combined retrograde tracing with ChAT immunohistochemistry to demonstrate that this tegmental cholinergic cell group also directly innervates the cerebral cortex. Other immunohistochemical studies have indicated that the neuropeptide substance P is also present in certain cells in the laterodorsal tegmentum, and these too appear to project to the forebrain. We have therefore performed immunohistochemistry for both ChAT and substance P and have discovered that a subpopulation of the ascending cholinergic reticular neurones contains substance P. Thus, peptide-cholinergic coexistence, previously noted in peripheral neurones, also occurs in the brain.
The acute effects of ultraprofound hypothermia and blood substitution (UHBS) on neuronal cell viability were examined in adult rat hippocampus, a brain region particularly vulnerable to ischemic cell death. UHBS was performed using either artificial cerebrospinal fluid (ACSF) or Hypothermosol, an "intracellular-type" hypothermic preservation solution. After the procedure, the hippocampus was sliced and tested for cellular viability using a combination of cellular fluorochromes that are markers for live cells (acridine orange) and dead cells (propidium iodide). UHBS with ACSF resulted in a variable degree of neuronal death within the hippocampal subfields CA1/CA3, and dentate granular layer and hilus (CA4). In contrast, UHBS with Hypothermosol consistently resulted in hippocampal slices with only mild neuronal death. Our results of preserved hippocampal neuronal viability with use of UHBS and Hypothermosol support the demonstrated central nervous system (CNS) protective effects of UHBS and Hypothermosol when used during prolonged cardiac arrest. The results of this study also suggest that UHBS and Hypothermosol may be useful in the preparation and maintenance of viable hippocampal tissue for physiological studies, especially those involving aged animals, which are particularly vulnerable to hypoxic-ischemic cellular injury
In the present study, we employed a dual-immunofluorescent labeling procedure to determine if the biosynthetic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) are co-localized within neurons in the dorsal medulla of rat. Within this region TH-labeled neurons are distributed within the nuclei of the solitary tracts and medial aspect of the dorsal motor nucleus of the vagus. The absence of dopamine-beta-hydroxylase immunoreactivity within TH-labeled cells in the medial portion of the dorsal motor nucleus of the vagus suggests that these neurons are dopaminergic. Cholinergic perikarya also are present in the dorsal medulla and are distributed throughout the dorsal motor nucleus of the vagus and hypoglossal nucleus. Of these ChAT-positive perikarya, a small percentage limited to the medial aspect of the dorsal motor nucleus of the vagus (i.e., corresponding to the location of dopamine neurons) also contain TH. The existence of TH within ChAT-positive neurons in the dorsal motor nucleus of the vagus provides an anatomical substrate with which to suggest that catecholaminergic and cholinergic fibers contribute to the vagus nerve and may serve to explain some of the cardiac and gastric effects resulting from systemic administration of catecholamine agents.
Nurse executives must challenge basic assumptions about their organizations and help create visions that are feasible and applicable to the institutions' realities. Evaluative criteria and the relationship of the nurse executive to a reality-based model of care are vital to this goal.