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Investigating dynamic aspects of brain function in slice preparations: spatiotemporal stimulus patterns generated with an easy-to-build multi-electrode array.

Electrical stimulation of nervous tissue with single stimulating electrodes is a technique widely used for the investigation of nervous system function. While it has proved to be useful in all kinds of experiments, single electrode stimuli are, however, far from being 'natural'. In most parts of the living brain, incoming activity results from the firing of a large number of presynaptic neurons, thus reflecting a complex combination of space and time aspects of neural activity. In this paper, a multi-electrode stimulating system is introduced which allows for the generation of fast space-time stimulus patterns. An example for the application of dynamic input patterns to the cerebellar cortex in vitro is given. The corresponding experiments revealed aspects of cerebellar function which cannot be seen using static or single electrode stimulation.

Animals↗

Recovery of brain function following ischemia.

Experimental evidence conveys clear suggestions that early reperfusion following at least focal cerebral ischemia in the primate is accompanied by a return of function demonstrably suspended during the ischemic period. Complete and permanent arrest of the cerebral circulation has been known within seconds to lead to depression of brain electrical activity, and within minutes to gross disruption of the normal energy metabolism with failure of ionic homeostatic mechanisms. There is irreversible cell change and death within 5 to 10 minutes. Very much more protracted periods of ischemia have been shown more recently to be associated with potential viability of neuronal function, and in clinical neurosurgery we have known for years that patients with established cerebral vascular occlusion and a dense neurological deficit may show quite evident improvement over months or years. In these protracted recoveries, the potential for re-learning in nervous circuits may play a part, but in more acute circumstances, for example in the progressive recovery from vasospasm, re-learning is clearly not a factor, and this demonstrates quite evidently that neurons at one moment apparently non-functioning, can again within a few minutes recover function even after hours of apparent suppression. The experimental evidence is fairly well known. In this symposium and elsewhere we have presented a model of experimental occlusion of the middle cerebral artery in primates demonstrating irreversible recovery of electrical function after some 20 minutes of middle cerebral artery occlusion, and reversible recovery of ionic homeostasis after periods of up to an hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Frontal, temporal and lateralized brain function in children with attention-deficit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on development.

This article considers deficits in the selective aspects of perception underlying symptoms of impaired attention and impulsivity in children with attention-deficit hyperactivity syndrome (ADHD) in terms of frontal and temporal lobe function and cerebral asymmetry. Tomographic studies suggest a disturbed fronto-striatal function, but have neglected limbic contributions under activating conditions and are equivocal on the nature of apparent lateralized differences. Neuropsychological and psychophysiological studies suggest that early and late stages of information processing are affected in both the frontal and temporal lobes and imply impaired intercortical dialog. Given the evidence for a normal specialization in global processing in the right and the processing of details in the left hemisphere, the lateralized impairment may progress from situational ADHD (impaired selective aspects of perception on the right) to pervasive ADHD (additional impairment in decision-making on the left). Accordingly some ADHD children may experience an early negative neurodevelopmental influence that only appears as the brain region matures while others show a delayed development of CNS function.

Attention Deficit Disorder with Hyperactivity↗

Determination of creatine kinase kinetic parameters in rat brain by NMR magnetization transfer. Correlation with brain function.

The pseudo first-order rate constant kf of the creatine kinase (CK) forward reaction as well as the CK forward flux FCK,f have been shown to correlate better with cardiac performance than the steady-state levels of ATP and PCr (Bittl, J. A., and Ingwall, J. S. (1985) J. Biol. Chem. 260, 3512-3517). In order to elucidate the relationship between the CK kinetic parameters and brain activity, we have determined, using the non-invasive NMR technique of magnetization transfer, kf and FCK,f in rats, in which brain activity was experimentally varied by administration of either thiopental sodium or bicuculline to decrease or increase electro-encephalogram (EEG) intensity, respectively. The steady-state levels of ATP and PCr, as well as the accumulation of deoxyglucose 6-phosphate (DG-6P) in brain following intraperitoneal administration of deoxyglucose, were determined simultaneously by the NMR technique, whereas the cortical EEG was recorded in a separate experiment. The EEG intensity (range, 1-20 Hz), taken as a measure for brain performance, as well as the amount of DG-6P formed in brain, reflecting the synthesis rate of high energy phosphates (ATP and PCr), linearly correlated with kf. Despite large changes in both EEG intensity (50-250%) and kf (0.12-0.69 s-1) between thiopental sodium- and bicuculline-treated rats, the ATP levels remained constant, whereas the PCr levels decreased with high EEG activity. In contrast to the expectation based on model calculations of CK kinetics, the PCr levels did not increase above control values at reduced EEG intensity (50% of controls). At EEG intensities exceeding control values (bicuculline-treated rats) FCK,f increased as predicted by CK equilibrium. In conclusion, we have shown that in the rat brain, like in the heart, the CK forward rate constant kf, in contrast to ATP and PCr levels, is a sensitive reliable indicator of both increased and reduced function.

Adenosine Triphosphate↗

An orphan seven-transmembrane domain receptor expressed widely in the brain functions as a coreceptor for human immunodeficiency virus type 1 and simian immunodeficiency virus.

Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV) strains use CCR5 as a coreceptor, and many SIV strains can use CCR5 independently of CD4. In addition, several orphan seven-transmembrane receptors which can serve as HIV-1 and SIV coreceptors have been identified. Here we report that APJ, an orphan seven-transmembrane domain receptor with homology to the angiotensin receptor family, functions as a coreceptor for a number of HIV-1 and SIV strains. APJ was expressed widely in the human brain and in NT2N neurons. APJ transcripts were also detected by reverse transcription-PCR in the CD4-positive T-cell line C8166, but not in peripheral blood leukocytes, microglia, phytohemagglutinin (PHA)- or PHA/interleukin-2-stimulated peripheral blood mononuclear cells, monocytes, or monocyte-derived macrophages. The widespread distribution of APJ in the central nervous system coupled with its use as a coreceptor by some HIV-1 strains indicates that it may play a role in neuropathogenesis.

Animals↗

MR spectroscopy: a powerful tool for investigating brain function and neurological diseases.

Magnetic resonance spectroscopy (MRS) has attracted much attention in recent years and has become an important tool to study in vivo particular biochemical aspects of brain disorders. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, investigation by in vivo 1H MRS provides chemical information on tissue metabolites, thus enabling a non-invasive assessment of changes in brain metabolism underlying several brain diseases. In this review a brief description of the basic principles of MRS is given. Moreover, we provide some explanations on the techniques and technical problems related to the use of 1H MRS in vivo including water suppression, localization, editing, quantitation and interpretation of 1H spectra. Finally, we discuss the more recent advancement in three major areas of neurological diseases: brain tumors, multiple sclerosis, and inborn errors of metabolism.

Brain↗

Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo.

We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.

Animals↗

[Brain functional status in patients suffering from hemorrhagic fever with renal syndrome].

EEG mathematical analysis in 59 patients with hemorrhage fever with renal syndrome (HFRS) revealed significant changes of bioelectrical brain activity, being expressed most distinctly during severe course, in the different stages of the disease. Re-convalescents after HFRS severe type showed lower EEG coherence indices in all frequency bands that argued for consistency of electric process dysfunctions in great brain cortex and might reflect structural brain damage. The data obtained exhibit higher informative ness of the EEG mathematical analysis not only in the context of differential and diagnostic perspectives but also for adequate evaluation of cerebral disturbance expression and their manifestation prognosis in the HFRS patients.

Acute Disease↗

Kappa opiate receptor agonists: effects on behavior and on brain function and structure in rhesus monkeys.

In the present study several drugs that are predominantly agonists of kappa receptors were tested in rhesus monkeys prepared with deep and surface brain electrodes. The administration of two benzomorphan derivatives and of ethylketocyclazocine induced acute behavioral effects resembling catatonia concomitant with generalized spike and slow-wave electroencephalographic activity at widespread brain sites, that lasted for about 1 hr. After administration of one to three doses of these agonists (the benzomorphan derivatives to five monkeys and the ethylketocyclazocine to two monkeys), chronic recording changes developed, characterized by continuous high-amplitude spiking activity focal at the anterior septal region and periaqueductal gray of the mesencephalon. They increased in intensity with the passage of time, the monkeys having been followed as long as 5 months without further drug administration. Light microscopy and electron microscopy showed no structural abnormalities in the monkey brains at the sites of altered recordings, although occasional dendritic atrophy was noted at all cortical and subcortical brain sites examined. Chronic recording changes did not develop in a monkey that received U-50,488H on eight occasions. And none of the electrode-implanted monkeys that served as controls (having received no kappa agonists) developed recording changes. The sites affected by the active kappa agonists were those at which abnormal activity has been correlated with psychotic behavior. The ability of the kappa agonists to induce a lasting physiologic change without corresponding structural change at those focal sites implicated in schizophrenia may prove a useful probe in further investigations into the cause of schizophrenia and its ultimate treatment.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗