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Prediction of long-term outcome in high-risk infants: the use of objective measures of brain structure and function in the neonatal intensive care unit.

The ability to predict long-term outcome on the basis of objective measures made shortly after the birth of an infant has introduced a completely new approach to the investigation of the aetiology of childhood impairments and disabilities, and the evaluation of the effects of perinatal management regimes designed to avoid or ameliorate them. This approach also has important implications for the management of sick and vulnerable infants, both in the perinatal period and later. From the use of ultrasound brain scanning, a great deal has been learnt about all aspects of the aetiology, evolution and prognosis of GLH, IVH and IPH in very preterm infants; and from autopsy correlation studies, about the underlying pathological processes causing the lesions. There are, however, three observations which have particular implications for the choice of neonatal measure to be used for predictive purposes and for the interpretation of results. First, the long-term prognosis for infants with uncomplicated GLH and IVH who never develop ventricular dilatation, hydrocephalus or evidence of loss of brain tissue is indistinguishable from that of very preterm infants of similar gestational age with no detectable lesions on the ultrasound scan. Second, hypoxic-ischaemic injury is a much more common cause of the neurodevelopmental impairments seen at follow-up in sick or preterm infants than haemorrhage. Third, ultrasound is very poor at detecting hypoxic-ischaemic lesions in the absence of bleeding. These lesions are only reliably recognized with ultrasound when the necrotic process is sufficiently advanced for loss of brain tissue or cerebral atrophy to occur. As a consequence, hypoxic-ischaemic injury is only likely to be identified in the early stages of its evolution following the causal insult by demonstrating deranged cerebral intracellular energy metabolism or cerebral haemodynamics. From these observations it may be deduced that ultrasound brain scanning in the first week of life is a poor predictor of adverse neurodevelopmental outcome at follow-up, depending largely on the diagnosis of haemorrhagic lesions for its 'power'. According to the size of haemorrhage and the outcome considered, the sensitivity may be calculated at 61-73.5% and the positive predictive value at only 32-50% (Stewart ef al, 1987; Cooke, 1987). Nevertheless, the marked echodensities which indicate intraparenchymal haemorrhage (IPH or haemorrhagic PVL) carry a very bad prognosis and thus detect a small group of infants with a probability estimate of serious neurodevelopmental impairment of about 90% (Table 1).(ABSTRACT TRUNCATED AT 400 WORDS)

Asphyxia Neonatorum↗

[The delayed effects of systemic circulatory arrest on the free-radical processes in the brain structures of rats with different types of behavior in the emotional resonance test].

Male Wistar rats with different types of behavior in "emotional resonance" test ("active" and "passive") were studied one week after the global ischemia induced by cardiac arrest. Recovery of some physiological functions as well as free-radical-mediated processes and NO-synthase activity were studied in cerebral structures and blood serum. The "open-field" behavior normalized more rapidly in the "active" rats than in the "passive" ones, though the time course of the neurologic deficit compensation did not differ in these groups. A decrease in superoxide scavenging activity and in the content of 2-thiobarbituric acid-reactive material was revealed in the cerebral structures of both "active" and "passive" rats. Increased levels of free-radical generation in the hippocampus of the "passive" rats and in the cerebellum of the "active" rats were found. Higher NO-synthase activity was demonstrated in the cerebellum of the "passive" rats. Taken together, these data suggest that there are specific patterns of free-radical-mediated processes in the brain of rats with different types of behavior in "emotional resonance" test.

Analysis of Variance↗

The relationship of structural brain imaging parameters to antipsychotic treatment response: a review.

Over the last decade, a number of studies have attempted to relate brain morphology to treatment response to neuroleptics. This approach has scientific potential to define subtypes of schizophrenia as well as potential clinical utility. In the present report, a review of 33 studies, including a meta-analysis, is provided. Although the overall test of the effect was not significant, the analysis revealed marked heterogeneity in the results of the various studies. The following factors were significant predictors of effect size: age, illness duration and age of onset of the patient cohort, the percentage of patients with marked structural abnormality included in the study overall, the duration of treatment and the degree of symptom improvement in the study overall. The following factors were unrelated to study effect size: date of study, gender, and the presence of a washout period. In future studies, attention to the parameters utilized in the meta-analysis should help to clarify the strength and generality of the relationship between brain morphology and treatment response.

Adult↗

Transforming growth factor-alpha induces sex-specific neurochemical imbalance in the stress- and memory-associated brain structures.

Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes. However, its role in adult nervous system is yet unclear. Studies have shown that TGFalpha can regulate stress and memory behavior in adult mice. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, the stress response and memory are impaired predominantly in males and only after puberty. To determine the neurochemical changes resulting from the reduced TGFalpha levels that could explain the reported behavioral outcomes, biogenic amine and amino acid levels were determined in the brain regions associated with stress and memory. Interestingly, sex-specific alterations in neurochemical levels were detected, including elevated noradrenaline and reduced glutamate levels in striatum of Wa-1 males, increased noradrenaline and reduced serotonin metabolite levels in hippocampus of Wa-1 females, reduced serotonin metabolite levels in cortex and amygdala of Wa-1 females, and reduced noradrenaline, dopamine, serotonin, glutamate and glycine levels in hypothalamus of Wa-1 females compared to their respective controls. Increased dopamine turnover in cortex and reduced dopamine and serotonin turnover in amygdala were observed in both male and female Wa-1 mice. The data indicate sex-specific alterations of specific neurochemicals as a result of reduced TGFalpha expression, which may underlie sex-dependent stress response and memory impairment in Wa-1 mice.

Animals↗

[The effect of hippocampal stimulation on the evoked electrical activity of different brain structures].

The functional relationships of the dorsal and ventral hippocampus and entorhinal area were studied in cats. The dorsal hippocampus was shown to suppress the electric activity and evoked responses to entorhinal stimulation in the ventral hippocampus and other structures. The dorsal hippocampus inhibits evoked responses to skin stimulation in entorhinal area and ventral hippocampus. The ventral hippocampus produced opposite effects. The functional differences of the dorsal and ventral hippocampus suggest different connections with entorhinal area.

Animals↗

[The role of glucocorticoids in the post-vibration changes in inhibition mediation in the brain structures].

Low-frequency vertical vibration for 2 hours together with three-fold increase of glucocorticoids is accompanied by the disruption of typical relationships of neuromediator processes (norepinephrine- and serotoninergic mediation) as well as the reduction of the intensity of choline trapping with glucocorticoid perception. Glucocorticoid-related conformation changes in plasma membranes and a drastic increase of the cAMP level provide plasticity of both nonspecific (hypothalamus, raphe bluish sites and nuclei) and specific (Deiters' nuclei) structures. The relationships of neuromediator processes in different CNS structures depend on the content of glucocorticoids. This should be taken into consideration when developing pathogenetically adequate methods for restoring the vestibular component of the motion sickness syndrome.

Animals↗

Auditory-conditioned-fear-dependent c-Fos expression is altered in the emotion-related brain structures of Fyn-deficient mice.

Fyn-tyrosine-kinase-deficient mice exhibit increased fearfulness. To elucidate the neural mechanisms of their emotional defects, we compared fyn(-/-) and fyn(+/-) mice by behavioral analysis of conditioned fear and by functional neuroanatomical analysis of the distribution of highly responsive neurons associated with conditioned fear. The mice were exposed to the auditory conditioned stimulus paired with electric shock as the unconditioned stimulus. After the fear conditioning, auditory stimulus-induced freezing behavior was enhanced in fyn(-/-) mice. When the occurrence of c-Fos-immunoreactive neurons in the brain of fear-conditioned mice was examined following exposure to the auditory stimulus, a significant increase in immunoreactive neurons was found in the amygdala, hypothalamus, and midbrain of both genotypes. The occurrence of conditioned-fear-dependent c-Fos-immunoreactive neurons was enhanced in the central, medial, cortical, and basomedial amygdaloid subdivisions, the hypothalamic nuclei, and the midbrain periaqueductal gray of the fyn(-/-) mice in comparison with the fyn(+/-) mice. However, remarkably, the occurrence of conditioned-fear-dependent c-Fos-immunoreactive neurons was very low in the basolateral and lateral amygdaloid subdivisions of the fyn(-/-) mice, in striking contrast to a significant increase in c-Fos-immunoreactive neurons in these subdivisions in the fyn(+/-) mice. These findings suggest that the increased excitability of the specific amygdaloid subdivisions including the central nucleus, and of the projection targets such as the hypothalamus and midbrain in fyn(-/-) mice, is directly related to the enhanced fear response, and that the decreased excitability in the basolateral and lateral amygdaloid subdivisions is involved in the defective control of the neural circuit for emotional expression in this mutant.

Acoustic Stimulation↗

Classification of sulpiride, clozapine and haloperidol by toposelective recording from different brain structures in the immobilized rat (stereo-EEG).

The formerly designed method for quantitative evaluation of drug effects in rats is employed for the classification of three different neuroleptic drugs, namely sulpiride, clozapine and haloperidol. Analysis of the power density spectra as obtained from the recorded activity in the cortex, striatum and reticular core results in a 'fingerprint' for each drug, which is then compared to the known data on various standard drugs by means of a stepwise discriminant analysis. After cumulative dosage dose-response curves are given for single frequency bands and different brain areas. The ED50 values are close to the drug dosages applied to humans. All three neuroleptics can be differentiated from each other, but are classified very close to low dosages of chlorpromazine according to the classification rule established in an earlier paper. Relying on the overall difference of the drug's action in comparison to placebo, a single dose-response relationship is given for each compound.

Animals↗

[The modelling of the modes of propagation of SD waves in brain structures taking into account the nonuniform density of the active elements].

Character of spreading depression (SD) wave propagation was studied on two-dimensional model of excitable tissue. It was shown that strips with diminished density of active elements were of different permeability for the waves depending on their front orientation and curvature. When triggered near the border with a rarefied strip the wave could not penetrate through it and the effect of wave "sliding" along this strip was observed. In several-compartment model imitating the diffusely connected cortico-striatal system of the rat brain the sequence of events was determined by a primary focus position. In this model a single stimulus could provoke not only one wave but re-entry waves and reverberators. Described mechanism of repetitive waves generation in inhomogeneous tissue allow to interpret unusual SD wave consequences observed in electrophysiological experiments.

Animals↗

Studies on brain structure and neurological function in alcoholic rats controlled by an Indian medicinal formula (SKV).

An Indian herbal brew known in Ayurvedic pharmacy as asavam (SKV) was tested for its effectiveness in controlling addiction to ethanol in rats. Rats on SKV therapy with free access to 15% ethanol showed a marked reduction in voluntary ethanol intake. Their performance in simple neurological tests improved and a reversal of ethanol-induced changes in the electroencephalogram and electrocardiogram were also recorded. SKV treatment appeared to correct the fatty changes in liver and the signs of haemorrhage, demyelination and spongiosis seen in the brain of ethanol-fed rats.

Alcoholism↗

[Aldehyde dehydrogenase activity in the barrier brain structures].

The histochemical method was used to study the aldehyde dehydrogenase (EC 1.2.1.3.; ALDH) activity in capillaries and glial structures of different regions in the rat central nervous system (CNS). The occurrence of three metabolic barriers for aldehydes on systemic level in the CNS has been shown. They are: the barrier between blood and the nervous tissue (represented by capillary endothelium and surrounding astrocytes ALDH), that between blood and cerebrospinal fluid (ALDH in ependymocytes of vascular plexus), and that between cerebrospinal fluid and nervous tissue (ALDH of ependymocytes covering brain cavities). On the single microregions level a similar barrier is between interstitial fluid and neurons (ALDH of satellite oligodendrocytes).

Aldehyde Dehydrogenase↗

[Prenatal developmental disorders of brain structures in schizophrenic psychoses].

In recent years neuroimaging techniques have revealed various cerebral and structural variances in patients with schizophrenic psychoses. The best established findings are the enlargement of the lateral ventricles and discrete structural deficits in temporobasal structures of the cortex. Neuropathological investigations have detected subcortical as well as cortical variances. Subcortically, the volume of the striatum and the globus pallidus have been found to be enlarged in schizophrenics. Among the cortical deviations, the cytoarchitectonic disturbances of the rostral entorhinal region have been well documented and are especially important. According to neuropathological criteria, they are derived from disturbances of prenatal cell migration within the central nervous system. Due to its close anatomical and functional connection with the hippocampal formation and its being the assembly point of all sensory cortical areas, disturbances of this area could seriously impede the processing and filtering of information within the limbic system. The other hitherto reported structural anomalies, such as the disturbance to the radial order of hippocampal neurons, and the abnormal structures in the frontobasal orbital regions and the rostroventral insula, could be connected to the disturbances of migration within the entorhinal region; the former could be secondary, but still prenatal developments. Well documented are the architectonic changes in the rostral cingulate gyrus which is itself connected with the entorhinal region via the Papez circuit. These findings are supported and supplemented by the results of epidemiological studies which indicate a disturbance of brain development during the second trimenon of the prenatal period. Viral infections (Influenza A2) of mothers during this critical period appear to play an especially important role.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Imaging brain structure and function, infection and gene expression in the body using light.

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted-light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain functions in adults. The generated-light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real-time, non-invasive monitoring and imaging of infection and gene expression in vivo using low-light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.

Adult↗

Structural brain mutant of Drosophila melanogaster with reduced cell number in the medulla cortex and with normal optomotor yaw response.

KS58, one out of six known alleles of the small optic lobes (sol) gene in Drosophila melanogaster, reduces the cell number in the medulla cortex by degeneration of ganglion cells in the pupae to about 50%. Also, about half the volume of the medulla and lobula complex neuropils is missing. Many Golgistained cells in the mutant optic lobes resemble their homologues in wild type. However, special classes of transmedullary columnar neurons projecting to the lobula or to both lobula and lobula plate are not seen in the mutant. Some neurons linking the lobula complex to the central brain send branches to the medulla (the branches do not exist in wild type); some other types seem to be missing. The fate mapping of the KS58 focus reveals a location ventral to the head bristles and in sine oculis (so) flies the mutation further reduces the rudiments of the optic lobes normally seen. Therefore the sol phenotype is not induced by mutant eyes and the primary gene action seems to be on nervous tissue. The structural alterations of the small optic lobes are reflected in visual orientation behavior. The optomotor yaw response, however, is almost quantitatively preserved. The respective neural network should still be present in the mutant optic lobes.

Journal Article↗

Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice.

Previous studies have established that abrogation of monoamine oxidase (MAO) A expression leads to a neurochemical, morphological, and behavioral specific phenotype with increased levels of serotonin (5-HT), norepinephrine, and dopamine, loss of barrel field structure in mouse somatosensory cortex, and an association with increased aggression in adults. Forebrain-specific MAO A transgenic mice were generated from MAO A knock-out (KO) mice by using the promoter of calcium-dependent kinase IIalpha (CaMKIIalpha). The presence of human MAO A transgene and its expression were verified by PCR of genomic DNA and reverse transcription-PCR of mRNA and Western blot, respectively. Significant MAO A catalytic activity, autoradiographic labeling of 5-HT, and immunocytochemistry of MAO A were found in the frontal cortex, striatum, and hippocampus but not in the cerebellum of the forebrain transgenic mice. Also, compared with MAO A KO mice, lower levels of 5-HT, norepinephrine, and DA and higher levels of MAO A metabolite 5-hydroxyindoleacetic acid were found in the forebrain regions but not in the cerebellum of the transgenic mice. These results suggest that MAO A is specifically expressed in the forebrain regions of transgenic mice. This forebrain-specific differential expression resulted in abrogation of the aggressive phenotype. Furthermore, the disorganization of the somatosensory cortex barrel field structure associated with MAO A KO mice was restored and became morphologically similar to wild type. Thus, the lack of MAO A in the forebrain of MAO A KO mice may underlie their phenotypes.

Animals↗

[Receptor binding of corticosterone in brain structures participating in regulation of the hypothalamo-hypophyseo-adrenal system].

Binding of corticosterone by the cytosol receptors after hydrocortisone administration was studied in different tissues of rats. A decrease in the specific binding of corticosterone occurred within 24 hrs in all the structures under study. In 3 days the decrease only persisted in the hypophysis and hypothalamus. The data suggest a connection between the long lasting decrease in the cytosol reception of corticosterone in the hypothalamus and hypophysis and the blockade of the hypothalamo-hypophyseal-adrenal system.

18-Hydroxycorticosterone↗