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Neurologic injuries are major causes of mortality and morbidity after cardiac surgery. This thesis aimed to investigate cerebral metabolism and perfusion abnormalities in pigs during hypothermic circulatory arrest, selective antegrade cerebral perfusion (SACP) and extracorporeal circulation following progressive venous stasis. Hypothermic circulatory arrest induced a metabolic pattern consistent with overt ischaemia, which was absent following SACP. In contrast, metabolism during SACP was influenced by the perfusate temperature, where a colder perfusate (20 °C) preserved cellular metabolism and membrane integrity better than a warmer perfusate (28 °C). The minimum SACP flow required to maintain metabolism during hypothermia at 20 °C was investigated with magnetic resonance imaging, protein S100β, near infrared spectroscopy and microdialysis. The findings suggested an ischaemic threshold close to 6 ml/kg/min in the present models. Furthermore, regional differences in perfusion with a hemispheric distribution were apparent at all flow levels and differed from earlier studies where the differences were uniform and followed a neuranatomical pattern. Venus stasis following superior vena cava congestion produced measurable signs of impaired cerebral perfusion and patterns of cerebral ischaemia were evident in individual animals. As venous pressure increased, the mean arterial pressure stayed more or less unchanged, generating reduced cerebral perfusion pressure and consequently an increased risk of ischaemia, which may impair cerebral perfusion, especially in cases of compromised arterial flow during extracorporeal circulation. In conclusion, cerebral metabolism and perfusion are influenced by temperature, SACP flow levels and venous congestion. In clinical practice, the regional differences in perfusion during SACP may be of pathogenic importance in focal cerebral ischaemia. Furthermore, the reduced superior vena cava cannula flow may pass undetected during bicaval cardiopulmonary bypass if the superior vena cava flow is not specifically monitored.

Preliminary observations of the restricted regionalization of the enzyme 2' ,3'-cyclic nucleotide-3’ -phosphohydrolase led to an investigation of the subcellular regionalization of this enzyme in cerebral white matter. Since bovine corpus callosum contained eighteen times as much enzyme activity as grey matter, an association of the enzyme with myelin was suggested. Subsequent fractionation of bovine cerebral white matter by sucrose density gradient according to the procedure of Autilio, Norton, and Terry for the purification of myelin (1), showed that greater than 60% of the total activity was associated with the myelin rich fractions. In order to fractionate cerebral white matter more thoroughly, a modified De Robertis fractionation procedure was utilized allowing for separation of nuclear, mitochondrial, and microsomal pellets by differential centrffugation (2). Phosphohydrolase activity was distributed in all fractions, and electron microscopy demonstrated the presence of myelin in all of these fractions. Subsequent fractionation of these primary fractions on a discontinuous sucrose density gradient, showed essentially all of the phosphohydrolase activity in the lightest fraction at the top of each gradient. This band was comprised primarily of myelin figures as verified by electron microscopy. These studies indicated that the enzyme was associated with myelin. The foregoing result was further supported by a study of the increase in enzyme activity during myelination in rats. Myelination is known to occur early in the life of the rat, being initiated a few days after birth, entering a rapid phase of onset at about 10 days and being essentially complete after 50 days (3). Cholesterol was shown to increase in a corresponding manner indicating that myelination was indeed proceeding. Further evidence that the enzyme is associated with myelin came from an investigation of mutant mice. Quaking mice have been shown to be deficient in myelin, containing, according to Bauman and co-workers (4), only 62% of the normal galactolipid levels. Since galactolipids are presently accepted markers for myelin, and since adult quaking mice had 50% of the control enzyme activity, in agreement with the published galactolipid values, it was thought not unlikely that the two phenomena were related. This result also inferred an association of the enzyme with myelin. In attempt to further uncover the physiological role of the 2’,3'-cyclic nucleotide-3'-phosphqhydrolase, investigations have been directed towards elucidation of the substrate specificity of the enzyme. Uridine and guanosine-2’,3'-cyclic phosphothioates, kindly donated by Dr. Fritz Eckstein of the Max Planck Institut für Experimentelle Medizin, were hydrolyzed at rates of l.4 and l4.3% that of adenosine-2’,3'-cyclic phosphate. Cyclic inositol phosphate, synthesized from inositol-2-phosphate in the presence of dicyclohexylcarbodi-imide and pyridine, and glucose-l,2-cyclic phosphate, synthesized from (formula omitted)-D-glucose-l-phosphate, in a similar manner, were not hydrolyzed td any measureable extent. Preliminary results also show that ribose cyclic phosphates are not hydrolyzed, indicating a requirement for a purine or pyrimidine ring in the substrate molecule. These results are discussed with respect to their possible physiological significance. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

In the late nineteenth and early twentieth centuries, French brain and mind scientists filled publications with “case studies” – written works of varying lengths on individual patients or human subjects. This dissertation shows the clinical and conceptual labor that brain and mind scientists employed to transform individual cases into epistemologically meaningful case studies. More specifically, it tracks the rise, fall and afterlife of a model of the case study that emerged in the Salpêtrière in the 1870s and ultimately fell out of scientific favor in the 1890s. In this model, neurologists, psychiatrists and psychologists had a common goal of presenting case study subjects as simple representatives of diseases or faculties of mind, but the strategies they used to attain that goal transformed. Clinicians’ literary strategies for presenting cases as simple gave way to an increasing emphasis on the selection of cases perceived to be inherently simple, particularly in the case studies of neurologist J.M. Charcot and his students. Meanwhile, psychologist Alfred Binet created procedures for generating simplicity experimentally that would impact early intelligence tests, challenging the stability of the distinction between case studies and statistical methods in the brain and mind sciences.

The purpose of the present experiment was to compare the behavioral consequences in rats of lesions of the frontal pole area (FP), the anterior median cortex (AM) described by Leonard, and the caudate nucleus (CN) on a brightness stimulus generalization task. It was hypothesized that deficits in stimulus generalization learning would be demonstrated by rats who received the AM and CN lesions, and that no deficits would be shown by FP lesioned and control (c) animals.

Thesis (MTech (Radiography))--Peninsula Technikon, Cape Town, 2003 / Brain Compatible Learning (BCL), as its name suggests, is a type of learning which is aligned with how the human brain naturally learns and develops. BCL offers many different options and routes to learning as alternatives to conventional 'chalk and talk' methodologies. A BCL curriculum is planned to define the structure and content of a programme of learning, but it also provides opportunities for students to participate in activities, which encourage and enhance the development of an active and deep approach to learning. Using BCL approaches in the classroom thus creates both a stimulating and a caring environment for student learning. This project researches a BCL intervention in a Radiation Science course. The use of BCL techniques has tended to have been done predominantly in the social sciences; this research fills an important 'gap' in the research literature by examining how BCL might be implemented in a technical and scientific context. The research was conducted using an adapted Participatory Active Research methodology in which classroom interventions were planned (within a constructive framework), rather than implemented and then reflected on by all participants. The PAR method was supplemented with a series of detailed questionnaires and interviews. The broad findings of this study relate to students' experiences of BCL in Radiation Science in terms of 'process' and 'product" issues. In terms of process, or the methodology of BCL, students' responses were largely positive.

M.A. / The relatively rapid development of biological approaches to various psychological conditions, has prompted clinicians and researchers to investigate Borderline Personality Disorder more thoroughly. Research has evidenced the uniqueness of Borderline Personality Disorder in terms of description, aetiology and treatment. Of the various aetiologies proposed, the neuropsychological deficit approach is one which is still in its infancy and which may have promise for new treatment strategies. Latest developments delineate neuropsychological deficits in the areas of memory, perception and visuospatial ability. These factors are important for psychotherapeutic purposes. The purpose of this study was to further existing knowledge as regards the aetiology of Borderline Personality Disorder in order to initiate new treatment modalities and management strategies. The study examined whether a battery of neuropsychological tests could detect organic dysfunction in the areas of construction, orientation and attention, memory, perception and concept formation and reasoning in twenty inpatients diagnosed according to DSM-IV criteria, with Borderline Personality Disorder. Two control groups were used, one comprising twenty inpatients diagnosed according to DSM-IV criteria with Personality Disorders from Axis II, Clusters A or C; and the other comprising twenty normal volunteers. Neuropsychological functioning assessed, included measures of attention, construction, visual and auditory-verbal memory, perception, and concept-formation and reasoning. Measurement instruments used in this study included the Digit Symbol subtest of the WAIS-R; Rey Complex Figure; Logical Memory subtest of the WMS-R, Gottschaldt Embedded Figures Test; and the Wisconsin Card Sorting Test. (v) Analysis of variance, multivariate analysis of variance and post hoc tests revealed significant deficits in neuropsychological performance among the borderline personality disorder group and the control group of other personality disorders but not the normal volunteer group. Dysfunction was particularly significant in the areas of attention, visuospatial ability, perceptual organization, and ability to maintain cognitive set. These deficits do not appear to have been attributable to attention deficit disorder, attention deficit hyperactivity disorder, temporal lobe epilepsy, head injury, a concurrent Axis I diagnosis such as major depressive disorder, or current drug and/or alcohol abuse. The observed deficits suggest new ways of understanding the development and maintenance of Borderline Personality Disorder, and provide indications for treatment. In conclusion, it is recommended that full use be made of the measurement instruments used in this study as diagnostic aids to enhance the effectiveness of treatment modalities. It is further recommended that research in this topic be repeated and extended using a larger sample and matched controls.

Long-term adrenalectomy (ADX) results in a specific loss of dentate gyrus granule cells in the hippocampus of adult rats, occurring over a period of weeks to months. This loss of granule cells results in cognitive deficits in a number of tasks that depend on intact hippocampal function. The gradual nature of ADX-induced cell death and the ensuing deficits in cognition are similar to those experienced by patient populations suffering from a variety of pathological conditions. Here we present an animal model by which we use ADX to produce a loss of granule cells within the hippocampus of rats. We also provide experimental evidence for a treatment strategy by which the lost granule cells may be replaced, with the goal of functional recovery in mind. / xii, 191 leaves : ill. (chiefly col.) ; 28 cm

Under de senare åren har det gjorts stora framsteg inom neurologin vad gäller koppling hjärna – inlärning. Tidigare ansågs intelligens vara något bestämt och oföränderligt, men nu hävdar neurologerna att människan själv sätter gränsen för sin intelligens. Alla människor har förmågan att förbättra och utveckla sin intelligens. För att lyckas med detta bör främst två väsentliga faktorer beaktas i skolan: dels att alla är unika och har olika sätt att inhämta information, dels att det är avgörande om människan befinner sig i en stimulerande miljö eller inte. Det är alltså av stor vikt hur skolmiljön ser ut för våra elever för bästa möjliga inlärning. Jag vill med detta arbete visa att genom att förstå vilka principer som styr hjärnans funktioner kan vi lärare bli bättre på att lära våra elever att lära. Studien belyser dels hjärnans uppbyggnad och vad den har för koppling till och betydelse för inlärningen, dels belyser jag tre olika inlärningsteorier och ger praktisk/pedagogiska exempel på hur de kan användas i en klassrumssituation.

The brain has been one of the central foci in studies of vertebrate evolution. Work in East African cichlids and other emerging fish models like the Mexican cavefish (Astyanax mexicanus) offer new insight on the role of patterning on brain evolution. These fish can be grouped into two major categories according to habitat; for cichlids it is rock-dwelling (known locally as mbuna) and sand-dwelling (non-mbuna) lineage. The brain development of mbuna versus non-mbuna is defined by changes in gene deployment working along the dorsal/ventral (DV) and anterior/posterior (AP) neuraxes, respectively. Comparison of disparate fish ecotypes offer a new perspective of the role of patterning on brain evolution; through the slight and early modification of signal pathways working across 3-D axes, and a subsequent magnifying effect across ontogeny, evolution can generate widespread changes in the brain. To illustrate this patterning model of brain evolution, two comparative studies were done between mbuna and non-mbuna, examining the action of gene pathways that work to pattern the cichlid forebrain. The first study found that non-mbuna cichlids have a more rapid AP expansion of a gene pathway (Wingless) into the presumptive midbrain and diencephalon versus mbuna. These forebrain structures are involved in sight processing and could be of ecological benefit to vision-focused non-mbuna. The second study described a difference within the developing telencephalon. The embryonic telencephalon is split into the pallium, which processes visual signals, and the subpallium, which develops into the olfactory bulbs. Mbuna possess a larger subpallium relative to non-mbuna, which have a larger pallium. This was correlated to a more rapid expansion of another gene pathway (Hedgehog) along the DV axis. The difference in size of the pallial vs. subpallialial comparments between cichlids can be correlated to expanded olfaction in mbuna and vision in non-mbuna adult brains. Overall, East African cichlids are an excellent system to investigate the role of patterning on brain evolution because they allow for the comparison of the earliest patterning events in brain ontogeny between distinct ecotypes. These fish systems link study in brain development to the brain morphology comparisons employed in classic studies of brain evolution.