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PubMed1987

The effect of hypoxia on traumatic head injury in rats: alterations in neurologic function, brain edema, and cerebral blood flow.

We evaluated the effects of early posttraumatic hypoxia on neurologic function, magnetic resonance images (MRI), brain tissue specific gravities, and cerebral blood flow (CBF) in head-injured rats. By itself, an hypoxic insult (PaO2 40 mm Hg for 30 min) had little effect on any measure of cerebral function. After temporal fluid-percussion impact injury, however, hypoxia significantly increased morbidity. Of rats subjected to impact (4.9 +/- 0.3 atm) plus hypoxia, 71% had motor weakness contralateral to the impact side 24 h after injury, while only 29% of rats subjected to impact alone had demonstrable weakness (p less than 0.05). Lesions observed on MR images 24 h after injury were restricted to the impact site in rats with impact injury alone, but extensive areas with longer T1 relaxation times were observed throughout the ipsilateral cortex in rats with impact injury and hypoxic insult. Brain tissue specific gravity measurements indicated that much more widespread and severe edema developed in rats with impact injury and hypoxia. [14C]Iodoantipyrine autoradiography performed 24 h after injury showed that there was extensive hypoperfusion of the entire ipsilateral cortex in rats with impact injury and hypoxia. These results show that large areas of impact-injured brain are extremely vulnerable to secondary insults that can irreparably damage neural tissue, and provide experimental evidence for the observed adverse effects of hypoxia on outcome after human head injury.

Animals↗
PubMed1992

Dependency on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine.

Concomitant intracerebroventricular (i.c.v.) injection of anti-arginine vasopressin (AVP) antiserum dose-dependently suppressed the development of analgesic tolerance to daily morphine, 10 mg/kg, s.c., in mice. This suppressive effect of the antiserum was reduced by incubating the antiserum with AVP in vitro, before i.c.v. injection, suggesting that the antiserum inactivates brain AVP to result in the suppression of the development of tolerance in vivo. Similar to the antiserum, both AVP V1 and V2 antagonists given i.c.v., 10 ng and 20 ng/mouse, respectively, suppressed the development of morphine tolerance. Meanwhile, the administration of antiserum dose-dependently recovered morphine analgesia in morphine-tolerant mice and a complete recovery of analgesia was observed at the highest dose of antiserum following the second injection, and the effect of antiserum was maintained for 3 days after its withdrawal. Likewise, 10-100 ng/mouse of AVP V1 receptor antagonist given i.c.v. recovered morphine analgesia partially but significantly in a dose-dependent manner; however, AVP V2 receptor antagonist at the same doses partially recovered analgesic effect but the effect was neither significant nor dose-dependent. These findings suggest that the tolerance developed to morphine can be reversible when disturbing the function of brain AVP, but in addition to the different mechanisms of antiserum, V1 and V2 receptor antagonists, the V1 receptor-mediated mechanism may be more closely concerned in this phenomenon.

Angiotensin Receptor Antagonists↗
PubMed1986

A brief history of the influence of trace elements on brain function.

From this brief review of history it is evident that lead, mercury, iodine, cobalt, iron, copper, manganese, and zinc have important influences on brain development and function. Identity of thresholds at which effects occur is needed for determination of safe and/or essential levels of these elements in diets. Such knowledge will help define human needs for essential elements, and the hazards of toxic elements.

Animals↗
PubMed1997

Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: application to functional brain imaging.

Perfusion is a crucial physiological parameter for tissue function. To obtain perfusion-weighted images and consequently to measure cerebral blood flow (CBF), a newly developed flow-sensitive alternating inversion recovery (FAIR) technique was used. Dependency of FAIR signal on inversion times (TI) was examined; signal is predominantly located in large vessels at short TI, whereas it is diffused into gray matter areas at longer TI. CBF of gray matter areas in the human brain is 71 +/- 15 SD ml/100 g/min (n = 6). In fMRI studies, micro- and macrovessel inflow contributions can be obtained by adjusting TIs. Signal changes in large vessel areas including the scalp were seen during finger opposition at a TI of 0.4 s; however, these were not observed at a longer TI of 1.4 s. To compare with commonly used BOLD and slice selective inversion recovery techniques, FAIR and BOLD images were acquired at the same time during unilateral finger opposition. Generally, activation sites determined by three techniques are consistent. However, activation of some areas can be detected only by FAIR, not by BOLD, suggesting that the oxygen consumption increase couples with the CBF change completely. Relative and absolute CBF changes in the contralateral motor cortex are 53 +/- 17% SD (n = 9) and 27 +/- 11 SD ml/100 g/min (n = 9), respectively.

Brain↗
PubMed1986

[Effects of Ginkgo biloba extract on functional brain activity.. An assessment of clinical and experimental studies].

Electroencephalography is the only convenient method for functional exploration of the brain. The recent introduction of signal analysis techniques has given it a quantitative dimension and has resulted in pharmacological studies of electoencephalograms. In four studies of this kind the effects of Ginkgo biloba extract were investigated on three pathological animal models, in young healthy volunteers and in elderly people with dementia disorders. In man, the EEG tracings could be analyzed in relation to different psychometric tests. The results obtained confirm those of clinical trials, and notably the activity of Ginkgo biloba extract on alertness.

Adolescent↗
PubMed1999

Laterality in functional brain imaging studies of schizophrenia.

Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.

Brain↗
PubMed2006

Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints. METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures. CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

Adult↗
PubMed2004

Comparisons of Korsakoff and non-Korsakoff alcoholics on neuropsychological tests of prefrontal brain functioning.

BACKGROUND: Evidence suggests that alcoholics exhibit particular deficits in brain systems involving the prefrontal cortex, but few studies have directly compared patients with and without Korsakoff's syndrome on measures of prefrontal integrity. METHODS: Neuropsychological tasks sensitive to dysfunction of frontal brain systems were administered, along with standard tests of memory, intelligence, and visuospatial abilities, to 50 healthy, abstinent, nonamnesic alcoholics, 6 patients with alcohol-induced persisting amnestic disorder (Korsakoff's syndrome), 6 brain-damaged controls with right hemisphere lesions, and 82 healthy nonalcoholic controls. RESULTS: Korsakoff patients were impaired on tests of memory, fluency, cognitive flexibility, and perseveration. Non-Korsakoff alcoholics showed some frontal system deficits as well, but these were mild. Cognitive deficits in non-Korsakoff alcoholics were related to age, duration of abstinence (less than 5 years), duration of abuse (more than 20 years), and amount of alcohol intake. CONCLUSIONS: Abnormalities of frontal system functioning are most apparent in alcoholics with Korsakoff's syndrome. In non-Korsakoff alcoholics, factors contributing to cognitive performance are age, duration of abstinence, duration of alcoholism, and amount of alcohol consumed.

Adult↗
PubMed2001

Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease.

To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions.

Aged↗
PubMed1993

Prognosis of myocardial infarction and brain functional asymmetry.

Seventy-eight men (mean age, 47.0 +/- 1.1 years) who had suffered from myocardial infarction were examined. Blood cholesterol, lipoproteins, triglycerides, insulin and cortisol concentrations were compared in patients with left hemisphere or right hemisphere cerebral dominance. Patients with left hemisphere dominance had more serious disease and much higher levels of blood cholesterol and lipoproteins. Patients with right hemisphere dominance had the highest levels of blood cortisol and insulin. The brain's functional asymmetry may be one of the risk factors for coronary atherosclerosis in subjects under the age of 50 years.

Cholesterol↗
PubMed2006

Direct regulation of adult brain function by the male-specific factor SRY.

The central dogma of mammalian brain sexual differentiation has contended that sex steroids of gonadal origin organize the neural circuits of the developing brain. Recent evidence has begun to challenge this idea and has suggested that, independent of the masculinizing effects of gonadal secretions, XY and XX brain cells have different patterns of gene expression that influence their differentiation and function. We have previously shown that specific differences in gene expression exist between male and female developing brains and that these differences precede the influences of gonadal hormones. Here we demonstrate that the Y chromosome-linked, male-determining gene Sry is specifically expressed in the substantia nigra of the adult male rodent in tyrosine hydroxylase-expressing neurons. Furthermore, using antisense oligodeoxynucleotides, we show that Sry downregulation in the substantia nigra causes a statistically significant decrease in tyrosine hydroxylase expression with no overall effect on neuronal numbers and that this decrease leads to motor deficits in male rats. Our studies suggest that Sry directly affects the biochemical properties of the dopaminergic neurons of the nigrostriatal system and the specific motor behaviors they control. These results demonstrate a direct male-specific effect on the brain by a gene encoded only in the male genome, without any mediation by gonadal hormones.

Animals↗
PubMed2002

The percussion reactions involved in brain function.

A hypothesis is presented describing the operation of mammalian brains on the basis of rapid percussion chemical reactions and shock waves generated by such reactions. It is shown that the products of these are various chemical compounds identified as present in the brain. The manner in which the brain deals with various external optical, sonic pressure, and chemical phenomena is described. The origin and possible relief of disabling conditions related to brain action are discussed on the basis of the hypothesis.

Animals↗
PubMed1976

Two biological rhythms of perception distinguishing between intact and relatively damaged brain function in man.

A simple test of perception, the Critical Flicker Fusion threshold (CFF) was given successively for 20 mins. to 69 healthy subjects aged 7-63 and to 53 comparable neuropsychiatric patients. The latter could be divided into a functionally sick group and a group with brain damage. Auto-correlation analysis revealed significant sine-wave cycles of amplitude and ultradian frequency for the CFF mean scores and the CFF "Scatter* scores. Both cycles of recurrence showed frequencies which distinguished significantly between the total healthy subjects and the patients. Further analysis showed no difference between controls and emotionally sick patients (i.e. those with sociopathy, schizophrenia and manic depressive psychosis) but there was a highly significant difference between these three groups and patients with relatively damaged C.N.S. (i.e. those with mental deficiency, organic brain syndrome and organic dementia). Even among the control group a progressive increase in frequency of these perceptual cycles occurred with advancing age. These CFF results point to the existence of a cycle of perceptual acuity and another of vigilance in the organism. Both appear to relate to the neural integrity of the C.N.S.

Adolescent↗
PubMed1994

Perturbation of thyroid hormone homeostasis in the adult and brain function.

Although a critical role of thyroid hormones in mammalian brain development is well established and extensively documented, the adult CNS is often thought to be a thyroid hormone-insensitive organ. The presence in the adult brain of thyroid hormone, along with high levels of nuclear T3 receptors and the strict regulation of intracerebral T3 levels, coupled with overt psychomotor and cognitive dysfunctions in adult-onset dysthyroidism, casts doubt upon this assumption. We have therefore investigated the influence of thyroid hormones on the biochemistry, metabolism and molecular biology of adult rat brain regions and confluent neurons and astrocytes in culture. Our results and those in the literature show that brain nuclear T3 receptor and angiotensinogen mRNA levels and 5'D-II activity are dependent upon normal thyroid hormone concentrations. Several subfractions of cell signalling proteins (G protein alpha subunits) are compromised in hypo- and hyperthyroidism and the activities of protein kinases A and C are up-regulated in the hypothyroid state in a brain region-specific manner. The activities of acid phosphatase and aryl sulphatase A are compromised in the brain of hypothyroid rats, indicating a degree of lysosomal dysfunction, and several neurotransmitter metabolic enzymes and receptor systems are also affected. Metabolic experiments indicate that glutamate and acetate metabolism are compromised in the hypothyroid state, although glucose metabolism remains normal. Primary cultures of confluent neurons and astrocytes also strongly indicate a critical role for thyroid hormones in the control of amino acid uptake, protein synthesis, glycoprotein synthesis and 2-deoxyglucose uptake, in a cell-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Changes in brain functional connectivity in Alzheimer-type and multi-infarct dementia.

Clinical and neuropathological evaluation of elderly subjects with dementia has traditionally concentrated upon the focal distribution of brain disease, ignoring changes in the complex connections that link brain areas and that are crucial for cognition. We examined subjects with the two most common forms of dementia in the elderly (dementia of the Alzheimer type or DAT, and multi-infarct dementia or MID); and used electroencephalographic (EEG) coherence to examine the effects of these illnesses on the functional connections between brain areas. We studied coherence between brain areas known to be linked by two different types of connections: (i) dense narrow bands of long corticocortical fibres; (ii) broad complex networks of corticocortical and corticosubcortical fibres. Areas that were linked by dense narrow bands of long corticocortical fibres showed greatly diminished coherence in subjects with DAT; among MID subjects, this coherence was not significantly affected. Areas that were linked by broad connective networks showed the largest decreases in coherence among MID subjects. These findings are consistent with neuropathological evidence that Alzheimer's disease is a neocortical 'disconnection syndrome' in which there is a loss of structural and functional integrity of long corticocortical tracts. The findings further suggest that the vascular disease of MID most prominently affects broad fibre networks that may be more vulnerable to diffuse subcortical vascular damage. A ratio of coherence from complex corticocortical-corticosubcortical networks divided by coherence from long corticocortical tracts correctly classified 76% of subjects into DAT and MID categories. Overall, these results indicate that EEG coherence detects basic pathophysiological differences between subjects with DAT and MID, and that these differences may be clinically useful.

Aged↗
PubMed2000

Magnetic resonance studies of brain function and neurochemistry.

In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.

Animals↗
PubMed1999

Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites.

The synthesis of NAD (or NADP) from tryptophan involves a series of enzymes and the formation of a number of intermediates which are collectively called 'kynurenines.' In the late 1970s and early 1980s, it became clear that intraventricular administration of several 'kynurenines' could cause convulsions and that one of the 'kynurenines,' quinolinic acid, was an agonist of a sub-population of NMDA receptors and caused excitotoxic neuronal death. A related metabolite, kynurenic acid, could, on the other hand, reduce excitotoxin-induced neuronal death by antagonising ionotropic glutamate receptors. Since then, modifications in quinolinic and kynurenic acid synthesis have been proposed as a pathogenetic mechanism in Huntington's chorea and epilepsy. It was subsequently shown that a robust activation of the kynurenine pathway and a large accumulation of quinolinic acid in the central nervous system occurred in several inflammatory neurological disorders. More recently, it has been shown that 3OH-kynurenine or 3OH-anthranilic acid, two other kynurenine metabolites, may cause either apoptotic or necrotic neuronal death in cultures and that inhibitors of kynurenine hydroxylase may reduce neuronal death in in vitro and in vivo models of brain ischaemia or excitotoxicity. Finally, it has been reported that indole metabolites, indirectly linked to the kynurenine pathway, are able to modify neuronal function and animal behaviour by interacting with voltage-dependent Na+ channels. Oxindole, one of these metabolites, has sedative and anticonvulsant properties and accumulates in the blood and brain when liver function is impaired. In conclusion, a number of metabolites affecting brain function originate from tryptophan metabolism. Selective inhibitors of their forming enzymes may be useful to understand their role in physiology or as therapeutic agents in pathology.

Animals↗