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PubMed1998

Progressive brain failure after diffuse hypoxic ischemic brain injury: a serial MR and proton MR spectroscopic study.

The findings at sequential MR imaging and proton MR spectroscopy of a patient with profound hypoxic-ischemic brain injury are reported. The pattern of structural and biochemical changes observed closely reflected the known evolution of postasphyxic brain degeneration. Particularly noteworthy were the sharp decrease of cortical N-acetylaspartate in the acute phase, suggesting the severity of the neuronal insult, and the subsequent progressive increase of choline, paralleling the delayed degeneration of white matter.

Adult↗

PubMed2004

Surprisingly rapid growth in Neanderthals.

Life-history traits correlate closely with dental growth, so differences in dental growth within Homo can enable us to determine how somatic development has evolved and to identify developmental shifts that warrant species-level distinctions. Dental growth can be determined from the speed of enamel formation (or extension rate). We analysed the enamel extension rate in Homo antecessor (8 teeth analysed), Homo heidelbergensis (106), Homo neanderthalensis ('Neanderthals'; 146) and Upper Palaeolithic-Mesolithic Homo sapiens (100). Here we report that Upper Palaeolithic-Mesolithic H. sapiens shared an identical dental development pattern with modern humans, but that H. antecessor and H. heidelbergensis had shorter periods of dental growth. Surprisingly, Neanderthals were characterized by having the shortest period of dental growth. Because dental growth is an excellent indicator of somatic development, our results suggest that Neanderthals developed faster even than their immediate ancestor, H. heidelbergensis. Dental growth became longer and brain size increased from the Plio-Pleistocene in hominid evolution. Neanderthals, despite having a large brain, were characterized by a short period of development. This autapomorphy in growth is an evolutionary reversal, and points strongly to a specific distinction between H. sapiens and H. neanderthalensis.

Animals↗

PubMed2005

MeCP2 expression and function during brain development: implications for Rett syndrome's pathogenesis and clinical evolution.

Most cases of Rett syndrome (RTT) are associated with mutations of the transcriptional regulator MeCP2. On the basis of molecular structure, ontogeny, and subcellular and regional distribution, MeCP2 appears to be a link between synaptic activity and neuronal transcription. Integrating data on MeCP2 neurobiology, RTT neurobiology, MeCP2 mutational patterns in RTT and other disorders, histone profiles of relevance to RTT, and genotype-phenotype correlations in RTT, we update here our synaptic hypothesis of RTT. We postulate that MeCP2 dysfunction leads to abnormal brain development through maladjustment of neuronal gene expression to synaptic and other extra-cellular signals, mainly during the critical period of synaptic maturation. RTT phenotype will develop, only if severe MeCP2 dysfunction is present during early neuronal differentiation. Two models are proposed for explaining general and regional neuronal abnormalities in RTT and the phenotypical outcome of MeCP2 dysfunction, respectively.

Animals↗

PubMed1987

Effect of tetraploidy on dendritic branching in neurons and glial cells of the frog, Xenopus laevis.

Morphological aspects of four different groups of Golgi impregnated brain cells from a tetraploid strain of Xenopus laevis frogs were compared to analogous cells in comparably sized diploid frogs. The cells examined included neurons from the telencephalon, caudal hypothalamus, and optic tectum, and radial glial cells from the optic tectum. The brains of tetraploid frogs appeared grossly normal and were the same size and contained similar cell types as diploid brains. As observed in previous studies on polyploid amphibia, somal diameters increased significantly in tetraploid cells for each of the four groups of cells examined. Also, the total length of the dendritic arbors in tetraploid brain cells increased significantly by factors ranging from 1.4 to 2.4 times the total length of the analogous processes in diploid cells. Tetraploid neurons in the telencephalon and hypothalamus increased their arbor lengths predominantly by increasing the number of dendritic branches, while maintaining the average distance between branch points in the dendritic segments. In contrast, the tetraploid large pear-shaped neurons in the optic tectum had significantly longer terminal dendritic segments than the analogous diploid neurons, although these tetraploid neurons maintained their average number of dendritic segments per cell. Tetraploid tectal radial glial cells appeared to increase both their number of branches and the lengths of their terminal segments. Thus, the mode by which tetraploid brain cells achieved longer dendritic arbors varied from cell type to cell type. These results suggest a hypothetical basis for possible effects of genomic size on vertebrate brain structure and evolution at the cellular level.

Animals↗

PubMed1989

Pharmacokinetics of metapramine and its demethylated metabolites in plasma and brain of mice.

Previous studies on pharmacokinetic parameters of tricyclic antidepressants (TCAs) in rodents have shown different results from those obtained for the same drugs in man. The kinetics of metapramine (META) and its major demethylated metabolites (METs) were studied in the SWISS CD 1 mouse after acute administration in order to establish the pharmacokinetic parameters in plasma and brain. The plasma half-life (T1/2) was very short (87 min) compared with the half-life (7 h) in man. The metabolism of META was intensive as was the transfer of META and its metabolites into the brain. The kinetic profiles of the substances were quite similar both in plasma and in brain, namely a bicompartment open model. META was rapidly absorbed (Tmax = 10 min) into and quickly eliminated (T 1/2 = 40 min) from the brain. These parameters were used to schedule sampling (blood and brain) at the appropriate time after acute administration of increased doses. The administered doses were significantly correlated to firstly the plasma or brain levels of META, secondly the plasma levels of the main monodemethylated metabolite (MET I), and thirdly the plasma or brain levels of META + METs. Finally, the evolution of plasma and brain levels of the substances was studied after repeated injections (i.e. every 40 min) and confirmed the high affinity of META and its metabolites for the brain regions.

Animals↗

PubMed2003

Changing metabolic and energy profiles in fetal, neonatal, and adult rat brain.

The regional energy status and the availability of metabolic substrates during brain development are important, since a variety of fetal metabolic insults have been increasingly implicated in the evolution of neonatal brain disorders. The response of the brain to a metabolic insult is determined, in large part, by the ability to utilize the various substrates for intermediary metabolism in order to maintain energy stores within the tissue. To ascertain if metabolic conditions of the fetal brain make it more or less vulnerable to a stress, the high-energy phosphates and glucose-related compounds were examined in five regions of the embryonic day 18 (E-18) fetal brain. Glucose and glycogen levels in the E-18 fetal brain were generally higher in the cerebellum and its neuroepithelium than in the hippocampus, cerebral cortex, and its neuroepithelium. Regional lactate and high-energy phosphate concentrations were essentially the same in the five regions. Subsequently, the metabolic profile was examined in the cerebral cortex and striatum from E-18, postpartum day 7 (P-7) and adult rats. At the various stages of development, there were only minimal differences in the high-energy phosphate levels in the striatum and cortex. Glucose levels, the primary substrate in the adult brain, were essentially unchanged throughout development. In contrast, lactate was significantly elevated by 6- and 2-fold over those in the adult brain in the E-18 and P-7 striatum and cortex, respectively. Another alternative substrate, beta-hydroxybutyrate, was also significantly elevated at E-18 and increased more than 2-fold at P-7, but was barely detectable in the adult cortex and striatum. Finally, glucose and lactate levels were examined in cerebrospinal fluid, blood, and brain from the E-18 brain to determine if a gradient among the compartments exists. The levels of both lactate and glucose exhibited a concentration gradient in the E-18 fetus: blood > cerebrospinal fluid > brain parenchyma. The results indicate that energy state in the fetal brain is comparable to that in the neonates and the adults, but that the availability of alternative substrates for intermediary metabolism change markedly with development. The age-dependent substrate specificity for intermediary metabolism could affect the response of the fetal brain to a metabolic insult.

3-Hydroxybutyric Acid↗

PubMed2001

New perspectives on the evolution of protochordate sensory and locomotory systems, and the origin of brains and heads.

Cladistic analyses generally place tunicates close to the base of the chordate lineage, consistent with the assumption that the tunicate tail is primitively simple, not secondarily reduced from a segmented trunk. Cephalochordates (i.e. amphioxus) are segmented and resemble vertebrates in having two distinct locomotory modes, slow for distance swimming and fast for escape, that depend on separate sets of motor neurons and muscle cells. The sense organs of both amphioxus and tunicate larvae serve essentially as navigational aids and, despite some uncertainty as to homologies, current molecular and ultrastructural data imply a close relationship between them. There are far fewer signs of modification and reduction in the amphioxus central nervous system (CNS), however, so it is arguably the closer to the ancestral condition. Similarities between amphioxus and tunicate sense organs are then most easily explained if distance swimming evolved before and escape behaviour after the two lineages diverged, leaving tunicates to adopt more passive means of avoiding predation. Neither group has the kind of sense organs or sensory integration centres an organism would need to monitor predators, yet mobile predators with eyes were probably important in the early Palaeozoic. For a predator, improvements in vision and locomotion are mutually reinforcing. Both features probably evolved rapidly and together, in an 'arms race' of eyes, brains and segments that left protochordates behind, and ultimately produced the vertebrate head.

Animals↗

PubMed1988

Brain/body relations among myomorph rodents.

The observed increase in brain size (E) with body size (P) 'from mouse to elephant' may be described by a power relation E = kPb, where b is near 2/3 or 3/4. That this reflects a single, strong interaction between brain and body evolution is challenged by two observations: (1) different species with the same body size may have markedly different brain sizes, and (2) the value of b at the species level is usually nearer 1/3 than 2/3. Furthermore, the idea that a bigger brain means greater versatility on the part of its owner makes a strong statement about such animals. We examined these notions by measuring cranial volumes of 1,480 skulls from 62 subspecies of cricetid and murid rodents. Values of k and b were obtained by computing a reduced major axis on E and P across all specimens (b = 0.693), and when specimens were partitioned by genus (b = 0.456) and subspecies level (b = 0.338). Thus, the overall slope of 7/10 is not a simple extension of the developmental rules at the subspecies level (b near 1/3) nor even at the genus level (b near 4/9). Rather, it may reflect the most likely path for an interbreeding population subjected to varying selective pressures on one or more correlated traits. Furthermore, among the rodents studied, folivorous subspecies averaged about 2/3 as much brain as granivorous, insectivorous or generalist subspecies of the same body weight. Also, Old World rats, which may be more versatile than wood rats, gained their competitive advantage despite having relatively smaller brains.

Age Factors↗

PubMed1981

Frequency of primary brain stem lesions after head injuries. A CT scan analysis from 186 cases of severe head trauma.

Analysis of level of brain stem dysfunction, evolution, and CT scan profile was made on 76 cases of head injuries with prolonged unconsciousness and without hemispheric focal lesion and midline shift on CT scan. Eleven cases were considered normal on CT scan. The CT scan aspect of primary brain stem lesion was identified in 31.5% of these series, and in 14.5% of all severe head traumas (186 cases), from which this series is taken. Primary and secondary CT scan profiles were observed whatever the clinical level of dysfunction and its evolution. Pontine lesions were mainly associated with haemorrhage in the brain stem and diffuse brain swelling; but minimal signs (cortical level) and benign outcome can also be related to axial haemorrhage. These results emphasize the frequency of primary brain stem lesions and the value of CT scan in head injuries.

Brain Diseases↗

PubMed1989

[Primary hematoma of the brain stem: considerations apropos of a case].

The case of a 48 year-old woman presenting with a primary pontine hematoma is reported. The clinical evolution simulated a brain stem tumor and the diagnosis of hematoma was not established before the operation. The preoperative neurological deficit improved except for a facial nerve palsy. These hematomas are thought to be due to rupture of "cryptic" arteriovenous malformations and should be differentiated from those secondary to systemic hypertension. The diagnosis of brain stem hematomas should be considered in any case of brain stem lesion, especially in young and normotensive patients.

Cerebral Hemorrhage↗

PubMed2003

Diversification of brain and sense organ morphology in Antarctic dragonfishes (Perciformes: Notothenioidei: Bathydraconidae).

In the subzero shelf waters of Antarctica, fishes of the perciform suborder Notothenioidei dominate the fish fauna and constitute an adaptive radiation and a species flock. The 16 species of dragonfishes of the family Bathydraconidae live from surface waters to nearly 3,000 m and have the greatest overall depth range among notothenioid families. We examined the anatomy and histology of the brain, retina, and cephalic lateral line system of nine bathydraconid species representing 8 of the 11 known genera. We evaluate these data against a cladogram identifying three clades in the family. We provide a detailed drawing of the brain and cranial nerves of Gymnodraco acuticeps and Akarotaxis nudiceps. Bathydraconid brain morphology falls into two categories. Brains of most species are similar to those of generalized perciforms and some basal notothenioids (Class I). However, brains of deep-living bathydraconids (members of the tribe Bathydraconini minus Prionodraco) have a reduced telencephalon and tectum that renders the neural axis visible - the stalked brain morphology (Class II). All bathydraconids have duplex (rod and cone) retinae but there is considerable interspecific variation in the ratio of cones:rods and in the number of cells in the internal nuclear layer. Retinal histology reflects habitat depth but is not tightly coupled to phylogeny. Although the deep-living species of Bathydraconini have rod-dominated retinae, the retinae of some sister species are photopic. An expanded cephalic lateral line system is also characteristic of all members of the Bathydraconini as exemplified by Akarotaxis. This morphology includes large lateral line pores, wide membranous canals, hypertrophied canal neuromasts, and large anterodorsal lateral line nerves, eminentia granulares, and crista cerebellares. The saccular otoliths are also enlarged in members of this tribe. Neural diversification among bathydraconids on the Antarctic shelf has not involved the evolution of sensory specialists. Brain and sense organ morphologies do not approach the specialized condition seen in primary deep-sea fishes or even that of some secondary deep-sea fishes including sympatric non-notothenioids such as liparids (snailfishes) and muraenolepidids (eel cods). The brains and sense organs of bathydraconids, including the deep-living species, reflect their heritage as perciform shorefishes.

Anatomy, Comparative↗

PubMed1986

Trophic molecules and evolution of the nervous system.

Although recent work has reemphasized the general importance of ontogeny in evolution, underlying developmental molecular mechanisms are largely undefined. What heritable ontogenetic mechanisms result in the evolution of new morphologies and functions? Such questions are particularly difficult in the nervous system, in which each of 10(11) neurons forms approximately equal to 10(4) specific interconnections. I propose that specific heritable, trophic interactions during development, which determine cell survival and pathway size, form a substrate for neural evolution. This model is based on the observation that neurons are vastly overproduced during ontogeny; neurons, their pathways and connections are dependent on target-derived trophic factors for developmental survival; and co-innervating, functionally and anatomically distinct neural populations compete for common trophic factors for survival. Focusing on sympathetic and sensory neurons, which require the target-derived, trophic protein nerve growth factor at different times for developmental survival, and which innervate common targets, different classes of ontogenetic evolutionary mechanisms may be characterized. Evolution may occur from heritable changes in the structure of trophic gene products or altered timing of expression. Molecular mechanisms underlying heterochrony are thereby described. The model is directly applicable to evolution of the brain and is testable in a variety of situations.

Biological Evolution↗

PubMed2005

ventral veins lacking is required for specification of the tritocerebrum in embryonic brain development of Drosophila.

The homeotic or Hox genes encode a network of conserved transcription factors which provide axial positional information and control segment morphology in development and evolution. During embryonic brain development of Drosophila, the Hox gene labial (lab) is essential for tritocerebral neuromere specification; lab loss of function results in tritocerebral cells that fail to adopt a neuronal identity, causing axonal pathfinding defects. Here we present evidence that the POU-homeodomain DNA-binding protein ventral veins lacking (vvl) acts genetically downstream of lab in the specification of the tritocerebral neuromere. In the embryonic brain, vvl expression is seen in all brain neuromeres, including the tritocerebral lab domain. Lab mutant analysis shows that vvl expression in the tritocerebrum is dependent on lab activity. Loss-of-function analysis focussed on the tritocerebrum reveals that inactivation of vvl results in patterning defects which are comparable to the brain phenotype caused by null mutation of lab. In the absence of vvl, mutant tritocerebral cells are generated and positioned correctly, but these cells fail to express neuronal markers indicating defects in neuronal differentiation. Moreover, longitudinal axon pathways in the tritocerebrum are severely reduced or absent and the tritocerebral commissure is missing in the vvl mutant brain. Genetic rescue experiments show that vvl is able to partially replace lab in the specification of the tritocerebral neuromere. Our results indicate that vvl acts downstream of the Hox gene lab and regulates specific aspects of neuronal differentiation within the tritocerebral neuromere during embryonic brain development of Drosophila.

Animals↗

PubMed2005

Structural brain imaging of attention-deficit/hyperactivity disorder.

Many investigators have hypothesized that attention-deficit/hyperactivity disorder (ADHD) involves structural and functional brain abnormalities in frontal-striatal circuitry. Although our review suggests that there is substantial support for this hypothesis, a growing literature demonstrates widespread abnormalities affecting other cortical regions and the cerebellum. Because there is only one report studying adults with ADHD, this summary is based on children. A key limitation of the literature is that most of the studies until recently have been underpowered, using samples of fewer than 20 subjects per group. Nevertheless, these studies are largely consistent with the most comprehensive and definitive study (Castellanos et al 2002). Moreover, studies differ in the degree to which they address the influence of medications, comorbidities, or gender, and most have not addressed potentially important sources of heterogeneity such as family history of ADHD, subtype, or perinatal complications. Despite these limitations, a relatively consistent picture has emerged. The most replicated alterations in ADHD in childhood include significantly smaller volumes in the dorsolateral prefrontal cortex, caudate, pallidum, corpus callosum, and cerebellum. These results suggest that the brain is altered in a more widespread manner than has been previously hypothesized. Developmental studies are needed to address the evolution of this brain disorder into adulthood.

Adult↗

PubMed1989

Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy.

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.

Animals↗

PubMed1989

Gradiental approach to neocortical functional organization.

Examination of neuropsychological syndromes suggests strong congruence between neuroanatomical and functional neocortical metrics. Two cortical syndromes disrupt cognitively close functions if and only if their neuroanatomical territories are close. To capture this relationship, the concept of a cognitive gradient is introduced as a basic unit of macroscopic neocortical brain-behavioral analysis. A cognitive gradient is a continuous distribution of related functions along an axis defined at its extremes by a pair of sensory projection or motor areas. Cortical gradiental structure is viewed as a fundamental symmetric organization on which hemispheric elaborations are superimposed. The gradiental structure of the left hemisphere is presented in detail as an illustration of the concept. It is presumed that a similar set of elaborations can be uncovered for the right hemisphere. The gradiental model implies that at least from the macroscopic standpoint, functional neocortical organization is to a substantial degree continuous, interactive, and emergent, as opposed to mosaic, modular, and prededicated. It is proposed that a shift from latter to former properties signified a major development in the evolution of the brain. Thalamo-cortical integration may represent coexistence of evolutionally early and recent principles of cerebral organization.

Agnosia↗

PubMed1988

Mechanical effect of vocalization on human brain and meninges.

Vibrations of human skull, as produced by loud vocalisation, exert a massaging effect on the brain and facilitate elution of metabolic products from the brain into the cerebrospinal fluid (CSF). In addition, these vibrations, through their effect on arachnoid villi, speed up the flow of CSF from the subarachnoid space into the blood within the superior sagittal sinus and lacunae lateralis. In this way, the speed of renewal of CSF is increased, which again contributes to a faster cleaning process of the brain. The most important feature of human evolution is enlargement of the brain. This by itself would not be enough. The Neandertals had a brain 15% larger than we have, yet they did not survive in competition with modern humans. Their brains were more polluted, because their massive skulls did not vibrate and therefore the brains were not sufficiently cleaned. In the evolution of modern humans the thinning of cranial bones was important. In addition, the chin remained jutting out of the face as in no other hominids, in order to maintain the distance from the chin to the hyoid bone equal to the distance from the latter to the styloid process. This situation facilitates transmission of laryngeal vibrations onto the skull base via the mandible.

Brain↗

PubMed1985

Size and shape of the cerebral cortex in mammals. I. The cortical surface.

The evolution of the brain in mammals has been accompanied by a progressive enlargement of the cerebral cortex. Allometric analysis of the volume, surface and convolutedness of this cortex shows that among mammals two major groups can be distinguished: (1) species with lissencephalic brains, where surface-volume relationships are determined by linear geometric laws, and (2) species with gyrencephalic brains, where strict geometric similarity no longer applies. Different mathematical models are required to describe the brain morphology in these groups. It has been shown, moreover, that among species with convoluted brains, marine mammals (Cetacea) form a subgroup in that the cerebrocortical surface in these animals is more folded than in terrestrial mammals of similar brain size. Thus it appears that the use of a single allometric relation in studying the effect of size increase on the geometry of the brain - irrespective of convolutedness or ecological strategy - as has been done in previous studies, is unjustified and obscures the differences in the structural organization of mammalian brains. Finally, a dimensionless index of cortical folding is proposed, which indicates that the degree of cortical folding depends not only on the volume of the brain or cortex but on cortical thickness as well.

Animals↗