|
| ||
|
|
||
Brain Growth (brain + growth)
Selected AbstractsDose-dependent long-term effects of Tat in the rat hippocampal formation: A design-based stereological studyHIPPOCAMPUS, Issue 4 2010Sylvia Fitting Abstract The human immunodeficiency virus type 1 (HIV-1) protein transactivator of transcription (Tat) is believed to play a critical role in mediating central nervous system (CNS) pathology in pediatric HIV-1 infection. Long-term neurotoxicity was investigated in a design-based stereology study following intrahippocampal injection of Tat on postnatal day (P)10, a time period that approximates the peak in the rats' rate of brain growth and mimics clinical HIV-1 CNS infection at labor/delivery. The goal was to examine the impact of P10 intrahippocampal Tat injection on the anatomy of the adult hippocampus (5 month) to gain a better understanding about how timing of infection influences the rate of progression of pediatric HIV-1 infection [cf. Fitting et al. (2008a) Hippocampus 18:135,147]. Male P10 Sprague-Dawley rats were bilaterally injected with vehicle or one of three different doses of Tat (5, 25, or 50 ,g). Unbiased stereological estimates were used to quantify total neuron number (Nissl stain) in five major subregions of the rat hippocampus: granular layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB). Glial cells (astrocytes and oligodendrocytes) were quantified in the DGH and SUB. No significant reduction of neuron number was noted for any of the five hippocampal subregions, in contrast to the very prominent reductions reported when Tat was administered on P1 [Fitting et al. (2008a) Hippocampus 18:135,147]. However, for glial cells, the number of astrocytes in the DGH and SUB as well as the number of oligodendrocytes in the DGH were linear dose dependently increased as a function of dose of Tat. In conjunction with previous stereological research [Fitting et al., (2008a) Hippocampus 18:135,147], the present data suggest that variability in the progression of pediatric HIV/acquired immunodeficiency syndrome (AIDS) may be better understood with the knowledge of the factor of timing of HIV-1 CNS infection. © 2009 Wiley-Liss, Inc. [source] Neuroimaging of cortical development and brain connectivity in human newborns and animal modelsJOURNAL OF ANATOMY, Issue 4 2010Gregory A. Lodygensky Abstract Significant human brain growth occurs during the third trimester, with a doubling of whole brain volume and a fourfold increase of cortical gray matter volume. This is also the time period during which cortical folding and gyrification take place. Conditions such as intrauterine growth restriction, prematurity and cerebral white matter injury have been shown to affect brain growth including specific structures such as the hippocampus, with subsequent potentially permanent functional consequences. The use of 3D magnetic resonance imaging (MRI) and dedicated postprocessing tools to measure brain tissue volumes (cerebral cortical gray matter, white matter), surface and sulcation index can elucidate phenotypes associated with early behavior development. The use of diffusion tensor imaging can further help in assessing microstructural changes within the cerebral white matter and the establishment of brain connectivity. Finally, the use of functional MRI and resting-state functional MRI connectivity allows exploration of the impact of adverse conditions on functional brain connectivity in vivo. Results from studies using these methods have for the first time illustrated the structural impact of antenatal conditions and neonatal intensive care on the functional brain deficits observed after premature birth. In order to study the pathophysiology of these adverse conditions, MRI has also been used in conjunction with histology in animal models of injury in the immature brain. Understanding the histological substrate of brain injury seen on MRI provides new insights into the immature brain, mechanisms of injury and their imaging phenotype. [source] The pattern of endocranial ontogenetic shape changes in humansJOURNAL OF ANATOMY, Issue 3 2009Simon Neubauer Abstract Humans show a unique pattern of brain growth that differentiates us from all other primates. In this study, we use virtual endocasts to provide a detailed description of shape changes during human postnatal ontogeny with geometric morphometric methods. Using CT scans of 108 dried human crania ranging in age from newborns to adults and several hundred landmarks and semi-landmarks, we find that the endocranial ontogenetic trajectory is curvilinear with two bends, separating three distinct phases of shape change. We test to what extent endocranial shape change is driven by size increase and whether the curved ontogenetic trajectory can be explained by a simple model of modular development of the endocranial base and the endocranial vault. The hypothesis that endocranial shape change is driven exclusively by brain growth is not supported; we find changes in endocranial shape after adult size has been attained and that the transition from high rates to low rates of size increase does not correspond to one of the shape trajectory bends. The ontogenetic trajectory of the endocranial vault analyzed separately is nearly linear; the trajectory of the endocranial base, in contrast, is curved. The endocranial vault therefore acts as one developmental module during human postnatal ontogeny. Our data suggest that the cranial base comprises several submodules that follow their own temporally and/or spatially disjunct growth trajectories. [source] Noggin Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2007Gregory M Cooper PhD Abstract Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis. Introduction: Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, which causes secondary deformations of the cranial vault, cranial base, and brain. Current surgical intervention involves extirpation of the fused suture to allow unrestricted brain growth. However, resynostosis of the extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well-described inducers of ossification, are involved in bone healing. This study tested the hypothesis that a postoperative treatment with Noggin, an extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human familial nonsyndromic craniosynostosis. Materials and Methods: Thirty-one New Zealand white rabbits with bilateral coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a slow-resorbing collagen vehicle (n = 10). At 10 days of age, a 3 × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan reconstructions of the defects and standard radiographs were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histological analysis. Results: Radiographic analysis revealed that Noggin-treated animals had significantly greater coronal suture marker separation by 25 days and significantly greater craniofacial length at 84 days of age compared with controls. 3D-CT analysis revealed that Noggin treatment led to significantly greater defect areas through 84 days and to increased intracranial volumes at 84 days of age compared with other groups. Histological analysis supported CT data, showing that the untreated and BSA-treated groups had significant healing of the suturectomy site, whereas the Noggin-treated group had incomplete wound healing. Conclusions: These data support our hypothesis that inhibition of BMP activity using Noggin may prevent postoperative resynostosis in this rabbit model. These findings also suggest that Noggin therapy may have potential clinical use to prevent postoperative resynostosis in infants with craniosynostosis. [source] Functions and pathophysiological roles of phospholipase D in the brainJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Jochen Klein Abstract Ten years after the isoforms of mammalian phospholipase D (PLD), PLD1 and 2, were cloned, their roles in the brain remain speculative but several lines of evidence now implicate these enzymes in basic cell functions such as vesicular trafficking as well as in brain development. Many mitogenic factors, including neurotransmitters and growth factors, activate PLD in neurons and astrocytes. Activation of PLD downstream of protein kinase C seems to be a required step for astroglial proliferation. The characteristic disruption of the PLD signaling pathway by ethanol probably contributes to the delay of brain growth in fetal alcohol syndrome. The post-natal increase of PLD activities concurs with synapto- and myelinogenesis in the brain and PLD is apparently involved in neurite formation. In the adult and aging brain, PLD activity has antiapoptotic properties suppressing ceramide formation. Increased PLD activities in acute and chronic neurodegeneration as well as in inflammatory processes are evidently due to astrogliosis and may be associated with protective responses of tissue repair and remodeling. ARF-regulated PLD participates in receptor endocytosis as well as in exocytosis of neurotransmitters where PLD seems to favor vesicle fusion by modifications of the shape and charge of lipid membranes. Finally, PLD activities contribute free choline for the synthesis of acetylcholine in the brain. Novel tools such as RNA interference should help to further elucidate the roles of PLD isoforms in brain physiology and pathology. [source] Mitogenic effects of phospholipase D and phosphatidic acid in transiently permeabilized astrocytes: effects of ethanolJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Beate Schatter Abstract Investigations of lipid-mediated signalling pathways are often limited by a lack of methods for the intracellular delivery of lipid messengers. We established a procedure for the transient permeabilization of astrocytes by an oxygen-insensitive mutant of streptolysin-O (SLO) to investigate the participation of the phospholipase D (PLD) signalling pathway in astroglial cell proliferation. Exogenous PLD, when incubated in the presence of SLO, caused an increase in DNA synthesis (measured by thymidine incorporation) which was completely suppressed by ethanol (0.3%, v/v). In parallel experiments, phosphatidic acid also induced a dose-dependent mitogenic response which, however, was not affected by the presence of ethanol. Phosphatidic acid was more effective in this assay than diacylglycerol but its effect was sensitive to the protein kinase inhibitor Ro 31-8220. Our findings provide direct evidence that disruption of the PLD signalling pathway by ethanol is sufficient to suppress astroglial proliferation, an effect that might contribute to the inhibition of brain growth in alcoholic embryopathy. [source] Brains versus brawn: An empirical test of Barker's brain sparing modelAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2010Jack Baker The Barker model of the in utero origins of diminished muscle mass in those born small invokes the adaptive "sparing" of brain tissue development at the expense of muscle. Though compelling, to date this model has not been directly tested. This article develops an allometric framework for testing the principal prediction of the Barker model,that among those born small muscle mass is sacrificed to spare brain growth,then evaluates this hypothesis using data from the third National Health and Nutrition Examination Survey (NHANES III). The results indicate clear support for a negative relationship between the allometric development of the two tissues; however, a further consideration of conserved mammalian fetal circulatory patterns suggests the possibility that system-constrained patterns of developmental damage and "bet-hedging" responses in affected tissues may provide a more adequate explanation of the results. Far from signaling the end of studies of adaptive developmental programming, this perspective may open a promising new avenue of inquiry within the fields of human biology and the developmental origins of health and disease. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization without aquatic constraintAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2007Bryce A. Carlson Reconstructing evolutionary processes in the distant past is necessarily an inductive endeavor, typically appealing to numerous considerations thought to be relevant to the veracity of a particular conclusion. In this respect, it is essential that the considerations invoked to support hypotheses are in turn well-established truths. It is with these concerns that we sought to examine the nutritional, physiological, and archeological premises underlying the perspective that access to an aquatic diet rich in docosahexaenoic acid (DHA, 22:6n -3) was critical to human brain evolution (Carlson and Kingston [2007]: Am J Hum Biol 19:132,141). In our report investigating links between omega-3 (n -3) fatty acids and hominin encephalization, we concluded that the regular consumption of aquatic resources rich in preformed DHA may not have been essential given a varied diet of wild terrestrial foods (Carlson and Kingston [2007]). This assessment was based primarily on evidence of potential physiological adaptations in modern humans to ensure sufficient availability of DHA during critical periods of brain growth. While modern human physiology provides critical information regarding DHA as a constraint in evolving a large brain, it is also important to consistently contextualize interpretations within a framework of eclectic foraging diets rather than nutritionally limited modern agricultural populations or even modern foragers. We contend that current interpretations of Pleistocene hominin nutritional ecology do not uniquely support a shore-based foraging niche as claimed by Cunnane et al. ([2007]: Am J Hum Biol, 19:578,581). Specific issues raised in response to our article by Cunnane et al. and Joordens et al. ([2007]: Am J Hum Biol, 19:582,584) are addressed here. Am. J. Hum. Biol. 19:585,588, 2007. © 2007 Wiley-Liss, Inc. [source] Ring chromosome 6 in three fetuses: Case reports, literature review, and implications for prenatal diagnosisAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2002Maik Urban Abstract Prenatal and postnatal findings in three fetuses with a ring chromosome 6 are presented, and the literature of this rare cytogenetic disorder is reviewed. The described fetuses illustrate the broad spectrum of the clinical manifestation of ring chromosome 6. In one fetus, the disorder was diagnosed incidentally by a routine amniocentesis due to advanced maternal age. The other two fetuses were hydrocephalic and had other congenital anomalies. Remarkably, the ring chromosome 6 tends to disappear in cultured amniotic fluid cells; karyotyping revealed complete or nearly complete monosomy 6. In contrast, the ring was preserved in high proportions of fetal leukocytes. Postnatal growth retardation is the only consistent finding of this chromosomal disorder. Maternal age is not significantly above average. An additional review of 20 literature cases revealed a striking tendency to hydrocephalus, either due to deficient brain growth or secondary to an aqueductal stenosis. Children with hydrocephalus and ring chromosme 6 tend to display facial dysmorphism and may have additional malformations, growth failure, eye anomalies, and seizures. In contrast, there are two reports on children with a ring chromosome 6 who had short stature, normal appearance, and a normal or almost-normal psychomotor development. In such patients at the mild end of the clinical spectrum, the phenotype is basically restricted to what Kosztolányi. [1987: Hum Genet 75:174,179] delineated as "ring syndrome," comprising "severe growth failure without major malformations, without a specific deletion syndrome, with only a few or no minor anomalies, and mild to moderate mental retardation." This "ring syndrome" is considered to occur independently of the autosome involved in the ring formation. The overall impression from our cases and from the literature review of cases with ring chromosome 6 is that the karyotype-genotype correlation is poor. This makes prognostic counseling of parents difficult and unsatisfactory. Serial targeted ultrasound examinations, especially of the brain, are decisive factors in elucidating the prognosis. © 2002 Wiley-Liss, Inc. [source] | ||||||||||