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Biomedical subjects

L E Harrell

Publications and source records attributed to L E Harrell.

At least 73 records · Page 4Linked to original sources
PubMed1988

The role of cortical sympathetic ingrowth in the behavioral effects of nucleus basalis magnocellularis lesions.

Following cholinergic denervation of the neocortex by nucleus basalis magnocellularis (NBM) lesions, peripheral sympathetic fibers grow into the neocortex. Two experiments were performed to determine the behavioral effects of this neuronal rearrangement. Group I animals underwent training on a standard radial-8-arm maze task, while Group II animals learned a modified version (i.e. 4 arms baited). Following acquisition, NBM lesions were performed. Animals with lesions but without sympathetic ingrowth performed consistently better in both behavioral paradigms, than animals with NBM lesions and sympathetic ingrowth. These studies suggest that cortical sympathetic ingrowth can alter behavior and is detrimental to the learning of a spatial memory paradigm.

Acetylcholinesterase↗
PubMed1988

Role of gender in the behavioral effects of peripheral sympathetic ingrowth.

Following cholinergic denervation of the hippocampal formation, peripheral sympathetic nerves originating from the superior cervical ganglia grow into the hippocampus. As gender is known to alter the anatomy of hippocampal sympathetic ingrowth, we assessed the effect of this variable on the behavioral recovery following ingrowth. Adult male or female rats were trained on a standard version of a radial-8-arm maze task until they reached a specific learning criterion. Animals from each sex then underwent one of three surgical procedures: sham surgery, medial septal lesions plus superior cervical ganglionectomy, or medial septal lesion plus sham ganglionectomy. Reacquisition of the maze was then assessed. Prior to surgery, male animals acquired the task significantly faster than female animals. Following surgery male and female rats recovered overall performance at similar rates. However, marked group differences were observed. In males, the control group recovered faster than the group with medial septal lesion plus ganglionectomy, which recovered faster than the medial septal lesion group. In females, the control group recovered faster than the medial septal lesion group, which in turn recovered faster than the medial septal ganglionectomy group. The results of this study clearly demonstrate that gender can influence the behavioral effects of hippocampal sympathetic ingrowth. We believe that this is the first report in which gender has been shown to alter the behavioral effect of a neuronal reorganization.

Animals↗
PubMed1988

Chronic, oral aluminum administration to rats: cognition and cholinergic parameters.

Administration of aluminum sulfate in the drinking water of male Sprague-Dawley rats for thirty days resulted in an impairment of both consolidation and extinction of a passive avoidance task. No impairment of performance was observed on an active avoidance task, radial arm maze or open field activity measure. Biochemical analysis indicated a slight (less than 10%) but significant increase in hippocampal muscarinic receptor number after aluminum treatment as determined by tritiated quinuclidinyl benzilate (3H-QNB) binding. No changes were found in choline acetyltransferase (ChAT) activity, phosphoinositide hydrolysis, 3H-QNB binding in the cortex or tritiated pirenzepine (3H-PZ) binding in the hippocampus or cortex. These results indicate that cholinergic degeneration was not the cause of the observed cognitive impairments.

Administration, Oral↗
PubMed1987

Alterations in regulatory behaviors induced by medial septal lesions and superior cervical ganglionectomy.

Following medial septal (MS) lesions peripheral sympathetic fibers, originating from the superior cervical ganglia (SCG), grow into the hippocampus and habenula. To assess their effect on regulatory behaviors, body weight, and food and water consumption were studied under ad libitum and pharmacological stress conditions, after MS lesions, superior cervical ganglionectomy (Gx) or MS lesion + ganglionectomy (MSGx). Twenty-two animals completed the study: control (n = 7), MS lesion (n = 5), Gx (n = 6), MSGx (n = 4). No differences were observed preoperatively. Postoperatively, body weight fell but over time all groups gained weight. However, animals with MSGx were lighter than MS or Gx animals (which were equivalent), which in turn were lighter than controls (P less than 0.0001). Hypophagia was observed in the Gx and MSGx animals when compared to the MS and control groups (P less than 0.05), while hyperdipsia was seen in the MS and Gx groups (P less than 0.001). Administration of both 1 M NaCl and isoproterenol (25 micrograms/kg) increased drinking in all animals (P less than 0.001), with the MSGx group consuming significantly less than all others (P less than 0.025). Food intake increased following 2-deoxy-D-glucose (500 mg/kg) (P less than 0.0001), while epinephrine (120 micrograms/kg) treatment produced anorexia only in the MS group (P less than 0.05). Hyperthermia was found in the Gx and MSGx groups. The results of this study suggest that both the MS region and SCG contribute to the maintenance of normal regulatory behaviors, with combined loss of these neural systems resulting in severe disturbances, both qualitatively and quantitatively different from either MS lesion or Gx. Although the MS lesion group clearly regulated better than the MSGx group, it is unclear whether this is due to ingrowth or just the presence of the SCG.

Acetylcholinesterase↗
PubMed1987

Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions.

To assess the potential usefulness of chronic acetylcholinesterase inhibition in the treatment of learning/memory disorders arising from central cholinergic deficient states, physostigmine was administered chronically to rats with medial septal lesions and the retention of a spatial/working memory task investigated. Three dose levels of physostigmine (0.025, 0.05, 0.075 mg/kg) were administered three times per day following medial septal lesions. Retention of a standard radial 8-arm maze task was assessed. Although the lesions transiently disrupted task performance, physostigmine therapy did not improve either daily performance or total recovery time. Our results suggest that chronic acetylcholinesterase inhibition is not effective in ameliorating the working memory deficits that occur after medial septal lesions.

Animals↗
PubMed1987

Passive-avoidance learning after medial septal lesions: effect of experience and the peripheral sympathetic nervous system.

Prior studies from our laboratory suggest that peripheral sympathetic ingrowth, which occurs in the hippocampus following medial septal lesions, is detrimental to the reaquisition of a spatial learning/memory task. To assess the generality of this finding we studied step-through passive-avoidance learning in animals with a medial septal lesion with or without superior cervical ganglionectomy under two experimental conditions. In the first condition, in which no prior experience with the task occurred, animals with a lesion demonstrated facilitation of learning. In the second condition, in which animals received pretraining with no shock prior to surgical manipulation, the behavior of animals with the lesion was similar to that of controls. No effect of ganglionectomy or initial sympathetic ingrowth was found in either condition. The results suggest that the effects of medial septal lesions on passive avoidance behavior are determined by the experimental condition and that early peripheral sympathetic ingrowth does not contribute either in a detrimental or beneficial fashion to passive avoidance learning.

Animals↗
PubMed1987

Cholinergic neurons, learning, and recovery of function.

Two experiments were designed to examine the role of the cholinergic septo-hippocampal projection in spatial and nonspatial learning processes. In Experiment 1 the interaction of individual learning strategies and recovery of function was investigated following medial septal lesions, by assessing individual learning styles and number of trials to recovery on a standard radial eight-arm-maze task. Experiment 2 addressed the relevance of the cholinergic septo-hippocampal pathway in the acquisition of spatially mediated behavior, by employing medial septal lesions, prior to acquisition learning of a modified version of the radial eight-arm-maze task. The data from these two experiments demonstrated that (a) the cholinergic septo-hippocampal projection is important for the acquisition and maintenance of spatial learning strategies, (b) loss of cholinergic function leads to alteration of learning strategies, (c) different learning strategies can be employed to acquire the same behaviors, and (d) the rate of recovery following brain injury can be influenced by preoperative learning strategies.

Animals↗
PubMed1987

Magnetic resonance imaging and the diagnosis of dementia.

We describe seven patients with clinical, laboratory, and CT evidence of primary degenerative dementia (Alzheimer's, Pick's). Magnetic resonance imaging demonstrated regions in the white matter consistent with cerebral infarction. MRI may be a sensitive way to differentiate multi-infarct dementia and primary degenerative dementia.

Aged↗
PubMed1986

Peripheral sympathetic ingrowth can alter metabolic activity within the hippocampal formation.

After cholinergic denervation of the hippocampal formation, peripheral sympathetic fibers arising from the superior cervical ganglia grow into the dentate gyrus and CA3 region; the functional significance of sympathetic ingrowth into the hippocampal formation is unknown. Utilizing electrical stimulation of the preganglionic trunk in combination with 2-deoxy-D-[3H]-glucose fine-grained autoradiograms, we demonstrated an alteration of hippocampal glucose metabolism, suggesting that this neuronal rearrangement makes functional connections within the hippocampus.

Animals↗
PubMed1985

Cholinergic influences on hippocampal glucose metabolism.

2-Deoxy-D-[3H]glucose autoradiography was employed to investigate the effects of acute cholinergic manipulations on hippocampal glucose metabolism. In general, manipulations designed to reduce cholinergic activity (medial septal ablation, atropine treatment) reduced hippocampal glucose metabolism. Maximal decrements were found in the terminal fields of the septohippocampal projection after medial septal lesions, while maximal deficits after atropine treatment correlated with muscarinic receptor binding. Electrical stimulation of the medial septum resulted in increased glucose utilization in some terminal fields of the septohippocampal projection and decreased utilization in the terminal fields of the perforant pathway. Our data clearly indicate that acute alterations in cholinergic activity can affect hippocampal glucose metabolism but the distribution, direction and degree of these changes is dependent on the specific treatment.

Animals↗
PubMed1984

Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.

To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.

Animals↗
PubMed1984

Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism.

Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[3H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity.

Acetylcholine↗
PubMed1984

Motor neuron disease presenting with respiratory failure. Report of two cases.

In the two cases reported here, acute respiratory failure developed as a manifestation of motor neuron disease (amyotrophic lateral sclerosis). Both patients complained of systemic weakness before respiratory failure occurred. In one patient, respiratory support could not be discontinued because of poor inspiratory and expiratory pressure. Although acute respiratory failure is an uncommon manifestation of motor neuron disease, we believe this disorder should be considered in patients with unexplained respiratory failure and in those who cannot be weaned from a respirator for mechanical reasons.

Aged↗
PubMed1983

Sympathetic sprouting and recovery of a spatial behavior.

After lesions of the medial septum, peripheral sympathetic fibers from the superior cervical ganglion appear in the hippocampal formation. To assess the functional significance of this neuronal rearrangement, we analyzed behavior on a spatial/memory task sensitive to hippocampal dysfunction, the radial eight-arm maze. The procedure allowed evaluation of both working and reference memory. All rats were able to master the task. Half of the rats then underwent either medial septal lesions and ganglionectomy or sham neurosurgery and ganglionectomy, and the other half underwent medial septal lesions or sham neurosurgery followed by ganglionectomy after further behavioral testing. Medial septal lesions in both groups disrupted taks performance with recovery of performance occurring with time. However, the rate of recovery was significantly enhanced in rats which had septal lesions and ganglionectomies simultaneously. Removal of the ganglion after recovery produced no effects on maze performance. Our results suggest that sympathetic ingrowth retards recovery processes.

Animals↗
PubMed1983

Pneumocephaly from epidural anesthesia.

An elderly woman who had spinal epidural anesthesia thereafter had headache, anorexia, nausea and vomiting, dehydration, seizures, and cardiovascular collapse. CAT scan revealed air in the posterior fossa, probably caused by intradural injection of air during epidural anesthesia. We propose that this may be an occasional cause of headache or more substantial complications after epidural anesthesia, and suggest that CAT scanning may be helpful in identifying this complication.

Amputation, Surgical↗
PubMed1983

Hand weakness in the elderly.

Hand weakness is an important but frequently overlooked problem in the elderly. The exact diagnosis is often difficult because of the complexities of innervation and muscle function. An anatomic approach to the diagnosis of isolated hand weakness in the elderly is presented. Causes, evaluation, and therapy for various forms of this symptom are reviewed.

Aged↗
PubMed1978

Organismic states and their effect on recovery from neurosurgery: a new perspective with implications for a general theory.

The authors examine and review current research on recovery of function following brain damage. Emphasis is placed upon the physiological and neurochemical states of the organism prior to neurosurgery and their influences on behavioral recovery of function. It is proposed that the consequences of a given neurosurgical procedure depend not only on its neuroanatomical locus but also on the organismic state of the brain substrate at the time of such a procedure. The brain substrate can be modified prior to a given manipulation, resulting in an alternation of the effects of the manipulation. The implications of this new perspective for both basic research and clinical medicine are discussed.

Animals↗