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PubMed2001

Secretory ribonucleases in the primitive ruminant chevrotain (Tragulus javanicus).

Phylogenetic analyses of secretory ribonucleases or RNases 1 have shown that gene duplication events, giving rise to three paralogous genes (pancreatic, seminal and brain RNase), occurred during the evolution of ancestral ruminants. A higher number of paralogous sequences are present in chevrotain (Tragulus javanicus), the earliest diverged taxon within the ruminants. Two pancreatic RNase sequences were identified, one encoding the pancreatic enzyme, the other encoding a pseudogene. The identity of the pancreatic enzyme was confirmed by isolation of the protein and N-terminal sequence analysis. It is the most acidic pancreatic ribonuclease identified so far. Formation of the mature enzyme requires cleavage by signal peptidase of a peptide bond between two glutamic acid residues. The seminal-type RNase gene shows features of a pseudogene, like orthologous genes in other ruminants investigated with the exception of the bovine species. The brain-type RNase gene of chevrotain is expressed in brain tissue. A hybrid gene with a pancreatic-type N-terminal and a brain-type C-terminal sequence has been identified but nothing is known about its expression. Phylogenetic analysis of RNase 1 sequences of six ruminant, three other artiodactyl and two whale species support previous findings that two gene duplications occurred in a ruminant ancestor. Three distinct groups of pancreatic, seminal-type and brain-type RNases have been identified and within each group the chevrotain sequence it the first to diverge. In taxa with duplications of the RNase gene (ruminants and camels) the gene evolved at twice as fast than in taxa in which only one gene could be demonstrated; in ruminants there was an approximately fourfold increase directly after the duplications and then a slowing in evolutionary rate.

Animals↗

PubMed1999

Evolution of functional reorganization in hemiplegic stroke: a serial positron emission tomographic activation study.

We used serial positron emission tomography (PET) to study the evolution of functional brain activity within 12 weeks after a first subcortical stroke. Six hemiplegic stroke patients and three normal subjects were scanned twice (PET 1 and PET 2) by using passive elbow movements as an activation paradigm. Increases of regional cerebral blood flow comparing passive movements and rest and differences of regional cerebral blood flow between PET 1 and PET 2 in patients and normal subjects were assessed by using statistical parametric mapping. In controls, activation was found in the contralateral sensorimotor cortex, supplementary motor area, and bilaterally in the inferior parietal cortex with no differences between PET 1 and PET 2. In stroke patients, at PET 1, activation was observed in the bilateral inferior parietal cortex, contralateral sensorimotor cortex, and ipsilateral dorsolateral prefrontal cortex, supplementary motor area, and cingulate cortex. At PET 2, significant increases of regional cerebral blood flow were found in the contralateral sensorimotor cortex and bilateral inferior parietal cortex. A region that was activated at PET 2 only was found in the ipsilateral premotor area. Recovery from hemiplegia is accompanied by changes of brain activation in sensory and motor systems. These alterations of cerebral activity may be critical for the restoration of motor function.

Aged↗

PubMed1995

Central pontine myelinolysis as a complication of partial ornithine carbamoyl transferase deficiency.

Central pontine myelinolysis (CPM) is a demyelinating condition of the central pons with or without associated foci of demyelination in extrapontine areas. We present a case of partial ornithine carbamoyl transferase deficiency in a 5-year-old girl which was complicated by CPM. The patient was a previously undiagnosed girl who presented with mild hyperammonemic encephalopathy with a maximum plasma ammonia level of 376 microM on admission. Laboratory testing established the diagnosis of OCT deficiency, and therapy with hydration and protein restriction was successful in returning the plasma ammonia levels to normal. Five days after correction of her hyperammonemia, the patient developed intractable seizures and coma. Serial MRI scans of the brain revealed the evolution of the characteristic findings of CPM. Plasma ammonia and electrolyte concentrations were well controlled throughout this time. This represents the first description of CPM in a patient with a urea cycle defect.

Amino Acid Metabolism, Inborn Errors↗

PubMed2002

Distribution of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivity in the central nervous system of two chondrostean fishes (Acipenser baeri and Huso huso).

To obtain a better understanding of the evolution of the brain catecholaminergic systems of fishes, we have examined the distribution of catecholamine-synthesizing enzymes in two species of sturgeon (Acipenser baeri and Huso huso) using antibodies against tyrosine hydroxylase (TH) and dopamine-beta -hydroxylase (DBH; only analyzed in Acipenser). Both sturgeons showed TH-immunoreactive (THir) neurons widely distributed in most regions of the brain, the highest number of THir cells being located in the forebrain (olfactory bulb, preoptic area, and posterior tuberculum). THir cells were also seen in other forebrain areas (retrobulbar area, dorsal and ventral telencephalic areas, hypothalamus, ventral thalamus, pretectal area) and in the brainstem (locus coeruleus, viscerosensory area, caudal reticular formation, and area postrema). Immunoreactive fibers and varicosities showed a wide distribution, being particularly abundant in the diencephalon and mesencephalon. DBH-immunoreactive (DBHir) cells were observed in the anterior tuberal nucleus, where these cells were TH-negative, and in the locus coeruleus and the caudal rhombencephalon (vagal reticular formation), where the DBHir cells were also THir. DBHir fibers were scarce in the telencephalon and very abundant in the diencephalon, mesencephalon, and rhombencephalon. The comparative analysis of the catecholaminergic systems of chondrosteans and those observed in other groups of fishes and tetrapods indicate a similar organization of many nuclei, as well as characteristics that are probably primitive, such as the presence of a large number of forebrain catecholaminergic groups.

Animals↗

PubMed2001

Diffusion-weighted magnetic resonance imaging detects early neuropathology following four vessel occlusion ischemia in the rat.

Early neuropathology following a prolonged duration of four-vessel occlusion (4 VO) ischemia in the rat was charted using magnetic resonance imaging (MRI). Animals received either 30 minutes of 4 VO (N = 6) or sham operation (N = 6) prior to in vivo assessment. Proton density and T(2) and combined T(2)/diffusion-weighted (T(2)/DW) MRI were performed at 6, 24, and 72 hours postocclusion. T(2)/DW imaging was the most effective sequence for delineating between injured and intact tissues, indicating neuropathology in the dorsolateral striatum at 24 hours and in the CA1/CA2 subfields of the hippocampus at 72 hours following ischemia. Apparent diffusion coefficient values were significantly reduced in the striatum (P = 0.03) and hippocampus (P = 0.005) at 24 and 72 hours, respectively. This is the first report, to our knowledge, of T(2)/DW imaging detecting lesions following 4 VO in accord with the known temporal evolution of ischemic brain damage.

Animals↗

PubMed1997

Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat.

Breakdown of the cytoskeleton has been proposed to be a central event in the evolution of ischaemic brain damage. Alterations in the immunostaining of cytoskeletal proteins, particularly microtubule-associated protein (MAP) 2, have been suggested to be sensitive markers of ischaemic damage in the somatodendritic compartment. However, axons are also subjected to the adverse conditions created by an ischaemic challenge, but MAP2 is not located in the axonal compartment. The purpose of the present study was to examine immunostaining of beta-tubulin, MAP1a and MAP5, all of which are located in axons as well as perikarya, specifically in myelinated fibre tracts in rats subjected to unilateral middle cerebral artery (MCA) occlusion. In sham-operated control rats immunostaining of all three antibodies in myelinated fibre tracts had a smooth, regular appearance. Two hours after MCA occlusion there were striking changes in the patterns of immunostaining of all three antibodies in myelinated fibre tracts within the MCA territory. These were particularly noticeable in beta-tubulin- and MAP5-stained sections where the pattern in white matter had a rough, globular appearance. This pattern was accentuated at 6 h after MCA occlusion and the presence of "bulb-like" profiles in white matter tracts was notable particularly in the MAP5-stained sections. Thus, the changes in the patterns of staining at 2 h after MCA occlusion may represent the early stages of axonal disconnection, and immunostaining of microtubular proteins may represent a sensitive method to assess ischaemically induced damage to myelinated fibre tracts.

Animals↗

PubMed1995

Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study.

Breakdown of the cytoskeleton may be involved in the evolution of ischaemic brain damage and alterations in microtubule-associated proteins may play an important role in this process. In the present study, tau, a microtubule-associated protein predominantly located in axons, was examined after 2 or 6 h of focal cerebral ischaemia in the rat. Immunohistochemistry revealed increased Tau1 staining in the neuropil, some perikarya and in glial cells throughout the dorsolateral caudate nucleus and ventrolateral neocortex in the ipsilateral hemisphere at both 2 and 6 h after occlusion of the middle cerebral artery. Contrastingly, immunostaining of another tau antibody, TP70, was unchanged in the neuropil, but was increased specifically in glial cells in these regions. Immunoblotting revealed the presence of additional tau bands in tissue extracts of the caudate nucleus and ventrolateral neocortex ipsilateral to the occluded middle cerebral artery as detected by both tau antibodies after either 2 or 6 h. The results suggest that tau is dephosphorylated and/or degraded in axons and some neuronal perikarya in response to focal cerebral ischaemia. In contrast to the response in neurons, increased immunoreactivity of both tau antibodies in glial cells indicates a differential response of neuronal and glial tau to focal cerebral ischaemia.

Animals↗

PubMed1993

Sexual selection, Machiavellian intelligence, and the origins of psychosis.

According to Darwin's theory of sexual selection some features that differentiate the two sexes evolve by a process of "male competition" and "female choice". The sex difference in age of onset of psychotic illness in man may relate to a sexual dimorphism in cerebral organisation (the male brain being more lateralised or asymmetrical than the female brain), a difference consistent with a role for sexual selection in the evolution of the human brain. Differing criteria (reflected in a cross-culturally stable difference in mean age at marriage) in males and females for selecting personality characteristics in a mate may generate diversity in the balance of growth between the hemispheres, and this could maintain the high and relatively constant rates of psychosis in human populations.

Brain↗

PubMed1996

Self-organization in computer simulated selective systems.

In certain biologic systems, the signal selects functional or numerical expansion of the recognizing elements. Examples of these systems include the immune system, brain cortex, and evolution. One common feature of these Darwinian-type systems is degenerate recognition, in which one signal can recognize several different elements, with different affinities and consequences. For example, T cell antigen receptors and antibodies demonstrate relative but not absolute specificity of recognition. Thus, the variables of dose of the signal and affinity of the recognizing element modulate the outcome. Another feature of these systems is the ability to create self-organized patterns, which do not mirror the incoming signals. The hypothesis of this study is that degenerate recognition with subsequent selection of recognizing elements can explain self-organization of these systems. An entirely numerical model was explored, using the cellular automata approach. Three intrinsic features of a common selective system were incorporated into this model: a large number of recognizing elements; degenerative recognition of stimuli by these elements; and subsequent selection. Different numerical patterns of incoming stimuli were tested. The model showed self-organizing dynamics. Usually, the population of recognizing elements demonstrated an initial period of equilibrium, then a chaotic transitional state, and, finally, the bifurcational appearance of a stable self-organized pattern. The final resolution into a stable pattern can be either gradual or quasi-saltational. I conclude that systems with a large number of recognizing elements, degenerative recognition, and selection of recognizing elements can self organize based upon the pattern of the incoming stimuli.

Computer Simulation↗

PubMedDate not supplied

CBF and CBF/PCO2 reactivity in childhood strangulation.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2005

A new avian brain nomenclature: why, how and what.

Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of the avian brain have been based are in error, and consequently that terminology promotes misunderstanding of the functional organization of avian brain and its evolutionary relationship to mammalian brain. Recognizing this problem, a number of avian brain researchers began an effort to revise the terminology, which culminated in the Avian Brain Nomenclature Forum, held at Duke University from 18 to 20 July 2002. In the new terminology approved at this Forum, the flawed conception that the telencephalon of birds consists nearly entirely of a hypertrophied basal ganglia has been purged, and the actual parts of the basal ganglia and its brainstem afferent cell groups given names reflecting their now-evident mammalian homologues. The pallial telencephalic regions that were erroneously named to reflect presumed homology to mammalian basal ganglia were renamed as parts of pallium, using prefixes in most cases that retained established abbreviations (for continuity with the replaced nomenclature). The new nomenclature should lead to better communication among neuroscientists, especially between avian brain specialists and those not specialized in avian neurobiology. More information is available at the Avian Brain Nomenclature Exchange website ().

Animals↗

PubMed1998

Neuroimaging abnormalities in Indian patients with uncontrolled partial seizures.

In this series we performed clinical and imaging evaluation of 77 consecutive patients with uncontrolled partial seizures. Single cerebral parenchymal calcification (22 patients) was the most common imaging abnormality. Nine patients had multiple punctate calcifications. Other CT abnormalities included persistence of granulomatous lesion (enhancing) or multiple cystic lesions. In nine patients (of 22 patients with a normal CT scan) magnetic resonance imaging (MRI) was done, and two patients were seen to have circumscribed cystic lesions in the temporal lobes. The causes for uncontrolled seizures in India are totally different and revolve around neurocysticercosis, as the parasite sometimes runs a very long course of evolution in the brain. Sequelae of neurocysticercosis in the form of calcification is often a focus of epileptogenicity.

Adolescent↗

PubMed2003

Motor representation in patients rapidly recovering after stroke: a functional magnetic resonance imaging and transcranial magnetic stimulation study.

OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS). RESULTS: The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P<0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated. CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.

Adult↗

PubMed1993

Comparing communicative competence in child and chimp: the pragmatics of repetition.

Through an analysis of chimpanzee-human discourse, we show that two Pan troglodytes chimpanzees and two Pan paniscus chimpanzees (bonobos) exposed to a humanly devised symbol system use partial or complete repetition of others' symbols, as children do: they do not produce rote imitations, but instead use repetition to fulfil a variety of pragmatic functions in discourse. These functions include agreement, request, promise, excitement, and selection from alternatives. In so doing, the chimpanzees demonstrate contingent turn-taking and the use of simple devices for lexical cohesion. In short, they demonstrate conversational competence. Because of the presence of this conversational competence in three sibling species, chimpanzees, bonobos, and humans, it is concluded that the potential to express pragmatic functions through repetition was part of the evolutionary history of human language, present in our common ancestor before the phylogenetic divergence of hominids and chimpanzees. In the context of these similarities, two interesting differences appeared: (I) Human children sometimes used repetition to stimulate more talk in their conversational partner; the chimpanzees, in contrast, use repetition exclusively to forward the non-verbal action. This difference may illuminate a unique feature of human linguistic communication, or it may simply reflect a modality difference (visual symbols used by the chimpanzees, speech used by the children) in the symbol systems considered in this research. A second difference seems likely to reflect a true species difference: utterance length. The one- and two-symbol repetitions used by the chimpanzees to fulfil a variety of pragmatic functions were less than half the maximum length found in either the visual symbol combinations addressed to them by their adult human caregivers or the oral repetitions of two-year-old children. This species difference probably reflects the evolution of increased brain size and consequent increased memory capacity that has occurred since the phylogenetic divergence of hominids and chimpanzees four to seven million years ago.

Animal Communication↗

PubMed2000

Behaviourally driven gene expression reveals song nuclei in hummingbird brain.

Hummingbirds have developed a wealth of intriguing features, such as backwards flight, ultraviolet vision, extremely high metabolic rates, nocturnal hibernation, high brain-to-body size ratio and a remarkable species-specific diversity of vocalizations. Like humans, they have also developed the rare trait of vocal learning, this being the ability to acquire vocalizations through imitation rather than instinct. Here we show, using behaviourally driven gene expression in freely ranging tropical animals, that the forebrain of hummingbirds contains seven discrete structures that are active during singing, providing the first anatomical and functional demonstration of vocal nuclei in hummingbirds. These structures are strikingly similar to seven forebrain regions that are involved in vocal learning and production in songbirds and parrots--the only other avian orders known to be vocal learners. This similarity is surprising, as songbirds, parrots and hummingbirds are thought to have evolved vocal learning and associated brain structures independently, and it indicates that strong constraints may influence the evolution of forebrain vocal nuclei.

Animals↗

PubMed2006

Stability of discrete memory states to stochastic fluctuations in neuronal systems.

Noise can degrade memories by causing transitions from one memory state to another. For any biological memory system to be useful, the time scale of such noise-induced transitions must be much longer than the required duration for memory retention. Using biophysically-realistic modeling, we consider two types of memory in the brain: short-term memories maintained by reverberating neuronal activity for a few seconds, and long-term memories maintained by a molecular switch for years. Both systems require persistence of (neuronal or molecular) activity self-sustained by an autocatalytic process and, we argue, that both have limited memory lifetimes because of significant fluctuations. We will first discuss a strongly recurrent cortical network model endowed with feedback loops, for short-term memory. Fluctuations are due to highly irregular spike firing, a salient characteristic of cortical neurons. Then, we will analyze a model for long-term memory, based on an autophosphorylation mechanism of calcium/calmodulin-dependent protein kinase II (CaMKII) molecules. There, fluctuations arise from the fact that there are only a small number of CaMKII molecules at each postsynaptic density (putative synaptic memory unit). Our results are twofold. First, we demonstrate analytically and computationally the exponential dependence of stability on the number of neurons in a self-excitatory network, and on the number of CaMKII proteins in a molecular switch. Second, for each of the two systems, we implement graded memory consisting of a group of bistable switches. For the neuronal network we report interesting ramping temporal dynamics as a result of sequentially switching an increasing number of discrete, bistable, units. The general observation of an exponential increase in memory stability with the system size leads to a trade-off between the robustness of memories (which increases with the size of each bistable unit) and the total amount of information storage (which decreases with increasing unit size), which may be optimized in the brain through biological evolution.

Action Potentials↗

PubMed1998

Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia.

Focal cerebral ischemia is associated with expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), enzymes whose reaction products contribute to the evolution of ischemic brain injury. We tested the hypothesis that, after cerebral ischemia, nitric oxide (NO) produced by iNOS enhances COX-2 activity, thereby increasing the toxic potential of this enzyme. Cerebral ischemia was produced by middle cerebral artery occlusion in rats or mice. Twenty-four hours after ischemia in rats, iNOS-immunoreactive neutrophils were observed in close proximity (<20 micrometer) to COX-2-positive cells at the periphery of the infarct. In the olfactory bulb, only COX-2 positive cells were observed. Cerebral ischemia increased the concentration of the COX-2 reaction product prostaglandin E2 (PGE2) in the ischemic area and in the ipsilateral olfactory bulb. The iNOS inhibitor aminoguanidine reduced PGE2 concentration in the infarct, where both iNOS and COX-2 were expressed, but not in the olfactory bulb, where only COX-2 was expressed. Postischemic PGE2 accumulation was reduced significantly in iNOS null mice compared with wild-type controls (C57BL/6 or SV129). The data provide evidence that NO produced by iNOS influences COX-2 activity after focal cerebral ischemia. Pro-inflammatory prostanoids and reactive oxygen species produced by COX-2 may be a previously unrecognized factor by which NO contributes to ischemic brain injury. The pathogenic effect of the interaction between NO, or a derived specie, and COX-2 is likely to play a role also in other brain diseases associated with inflammation.

Animals↗

PubMed1991

Comparison of magnetoencephalography with other functional imaging techniques.

Recent advances in instrumentation and analysis in biomagnetism offer a unique tool for studying the spatiotemporal evolution of spontaneous brain activity as well as activity evoked by a stimulus. The overall performance characteristics of this and other techniques used to study the dynamics of brain function are compared. Particular emphasis is placed on defining the general spatiotemporal window of brain activity that each technique makes accessible. Similarities and differences associated with diverse modelling schemes for extracting source current density properties from electrographic recordings are stated.

Brain↗