Thesis (M.S.)--University of Wisconsin--Madison, 1981. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 296-298).

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN

The pineal complex of rodents is made up of a pineal organ which developmentally always originates from the area between the habenular and posterior commissure and a pineal sac which is continuous with the choroid plexus of the third ventricle. This sac appears to be identical to the choroid plexus at both light and electron microscopic levels. The pineal sac abuts the deep and superficial pineal organs of the golden hamster. In the PET mouse, gerbil, kangaroo rat and Chinese hamster, the sac is contiguous with only small areas of pinealocytes. This sac never abuts true pineal parenchyma in the albino rat. The variability of the relationship between this sac and pineal parenchyma indicates that this structure may not be the main physiological route of pineal gland secretion. The ultrastructure of pinealocytes from normal and blinded PET mice and normal and blinded gerbils indicate s the possibility of secretory activity in pinealocytes. Pinealocytes in the PET mouse have many dense core vesicles which can be found in the perykaryon, processes, and polar terminals of the cells which end in a pericapillary space. This space is near a fenestrated capillary. The possibility exists that these dense cored vesicles may be extruded from the cell terminals and pass into the fenestrated capillaries. Such fenestrated capillaries commonly are found in endocrine organs. The gerbil pinealocyte has two types of granules. Their nature is unknown, and the relationship between the two is uncertain. Small granules, resembling the small granules in gerbil pinealocytes in size and density, can be found in intercellular and pericapillary spaces. The relationships between these two granules is equally in doubt. The ultrastructure of pinealocytes of PET mice and gerbils reflects changes with blinding. Pinealocytes of blinded PET mice are more vesiculated and have greater numbers of lipid droplets. The pineal glands of those blinded gerbils, which were known to be highly functional by their physiological effects on the gonads, contained large electron dense structures. They were found in unidentified cell processes, interstitial cells, and pinealocytes. Pineal glands from a greater number of animals will have to be studied and compared with those of the same species reflecting low pineal activity in order to verify the relationship between pineal activity and these large electron dense structures. Histochemical analyses would be essential to identify and to clarify the relationships and activities among these vesicles, granules, and electron dense structures in pinealocytes of PET mice and gerbils. Blinding of the golden brown hamster and the gerbil resulted in a significant decrease of testis and seminal vesicle weight. This effect in the gerbil occurred during the fall season but when repeated during the winter season resulted only in the decrease of seminal vesicle weight. Female gerbils, however, responded to blinding by a decrease in ovarian and uterine weights during the winter season but only in uterine weight during the fall season. All of these effects of a lack of light on the gonads were prevented if the animals were also pinealectomized. The effects of olfactoriectomy which resulted in a decrease in seminal vesicle weight in one series of gerbils could also be overcome by pinealectomy. The pineal gland then may be responsible for production of an antigonadic substance. with the pineal gland removed the antigonadic source is removed, and the testis and/or seminal vesicle weights remain normal. A lack of light appears to stimulate the pineal gland to function since pinealectomy alone did not effect an increase in reproductive organ size in any of the animals which we studied. The albino rat and PET mouse did not respond to a lack of light as did the hamster and gerbil. Moreover, in the PET mouse, blindness did not affect prepubertal or postpubertal animals, adults during different seasons of the year, or adults treated neonatally with testosterone propionate. Female PET mice and male wild mice were equally unaffected. An effect of the pineal gland on the pituitary gland and adrenal gland is doubtful. Animals with or without a pineal gland exhibited no difference in pituitary or adrenal weights. More sensitive techniques will have to be employed to determine pineal-pituitary and pineal-adrenal interactions.

The pathology which results from traumatic brain injury (TBI) have long been believed to be immediate and irreversible. However, recently it has been shown that, although the primary effects are virtually unavoidable, the secondary effects manifest themselves through biochemical processes set in motion at the time of the injury. These events are frequently mediated through the process of excitotoxicity, which results from a widespread release of excitatory neurotransmitters. These neurotransmitters go on to activate both ionotropic and metabotropic receptors. The signal transduction initiated through these receptor populations gives rise to changes in gene expression. One result of this release of neurotransmitter is an influx of calcium by means of excitatory receptors on the cell. The neurotransmitters upon which most research is focused are glutamate, aspartate, and acetylcholine. Current research is aimed at investigating antagonists to this process as well as elucidating steps within the process. Antagonists primarily function to reduce the calcium toxicity through modulation of receptor activity. However, the therapeutic window for effective antagonist usage is short. Therefore, although they may represent a viable treatment option, they need to be administered as early as possible following the injury to have the greatest effect. The purpose of this paper is to provide a summary of the available literature on TBI and excitotoxicity with a focus on changes in gene regulation. This paper will summarize information on the steps inVolved in the intracellular signaling cascade following brain injury and provide insight to further sites for regulation and treatment. This will also allow for development hypotheses on the possible roles of some of the genes whose expression is already known to be altered.

The suppression of the immune response in senescent animals, including humans, is not complete and may be ameliorated by specific interventions. Previous studies have suggested that the replacement of thymus factors lost with age may rejuvenate senescent immune function. Similarly, exogenous growth hormone has been reported to improve senescent immune function in certain mammals. Other studies with the immunomodulator PSK claim to restore tumor-induced immunosuppression even in aged mice. This project investigated the abilities of thymus supernatant, ovine growth hormone, and PSK to rejuvenate different parameters of the senescent immune response. In the first series of experiments, erythroid depleted bone marrow cells from 3 month and 24 month old CBA (Thy 1.2) mice were given to irradiated ARR (Thy1.1) mice and allowed to repopulate for 30 days. Flow cytometry analysis using x mAb Thy 1.1 and Thy 1.2 revealed that the old bone marrow was deficient in its ability to repopulate the thymus. Subsequent experiments revealed that treatment of the old bone marrow with thymus supernatant, made from neonatal thymus cultures, could restore the thymus repopulating ability of these cells. The second part of this project investigated the reported ability of growth hormone to rejuvenate the age-involuted thymus and senescent immune response. Limited success was achieved using subcutaneous timed-release pellets containing ovine growth hormone. Twenty-four month old mice treated in this manner for 8 weeks demonstrated larger thymuses with nearly normal thymus morphology, i.e. distinct cortical and medullary regions. Various assays of cellular immune function exhibited no improvement. PSK injections every other day injections of 18 month old mice, for one month, resulted in an increase in splenic mass when compared to saline treated age—matched controls. There was no improvement in the thymus morphology or in the cellular immune function of the treated animals.

While it is well known that the different sensory modalities are primarily represented at separate locations within the central nervous system, there are numerous sites in which information from the different sensory modalities converge. Perhaps the best known structure where inputs from different sensory modalities converge is the superior colliculus. Here, not only are visual, auditory and somatosensory inputs present, but they also form organized representations of auditory and visual space as well a map of the body surface in addition, neurons that receive inputs from more than one sensory modality (i.e. multisensory) are found here in abundance. Although a great deal is known regarding the physiological properties of these multisensory neurons and how these characteristics apply to multisensory neurons elsewhere in the brain, little is known regarding the anatomical basis for multisensory convergence and integration. Therefore, the present study is focused on the following problem: How does the organization of the inputs from different sensory modalities to the deep layers of the superior colliculus relate to the multisensory nature of its constituent neurons?

The tau mutation affects the circadian system of the golden hamster primarily by decreasing the period of the activity cycle from 24 to 20 hours. To study the effect of this mutation on reproductive function in the golden hamster, 3 experiments have been designed. In the first experiment, wild-type and tau female hamsters will be maintained in conditions of 14:10 LD and 11.7:8.3 LD, respectively. Blood samples will be taken and analyzed by radioimmunoassay (RIA) to determine the timing of the proestrus LH surge. In the second experiment, wild-type and tau males will be transferred to shortened photoperiods of 10:14 LD and 8.3:11.7 LD, respectively, and testicular length and width will be used as a measure of the onset of testicular regression and subsequent recrudescence. In the final experiment, wild-type and tau females will be transferred to conditions of 10:14 LD and 8.3:11.7 LD, respectively, and the time to the onset of anestrus will be recorded. It is expected that in the tau females, the preovulatory LH surge will occur 8.4 hours after lights-on. The onset of gonadal regression, recrudescence, and anestrus will occur 16.7% [(24 hours - 20 hours)/24 hours] sooner in the mutant hamster when measured in absolute time. When the time to the onset of these processes is measured in light cycles, however, it is probable that these events occur within the same number of light cycles in both the wild-types and the tau hamsters. The basic hypothesis is that the main impact of the tau mutation will be on the timing of these specific reproductive phenomena, but the fundamental physiological characteristics of these events will remain unaffected. These results would suggest that the timing of the preovulatory LH surge and the occurrence of gonadal regression, recrudescence, and anestrus in a shortened photoperiod are driven by the same neural oscillator that regulates the period of the activity cycle in the golden hamster.

Radiosurgery using the Linear Accelerator or the Gamma Knife has proven to be an effective treatment modality for malignant brain tumors. In comparison to other treatments, radiosurgery can be performed on an outpatient basis and is noninvasive (Table 5). Due to the functional properties of radiosurgical devices, they are ideal for patients who are unable to undergo surgical removal of their brain tumors. The sharp dose drop—off beyond the tumor margin allows for high dosage tumor irradiation while sparing normal brain tissue. Many procedures that involve radiosurgery use it as a ”boost” therapy in conjunction with surgical resection and whole brain irradiation. ”Boost" therapy enhances the standard treatment procedure for malignant brain tumors. Unfortunately, radiosurgery is not always able to halt the progression of malignant brain tumors. Patients with metastatic brain tumors usually succumb to systemic disease. Patients who have gliomas generally die due to the inability of local tumor control. However, the use of radiosurgery can contribute to increasing a patient’s quality of life. Often, treatment is followed by a decrease in corticosteroid administration and an improvement in a patient's neurological status. The future directions of radiosurgery could include the development and implementation of a randomized studies to determine a dose-volume protocol for gliomas and the different forms of metastases. Also, an investigation should be undertaken to determine whether the use of high (50 Gy or more) radiosurgical doses as the only treatment for gliomas and cerebral metastases would prove to be a more effective use than ”boost” therapy.

he use of evoked potentials to evaluate the functional integrity of neuronal pathways has become a useful and accepted practice in clinical medicine. The use of visual evoked potentials for assisting in the diagnosis of such diseases as optic neuritis and multiple sclerosis is also well recognized. However, the visual evoked potential, unlike the auditory evoked potentials, lacks a well defined electrophysiological to neuroanatomical correlation; especially that of a significant non-cortical component. Currently, visual evoked potentials rely principally on the measurement of a cortical (occipital) positive peak of activity at 100ms (P100), recorded with a single channel electrode system, to evaluate pathway integrity. In this study, visual evoked potentials were recorded using a three-channel, orthogonal co-ordinate system which we have designated "vector" visual evoked potentials (VVEP). This method allows the generated evoked response to be plotted on a three dimensional co-ordinate system with respect to time. Through the use of pattern reversal of a checkerboard pattern, in full and hemi retinal field stimulation, reproducible activity both prior to and afier the P100 wave was demonstrated. In particular, activity found at approximately 55ms is believed to be generated from the Lateral Geniculate Body. Furthermore, because this method summarizes the activity of the entire brain for a given time, as opposed to the single channel recording, a great deal of information about the entire visual pathway can be suggested. Finally, anatomical correlates to discrete activities identified by this method can be made.

As computers become an increasingly important part of medical education, a proper understanding of the techniques and applications of computer aided modeling is vital. An initial overview of medical imaging and the techniques of computer modeling is presented. Construction of three-dimensional models of anatomical structures is then discussed in great detail with specific focus on modeling structures like the inguinal canal. The inguinal canal is one region where computer modeling efforts should be directed because it presents a special challenge. Understanding the walls, borders and layering of the inguinal canal is especially difficult but vital to accurate clinical diagnoses of hernias. Computer-based instruction based on high-quality three dimensional images promises to greatly enhance students’ learning and comprehension of difficult anatomical structures and relationships.