The Response of Cerebral Cortex to Haemorrhagic Damage: Experimental Evidence from a Penetrating Injury Model

PubMed Central

Purushothuman, Sivaraman; Marotte, Lauren; Stowe, Sally; Johnstone, Daniel M.; Stone, Jonathan

2013-01-01

Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer’s disease). In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3–5 months. Brains were examined after 1–30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP), for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer’s disease was examined with the same techniques. Needlestick injury induced long-lasting changes–haem deposition, cell death, plaque-like deposits and glial invasion–along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the possibility that haemorrhagic damage to the brain can lead to plaque-like pathology. PMID:23555765

Increased Glutamate Receptor and Transporter Expression in the Cerebral Cortex and Striatum of Gcdh -/- Mice: Possible Implications for the Neuropathology of Glutaric Acidemia Type I

PubMed Central

Lagranha, Valeska Lizzi; Matte, Ursula; de Carvalho, Talita Giacomet; Seminotti, Bianca; Pereira, Carolina Coffi; Koeller, David M.; Woontner, Michael; Goodman, Stephen I.; de Souza, Diogo Onofre Gomes; Wajner, Moacir

2014-01-01

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh -/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh -/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh -/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh -/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh -/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh -/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh -/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I. PMID:24594605

Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

PubMed

Lagranha, Valeska Lizzi; Matte, Ursula; de Carvalho, Talita Giacomet; Seminotti, Bianca; Pereira, Carolina Coffi; Koeller, David M; Woontner, Michael; Goodman, Stephen I; de Souza, Diogo Onofre Gomes; Wajner, Moacir

2014-01-01

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh-/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model.

PubMed

Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

2016-01-15

Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary.

Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

PubMed Central

Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

2016-01-01

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

Regional microstructural organization of the cerebral cortex is affected by preterm birth.

PubMed

Bouyssi-Kobar, Marine; Brossard-Racine, Marie; Jacobs, Marni; Murnick, Jonathan; Chang, Taeun; Limperopoulos, Catherine

2018-01-01

To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort. We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 weeks; birthweight<1500 g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI. We studied 91 preterm infants at TEA and 69 full-term controls. Preterm infants demonstrated significantly higher diffusivity in the prefrontal, parietal, motor, somatosensory, and visual cortices suggesting delayed maturation of these cortical areas. Additionally, postnatal hydrocortisone treatment was related to accelerated microstructural organization in the prefrontal and somatosensory cortices. Preterm birth alters regional microstructural organization of the cerebral cortex in both neurocognitive brain regions and areas with primary sensory/motor functions. We also report for the first time a potential protective effect of postnatal hydrocortisone administration on cerebral cortical development in preterm infants.

Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

PubMed

Villa, R F; Ferrari, F; Gorini, A

2012-12-27

Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response.

PubMed

Thakare, Vishnu N; Aswar, Manoj K; Kulkarni, Yogesh P; Patil, Rajesh R; Patel, Bhoomika M

2017-10-01

Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique. Wistar rats were administered with silymarin at a dose of 100mg/kg and 200mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) level], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated. Rats subjected to OBX elicited significant increase in immobility time, ambulatory and rearing behaviors, reduced BDNF level, 5-HT, DA, NE and antioxidant parameters along with increased serum corticosterone, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex compared to sham operated rats. Administration of with silymarin significantly attenuated immobility time, ambulatory and rearing behaviors, serum corticosterone and improved BDNF expression, 5-HT, DA, NE and antioxidant paradigms in cerebral cortex as well as hippocampus. In addition, silymarin attenuated IL-6, and TNF-α significantly in hippocampus and cerebral cortex in OBX rats. Thus, silymarin exhibits anti-depressant-like activity in OBX rats due to alterations in several neurotransmitters, endocrine and immunologic systems, including BDNF, 5-HT, DA, NE, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex as well as serum corticosterone. Copyright © 2017 Elsevier Inc. All rights reserved.

A computational model of cerebral cortex folding.

PubMed

Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Stephen Miller, L; Liu, Tianming

2010-05-21

The geometric complexity and variability of the human cerebral cortex have long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3D geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: (1) Mechanical constraints of the skull regulate the cortical folding process. (2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. (3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. (4) The cortical folding pattern is dependent on the initial geometry of the cortex. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Acute intrastriatal injection of quinolinic acid provokes long-lasting misregulation of the cytoskeleton in the striatum, cerebral cortex and hippocampus of young rats.

PubMed

Pierozan, Paula; Gonçalves Fernandes, Carolina; Ferreira, Fernanda; Pessoa-Pureur, Regina

2014-08-19

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, considered to be involved in aging and some neurodegenerative disorders, including Huntington׳s disease. In the present work we have studied the long-lasting effect of acute intrastriatal injection of QUIN (150 nmol/0.5 µL) in 30 day-old rats on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits (NFL, NFM and NFH) respectively, until 21 days after injection. The acute administration of QUIN altered the homeostasis of IF phosphorylation in a selective manner, progressing from striatum to cerebral cortex and hippocampus. Twenty four hours after QUIN injection, the IFs were hyperphosphorylated in the striatum. This effect progressed to cerebral cortex causing hypophosphorylation at day 14 and appeared in the hippocampus as hyperphosphorylation at day 21 after QUIN infusion. PKA and PKCaMII have been activated in striatum and hippocampus, since Ser55 and Ser57 in NFL head domain were hyperphosphorylated. However, MAPKs (Erk1/2, JNK and p38MAPK) were hyperphosphorylated/activated only in the hippocampus, suggesting different signaling mechanisms in these two brain structures during the first weeks after QUIN infusion. Also, protein phosphatase 1 (PP1) and 2B (PP2B)-mediated hypophosphorylation of the IF proteins in the cerebral cortex 14 after QUIN injection reinforce the selective signaling mechanisms in different brain structures. Increased GFAP immunocontent in the striatum and cerebral cortex 24h and 14 days after QUIN injection respectively, suggests reactive astrocytes in these brain regions. We propose that disruption of cytoskeletal homeostasis in neural cells takes part of the long-lasting molecular mechanisms of QUIN toxicity in adolescent rats, showing selective and progressive misregulation of the signaling mechanisms targeting the IF proteins in the striatum, cerebral cortex and hippocampus with important implications for brain function. Copyright © 2014 Elsevier B.V. All rights reserved.

Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain.

PubMed

Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K

2016-05-01

Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease in the expression of HDAC-2 and miRNA-134 in the cerebral cortex. Copyright © 2016. Published by Elsevier Inc.

SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

PubMed

Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

2017-04-01

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro

PubMed Central

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P. C.; Livesey, Frederick J.

2015-01-01

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. PMID:26395144

An Evo-Devo Approach to Thyroid Hormones in Cerebral and Cerebellar Cortical Development: Etiological Implications for Autism

PubMed Central

Berbel, Pere; Navarro, Daniela; Román, Gustavo C.

2014-01-01

The morphological alterations of cortical lamination observed in mouse models of developmental hypothyroidism prompted the recognition that these experimental changes resembled the brain lesions of children with autism; this led to recent studies showing that maternal thyroid hormone deficiency increases fourfold the risk of autism spectrum disorders (ASD), offering for the first time the possibility of prevention of some forms of ASD. For ethical reasons, the role of thyroid hormones on brain development is currently studied using animal models, usually mice and rats. Although mammals have in common many basic developmental principles regulating brain development, as well as fundamental basic mechanisms that are controlled by similar metabolic pathway activated genes, there are also important differences. For instance, the rodent cerebral cortex is basically a primary cortex, whereas the primary sensory areas in humans account for a very small surface in the cerebral cortex when compared to the associative and frontal areas that are more extensive. Associative and frontal areas in humans are involved in many neurological disorders, including ASD, attention deficit-hyperactive disorder, and dyslexia, among others. Therefore, an evo-devo approach to neocortical evolution among species is fundamental to understand not only the role of thyroid hormones and environmental thyroid disruptors on evolution, development, and organization of the cerebral cortex in mammals but also their role in neurological diseases associated to thyroid dysfunction. PMID:25250016

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

PubMed

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

2015-09-15

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

Convection-enhanced delivery of AAV2 in white matter--a novel method for gene delivery to cerebral cortex.

PubMed

Barua, N U; Woolley, M; Bienemann, A S; Johnson, D; Wyatt, M J; Irving, C; Lewis, O; Castrique, E; Gill, S S

2013-10-30

Convection-enhanced delivery (CED) is currently under investigation for delivering therapeutic agents to subcortical targets in the brain. Direct delivery of therapies to the cerebral cortex, however, remains a significant challenge. We describe a novel method of targeting adeno-associated viral vector (AAV) mediated gene therapies to specific cerebral cortical regions by performing high volume, high flow rate infusions into underlying white matter in a large animal (porcine) model. Infusion volumes of up to 700 μl at flow rates as high as 10 μl/min were successfully performed in white matter without adverse neurological sequelae. Co-infusion of AAV2/5-GFP with 0.2% Gadolinium in artificial CSF confirmed transgene expression in the deep layers of cerebral cortex overlying the infused areas of white matter. AAV-mediated gene therapies have been previously targeted to the cerebral cortex by performing intrathalamic CED and exploiting axonal transport. The novel method described in this study facilitates delivery of gene therapies to specific regions of the cerebral cortex without targeting deep brain structures. AAV-mediated gene therapies can be targeted to specific cortical regions by performing CED into underlying white matter. This technique could be applied to the treatment of neurological disorders characterised by cerebral cortical degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

The organization of the human cerebellum estimated by intrinsic functional connectivity

PubMed Central

Krienen, Fenna M.; Castellanos, Angela; Diaz, Julio C.; Yeo, B. T. Thomas

2011-01-01

The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map. PMID:21795627

Perillaldehyde attenuates cerebral ischemia-reperfusion injury-triggered overexpression of inflammatory cytokines via modulating Akt/JNK pathway in the rat brain cortex.

PubMed

Xu, Lixing; Li, Yuebi; Fu, Qiang; Ma, Shiping

2014-11-07

Perillaldehyde (PAH), one of the major oil components in Perilla frutescens, has anti-inflammatory effects. Few studies have examined the neuroprotective effect of PAH on stroke. So the aim of our study is to investigate the effect of PAH on ischemia-reperfusion-induced injury in the rat brain cortex. Middle cerebral artery occlusion (MCAO) model was selected to make cerebral ischemia-reperfusion injury. Rats were assigned randomly to groups of sham, MCAO, and two treatment groups by PAH at 36.0, 72.0mg/kg. Disease model was set up after intragastrically (i.g.) administering for 7 consecutive days. The neurological deficit, the cerebral infarct size, biochemical parameters and the relative mRNA and protein levels were examined. The results showed that the NO level, the iNOS activity, the neurological deficit scores, the cerebral infarct size and the expression of inflammatory cytokines including interleukin (IL)-1β, interleukin (IL)-6 and tumor necrosis factor (TNF)-α were significantly decreased by PAH treatment. PAH also increased the Phospho-Akt level and decrease the Phospho-JNK level by Western blot analysis. Meanwhile, the PAH groups exhibited a dramatically decrease of apoptosis-related mRNA expression such as Bax and caspase-3. Our findings shown that PAH attenuates cerebral ischemia/reperfusion injury in the rat brain cortex, and suggest its neuroprotective effect is relate to regulating the inflammatory response through Akt /JNK pathway. The activation of this signalling pathway eventually inhibits apoptotic cell death induced by cerebral ischemia-reperfusion. Copyright © 2014 Elsevier Inc. All rights reserved.

Contralateral cerebello-thalamo-cortical pathways with prominent involvement of associative areas in humans in vivo.

PubMed

Palesi, Fulvia; Tournier, Jacques-Donald; Calamante, Fernando; Muhlert, Nils; Castellazzi, Gloria; Chard, Declan; D'Angelo, Egidio; Wheeler-Kingshott, Claudia A M

2015-11-01

In addition to motor functions, it has become clear that in humans the cerebellum plays a significant role in cognition too, through connections with associative areas in the cerebral cortex. Classical anatomy indicates that neo-cerebellar regions are connected with the contralateral cerebral cortex through the dentate nucleus, superior cerebellar peduncle, red nucleus and ventrolateral anterior nucleus of the thalamus. The anatomical existence of these connections has been demonstrated using virus retrograde transport techniques in monkeys and rats ex vivo. In this study, using advanced diffusion MRI tractography we show that it is possible to calculate streamlines to reconstruct the pathway connecting the cerebellar cortex with contralateral cerebral cortex in humans in vivo. Corresponding areas of the cerebellar and cerebral cortex encompassed similar proportion (about 80%) of the tract, suggesting that the majority of streamlines passing through the superior cerebellar peduncle connect the cerebellar hemispheres through the ventrolateral thalamus with contralateral associative areas. This result demonstrates that this kind of tractography is a useful tool to map connections between the cerebellum and the cerebral cortex and moreover could be used to support specific theories about the abnormal communication along these pathways in cognitive dysfunctions in pathologies ranging from dyslexia to autism.

Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

PubMed Central

Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M.; de Castro Leal, Maria E.; Bertelsen, Mads F.; Alagaili, Abdulaziz N.; Mohammad, Osama B.; Manger, Paul R.; Herculano-Houzel, Suzana

2017-01-01

Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran brains is not affected by domestication. Instead, large carnivorans appear to be particularly vulnerable to metabolic constraints that impose a trade-off between body size and number of cortical neurons. PMID:29311850

Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species.

PubMed

Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M; de Castro Leal, Maria E; Bertelsen, Mads F; Alagaili, Abdulaziz N; Mohammad, Osama B; Manger, Paul R; Herculano-Houzel, Suzana

2017-01-01

Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran brains is not affected by domestication. Instead, large carnivorans appear to be particularly vulnerable to metabolic constraints that impose a trade-off between body size and number of cortical neurons.

Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex.

PubMed

Jasmin, Luc; Rabkin, Samuel D; Granato, Alberto; Boudah, Abdennacer; Ohara, Peter T

2003-07-17

It is known that pain perception can be altered by mood, attention and cognition, or by direct stimulation of the cerebral cortex, but we know little of the neural mechanisms underlying the cortical modulation of pain. One of the few cortical areas consistently activated by painful stimuli is the rostral agranular insular cortex (RAIC) where, as in other parts of the cortex, the neurotransmitter gamma-aminobutyric acid (GABA) robustly inhibits neuronal activity. Here we show that changes in GABA neurotransmission in the RAIC can raise or lower the pain threshold--producing analgesia or hyperalgesia, respectively--in freely moving rats. Locally increasing GABA, by using an enzyme inhibitor or gene transfer mediated by a viral vector, produces lasting analgesia by enhancing the descending inhibition of spinal nociceptive neurons. Selectively activating GABA(B)-receptor-bearing RAIC neurons produces hyperalgesia through projections to the amygdala, an area involved in pain and fear. Whereas most studies focus on the role of the cerebral cortex as the end point of nociceptive processing, we suggest that cerebral cortex activity can change the set-point of pain threshold in a top-down manner.

Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

PubMed Central

Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

2014-01-01

The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex

PubMed Central

Toma, Kenichi; Hanashima, Carina

2015-01-01

Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes. PMID:26321900

Functional and structural mapping of human cerebral cortex: Solutions are in the surfaces

PubMed Central

Van Essen, David C.; Drury, Heather A.; Joshi, Sarang; Miller, Michael I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex. PMID:9448242

Functional and structural mapping of human cerebral cortex: solutions are in the surfaces

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.; Joshi, S.; Miller, M. I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.

Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain.

PubMed

Nazıroğlu, Mustafa; Kozlu, Süleyman; Yorgancıgil, Emre; Uğuz, Abdülhadi Cihangir; Karakuş, Kadir

2013-01-01

Oxidative stress is a critical route of damage in various physiological stress-induced disorders, including depression. Rose oil may be a useful treatment for depression because it contains flavonoids which include free radical antioxidant compounds such as rutin and quercetin. We investigated the effects of absolute rose oil (from Rosa × damascena Mill.) and experimental depression on lipid peroxidation and antioxidant levels in the cerebral cortex of rats. Thirty-two male rats were randomly divided into four groups. The first group was used as control, while depression was induced in the second group using chronic mild stress (CMS). Oral (1.5 ml/kg) and vapor (0.15 ml/kg) rose oil were given for 28 days to CMS depression-induced rats, constituting the third and fourth groups, respectively. The sucrose preference test was used weekly to identify depression-like phenotypes during the experiment. At the end of the experiment, cerebral cortex samples were taken from all groups. The lipid peroxidation levels in the cerebral cortex in the CMS group were higher than in control whereas their levels were decreased by rose oil vapor exposure. The vitamin A, vitamin E, vitamin C and β-carotene concentrations in the cerebral cortex were lower in the CMS group than in the control group whereas their concentrations were higher in the rose oil vapor plus CMS group. The CMS-induced antioxidant vitamin changes were not modulated by oral treatment. Glutathione peroxidase activity and reduced glutathione did not change statistically in the four groups following CMS or either treatment. In conclusion, experimental depression is associated with elevated oxidative stress while treatment with rose oil vapor induced protective effects on oxidative stress in depression.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A.

PubMed

Mathew, Jobin; Balakrishnan, Savitha; Antony, Sherin; Abraham, Pretty Mary; Paulose, C S

2012-02-24

Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis.

PubMed

Marshall, Randolph S; Asllani, Iris; Pavol, Marykay A; Cheung, Ying-Kuen; Lazar, Ronald M

2017-01-01

Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascular disease is unknown. We investigated the association between regional cortical blood flow and regional cortical thickness in patients with asymptomatic unilateral high-grade internal carotid artery disease without stroke. Twenty-nine patients underwent high resolution anatomical and single-delay, pseudocontinuous arterial spin labeling magnetic resonance imaging with partial volume correction to assess gray matter baseline flow. Cortical thickness was estimated using Freesurfer software, followed by co-registration onto each patient's cerebral blood flow image space. Paired t-tests assessed regional cerebral blood flow in motor cortex (supplied by the carotid artery) and visual cortex (indirectly supplied by the carotid) on the occluded and unoccluded side. Pearson correlations were calculated between cortical thickness and regional cerebral blood flow, along with age, hypertension, diabetes and white matter hyperintensity volume. Multiple regression and generalized estimating equation were used to predict cortical thickness bilaterally and in each hemisphere separately. Cortical blood flow correlated with thickness in motor cortex bilaterally (p = 0.0002), and in the occluded and unoccluded sides individually; age (p = 0.002) was also a predictor of cortical thickness in the motor cortex. None of the variables predicted cortical thickness in visual cortex. Blood flow was significantly lower on the occluded versus unoccluded side in the motor cortex (p<0.0001) and in the visual cortex (p = 0.018). On average, cortex was thinner on the side of occlusion in motor but not in visual cortex. The association between cortical blood flow and cortical thickness in carotid arterial territory with greater thinning on the side of the carotid occlusion suggests that altered cerebral hemodynamics is a factor in cortical thinning.

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

PubMed

Liang, Meng-Ya; Chen, Guang-Xian; Tang, Zhi-Xian; Rong, Jian; Yao, Jian-ping; Wu, Zhong-Kai

2016-03-01

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Tooele Army Depot - South Area Suspected Releases Units RCRA Facility Investigation - Phase II for SWMUs 1, 25, and 37. Appendices: D-M

DTIC Science & Technology

1995-11-01

VI) or to the acidity of the aerosol. Many cases of nasal mucosal injury (inflamed mucosa, ulcerated or perforated septum) in workers exposed to Cr0 3...degeneration in the cerebral cortex, marked chromatoloysis, nuclear changes in neurons, neuronal degenera- tion in the cerebral cortex accompanied by...by degeneration and death of nerves in the focal areas of the cerebral cortex (i.e. the largest part of the brain), loss of vision, speech impairment

Non-shivering thermogenesis during prostaglandin E1 fever in rats: role of the cerebral cortex.

PubMed

Monda, M; Amaro, S; De Luca, B

1994-07-18

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E1 (PGE1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc) and oxygen (O2) consumption were monitored during the fever from PGE1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, TIBAT, Tc and O2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE1-induced febrile response.

Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

ERIC Educational Resources Information Center

Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

2011-01-01

Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin.

PubMed

Ogino, Himari; Hisanaga, Arisa; Kohno, Takao; Kondo, Yuta; Okumura, Kyoko; Kamei, Takana; Sato, Tempei; Asahara, Hiroshi; Tsuiji, Hitomi; Fukata, Masaki; Hattori, Mitsuharu

2017-03-22

The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, noninvasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro , but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons. This enzyme was identified as a disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3). Recombinant ADAMTS-3 cleaved Reelin at the N-t site. ADAMTS-3 was expressed in excitatory neurons in the cerebral cortex and hippocampus. N-t cleavage of Reelin was markedly decreased in the embryonic cerebral cortex of ADAMTS-3 knock-out (KO) mice. Importantly, the amount of Dab1 and the phosphorylation level of Tau, which inversely correlate with Reelin activity, were significantly decreased in the cerebral cortex of ADAMTS-3 KO mice. Conditional KO mice, in which ADAMTS-3 was deficient only in the excitatory neurons of the forebrain, showed increased dendritic branching and elongation in the postnatal cerebral cortex. Our study shows that ADAMTS-3 is the major enzyme that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. Therefore, inhibition of ADAMTS-3 may be an effective treatment for neuropsychiatric and neurodegenerative disorders. SIGNIFICANCE STATEMENT ADAMTS-3 was identified as the protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. ADAMTS-3 was expressed in the excitatory neurons of the embryonic and postnatal cerebral cortex and hippocampus. Cleavage by ADAMTS-3 is the major contributor of Reelin inactivation in vivo Tau phosphorylation was decreased and dendritic branching and elongation was increased in ADAMTS-3-deficient mice. Therefore, inhibition of ADAMTS-3 upregulates Reelin activity and may be a potential therapeutic strategy for the prevention or treatment of neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. Copyright © 2017 the authors 0270-6474/17/373181-11$15.00/0.

Mapping visual cortex in monkeys and humans using surface-based atlases

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

2001-01-01

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice.

PubMed

Kumar, Dhiraj; Thakur, M K

2015-01-01

Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed. In the present study, we have examined the age-related changes in the expression of these proteins in cerebral cortex and hippocampus of 10-, 30-, 50-, and 80-week-old male mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated that messenger RNA (mRNA) level of Nrxn1 and Nlgn3 significantly increased from 10 to 30 weeks and then decreased at 50 weeks in both the regions. However, in 80-week-old mice, Nrxn1 and Nlgn3 were further downregulated in cerebral cortex while Nrxn1 was downregulated and Nlgn3 was upregulated in hippocampus. These findings were corroborated by immunoblotting and immunofluorescence results. When the expression of Nrxn1 and Nlgn3 was correlated with presynaptic density marker synaptophysin, it was found that synaptophysin protein expression in cerebral cortex was high at 10 weeks and decreased gradually up to 80 weeks, whereas in hippocampus, it decreased until 50 weeks and then increased remarkably at 80 weeks. Furthermore, Pearson's correlation analysis showed that synaptophysin had a strong relation with Nrxn1 and Nlgn3 in cerebral cortex and with Nlgn3 in hippocampus. Thus, these findings showed that Nrxn1 and Nlgn3 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during aging.

Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

PubMed

Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

2013-08-01

Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

Inhibition of cerebral ischemia/reperfusion injury-induced apoptosis: nicotiflorin and JAK2/STAT3 pathway.

PubMed

Hu, Guang-Qiang; Du, Xi; Li, Yong-Jie; Gao, Xiao-Qing; Chen, Bi-Qiong; Yu, Lu

2017-01-01

Nicotiflorin is a flavonoid extracted from Carthamus tinctorius. Previous studies have shown its cerebral protective effect, but the mechanism is undefined. In this study, we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway. The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion. Nicotiflorin (10 mg/kg) was administered by tail vein injection. Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining. Additionally, p-JAK2, p-STAT3, Bcl-2, Bax, and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay. Nicotiflorin altered the shape and structure of injured neurons, decreased the number of apoptotic cells, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax, decreased Bax immunoredactivity, and increased Bcl-2 protein expression and immunoreactivity. These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

Anosmia leads to a loss of gray matter in cortical brain areas.

PubMed

Bitter, Thomas; Gudziol, Hilmar; Burmeister, Hartmut Peter; Mentzel, Hans-Joachim; Guntinas-Lichius, Orlando; Gaser, Christian

2010-06-01

Chronic olfactory disorders, including the complete loss of the sense of smell (anosmia), are common. Using voxel-based morphometry (VBM) in magnetic resonance imaging (MRI), structural changes in the cerebral gray matter (GM) of a group of patients with anosmia compared with a normosmic, healthy control group were evaluated. Patients with anosmia presented a significant decrease of GM volume mainly in the nucleus accumbens with adjacent subcallosal gyrus, in the medial prefrontal cortex (MPC) including the middle and anterior cingulate cortices, and in the dorsolateral prefrontal cortex (dlPFC). These areas are part of the limbic loop of the basal ganglia and except the dlPFC secondary olfactory areas. They also play an important role in many neurological diseases. Furthermore, volume decreases in smaller areas like the piriform cortex, insular cortex, orbitofrontal cortex, hippocampus, parahippocampal gyrus, supramarginal gyrus, and cerebellum could be seen. Longer disease duration was associated with a stronger atrophy in the described areas. No local increases in the GM volume could be observed. A comparison with results of an additionally executed functional MRI study on olfaction in healthy subjects was performed to evaluate the significance of the observed atrophy areas in cerebral olfactory processing. To our knowledge, this is the first study on persisting structural changes in cortical GM volume after complete olfactory loss.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

PubMed Central

2012-01-01

Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders

NASA Astrophysics Data System (ADS)

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-01

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds’ Glx, Cho, Cr in the ACC and HCs’ mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds’ Glx and Cr in the PC and HCs’ mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders.

PubMed

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-21

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds' Glx, Cho, Cr in the ACC and HCs' mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds' Glx and Cr in the PC and HCs' mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

The preferential accumulation of heavy metals in different tissues following frequent respiratory exposure to PM2.5 in rats

PubMed Central

Li, Qingzhao; Liu, Huibin; Alattar, Mohamed; Jiang, Shoufang; Han, Jing; Ma, Yujiao; Jiang, Chunyang

2015-01-01

This study aimed to explore the pattern of accumulation of some of main heavy metals in blood and various organs of rats after exposed to the atmospheric fine particulate matter (PM2.5). Rats were randomly divided into control and three treatment groups (tracheal perfusion with 10 mg/kg, 20 mg/kg and 40 mg/kg of PM2.5 suspension liquid, respectively). Whole blood and the lung, liver, kidney, and cerebral cortex were harvested after rats were treated and sacrificed. The used heavy metals were detected using inductively coupled plasma-mass spectrometry (ICP-MS) instrument. As results, Lead was increased in the liver, lung and cerebral cortex and the level of manganese was significantly elevated in the liver and cerebral cortex in PM2.5 treated rats. Besides, arsenic was prominently enriched both in cerebral cortex and in blood, and so did the aluminum in the cerebral cortex and the copper in the liver. However, cadmium, chromium and nickel have shown no difference between the control group and the three PM2.5 treated groups. Following the exposure of PM2.5, different heavy metals are preferentially accumulated in different body tissues. PMID:26582271

Comparative Analysis of the Subventricular Zone in Rat, Ferret and Macaque: Evidence for an Outer Subventricular Zone in Rodents

PubMed Central

Camacho, Jasmin; Antczak, Jared L.; Prakash, Anish N.; Cziep, Matthew E.; Walker, Anita I.; Noctor, Stephen C.

2012-01-01

The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. Recent work has shown that precursor cells in the subventricular zone (SVZ) provide a major contribution to prenatal cortical neurogenesis, and that the SVZ is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. Identifying characteristics that are shared by or that distinguish cortical precursor cells across mammalian species will shed light on factors that regulate cortical neurogenesis and may point toward mechanisms that underlie the evolutionary expansion of the neocortex in gyrencephalic mammals. We immunostained sections of the developing cerebral cortex from lissencephalic rats, and from gyrencephalic ferrets and macaques to compare the distribution of precursor cell types in each species. We also performed time-lapse imaging of precursor cells in the developing rat neocortex. We show that the distribution of Pax6+ and Tbr2+ precursor cells is similar in lissencephalic rat and gyrencephalic ferret, and different in the gyrencephalic cortex of macaque. We show that mitotic Pax6+ translocating radial glial cells (tRG) are present in the cerebral cortex of each species during and after neurogenesis, demonstrating that the function of Pax6+ tRG cells is not restricted to neurogenesis. Furthermore, we show that Olig2 expression distinguishes two distinct subtypes of Pax6+ tRG cells. Finally we present a novel method for discriminating the inner and outer SVZ across mammalian species and show that the key cytoarchitectural features and cell types that define the outer SVZ in developing primates are present in the developing rat neocortex. Our data demonstrate that the developing rat cerebral cortex possesses an outer subventricular zone during late stages of cortical neurogenesis and that the developing rodent cortex shares important features with that of primates. PMID:22272298

Comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents.

PubMed

Martínez-Cerdeño, Verónica; Cunningham, Christopher L; Camacho, Jasmin; Antczak, Jared L; Prakash, Anish N; Cziep, Matthew E; Walker, Anita I; Noctor, Stephen C

2012-01-01

The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. Recent work has shown that precursor cells in the subventricular zone (SVZ) provide a major contribution to prenatal cortical neurogenesis, and that the SVZ is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. Identifying characteristics that are shared by or that distinguish cortical precursor cells across mammalian species will shed light on factors that regulate cortical neurogenesis and may point toward mechanisms that underlie the evolutionary expansion of the neocortex in gyrencephalic mammals. We immunostained sections of the developing cerebral cortex from lissencephalic rats, and from gyrencephalic ferrets and macaques to compare the distribution of precursor cell types in each species. We also performed time-lapse imaging of precursor cells in the developing rat neocortex. We show that the distribution of Pax6+ and Tbr2+ precursor cells is similar in lissencephalic rat and gyrencephalic ferret, and different in the gyrencephalic cortex of macaque. We show that mitotic Pax6+ translocating radial glial cells (tRG) are present in the cerebral cortex of each species during and after neurogenesis, demonstrating that the function of Pax6+ tRG cells is not restricted to neurogenesis. Furthermore, we show that Olig2 expression distinguishes two distinct subtypes of Pax6+ tRG cells. Finally we present a novel method for discriminating the inner and outer SVZ across mammalian species and show that the key cytoarchitectural features and cell types that define the outer SVZ in developing primates are present in the developing rat neocortex. Our data demonstrate that the developing rat cerebral cortex possesses an outer subventricular zone during late stages of cortical neurogenesis and that the developing rodent cortex shares important features with that of primates.

[A role of the autonomic nervous system in cerebro-cardiac disorders].

PubMed

Basantsova, N Yu; Tibekina, L M; Shishkin, A N

The authors consider anatomical/physiological characteristics and a role of different autonomic CNS regions, including insula cortex, amygdala complex, anterior cingulate cortex, ventral medial prefrontal cortex, hypothalamus and epiphysis, involved in the regulation of cardiovascular activity. The damage of these structures, e.g., due to the acute disturbance of cerebral blood circulation, led to arrhythmia, including fatal arrhythmia, in previously intact myocardium; systolic and diastolic dysfunction, ischemic changes considered in the frames of cerebro-cardial syndrome. On the cellular level, the disturbance of autonomic regulation resulted in catechol amine excitotoxicity, oxidative stress and free radical myocardium injury.

Absence of bundle structure in the neocortex of the reeler mouse at the embryonic stage. Studies by scanning electron microscopic fractography.

PubMed

Mikoshiba, K; Nishimura, Y; Tsukada, Y

The reeler mutant mouse is characterized by a derangement of the cerebral cortical structure due to abnormalities during the migration step at the embryonic stage. We have analyzed both the control and reeler cerebral cortex by means of scanning electron microscopic fractography. In the control cerebral cortex, the bundle formation was composed of fine fibers on which the migrating neuroblasts were attached perpendicular to the pial surface, whereas no bundle formation was observed in the reeler; instead, there was a fine meshwork of fibers surrounding the neuroblasts. The possible role of bundle formation in the normal cerebral cortex and the correlation between the inability of cells to migrate and the absence of bundle formation in the reeler is discussed.

Regulation of cerebral cortex development by Rho GTPases: insights from in vivo studies

PubMed Central

Azzarelli, Roberta; Kerloch, Thomas; Pacary, Emilie

2015-01-01

The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations. PMID:25610373

The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes.

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tyurina, Y Y; Tyurin, V A

2000-01-01

Glutamate is shown to induce increases in intracellular Ca2+ concentrations ([Ca2+]i), increases in 45Ca2+ influx, decreases in the activity of Na+,K+-ATPase activity, and activation of the Na+/Ca2+ exchanger in rat cerebral cortex synaptosomes. NMDA receptor antagonists virtually prevented these effects. Preincubation of synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 normalized [Ca2+]i, 45Ca2+ influx, and Na+,K+-ATPase activity in rat cerebral cortex synaptosomes exposed to glutamate. Glutamate and GM1 activated the Na+/K+ exchanger, and their effects were additive. Calcium ions entering cerebral cortex nerve cells via NMDA receptors during exposure to high glutamate concentrations appeared to be only the trigger for the processes activating free-radical reactions. Activation of these reactions led to increases in Ca2+ influx into cells, decreases in Na+,K+-ATPase activity, and significant increases in [Ca2+]i, though this could be prevented by antioxidants and gangliosides.

Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis.

PubMed

Fan, Xiaoying; Dong, Ji; Zhong, Suijuan; Wei, Yuan; Wu, Qian; Yan, Liying; Yong, Jun; Sun, Le; Wang, Xiaoye; Zhao, Yangyu; Wang, Wei; Yan, Jie; Wang, Xiaoqun; Qiao, Jie; Tang, Fuchou

2018-06-04

The cellular complexity of human brain development has been intensively investigated, although a regional characterization of the entire human cerebral cortex based on single-cell transcriptome analysis has not been reported. Here, we performed RNA-seq on over 4,000 individual cells from 22 brain regions of human mid-gestation embryos. We identified 29 cell sub-clusters, which showed different proportions in each region and the pons showed especially high percentage of astrocytes. Embryonic neurons were not as diverse as adult neurons, although they possessed important features of their destinies in adults. Neuron development was unsynchronized in the cerebral cortex, as dorsal regions appeared to be more mature than ventral regions at this stage. Region-specific genes were comprehensively identified in each neuronal sub-cluster, and a large proportion of these genes were neural disease related. Our results present a systematic landscape of the regionalized gene expression and neuron maturation of the human cerebral cortex.

Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat.

PubMed Central

Aiello-Malmberg, P; Bartolini, A; Bartolini, R; Galli, A

1979-01-01

1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-HT release in the caudate nucleus and increases it 3 fold in the cerebral cortex. The effects of the electrical stimulation of the raphe are potentiated by chlorimipramine. 3. Brain 5-HT release is greatly increased by morphine hydrochloride (6 mg/kg i.v.) and by physostigmine (100 microgram/kg i.v.), but not by DL-DOPA (50 mg/kg i.v.). 4. It is suggested that the 5-HT releasing action of physostigmine can contribute to some of its pharmacological effects such as the analgesic effect so far attributed exclusively to its indirect cholinomimetic activity. 5. The 5-HT releasing action of physostigmine seems unrelated to its anticholinesterase activity. PMID:435680

Amino Acid Neurotransmitters; Mechanisms of Their Uptake into Synaptic Vesicles

DTIC Science & Technology

1991-08-01

4.1.1.15), is localized in specific GABAergic nerve terminals (Fonnum et al, 1970). The subcortical telencephalon , which contains among others the...ratio between the vesicular uptake of GABA and glycine is similar in cerebral cortex, subcortical telencephalon , whole brain, and spinal cord. This is...regions, cerebral cortex, cerebellum, medulla and subcortical telencephalon (i.e. forebrain after removal of cortex). The vesicular uptake is low and

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

NASA Astrophysics Data System (ADS)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

PubMed

Bruno, Alessandra Nejar; Fontella, Fernanda Urruth; Bonan, Carla Denise; Barreto-Chaves, Maria Luiza M; Dalmaz, Carla; Sarkis, João José Freitas

2006-02-28

Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex

PubMed Central

Studholme, Colin; Frias, Antonio E.

2017-01-01

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci. SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders. PMID:28069920

Resting-state Functional Magnetic Resonance Imaging Analysis of Brain Functional Activity in Rats with Ischemic Stroke Treated by Electro-acupuncture.

PubMed

Liang, Shengxiang; Lin, Yunjiao; Lin, Bingbing; Li, Jianhong; Liu, Weilin; Chen, Lidian; Zhao, Shujun; Tao, Jing

2017-09-01

To evaluate whether electro-acupuncture (EA) treatment at acupoints of Zusanli (ST 36) and Quchi (LI 11) could reduce motor impairments and enhance brain functional recovery in rats with ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was established. EA at ST 36 and LI 11was started at 24 hours (MCAO + EA group) after ischemic stroke. The nontreatment (MCAO) and sham-operated control (SC) groups were included as controls. The neurologic deficits of all groups were assessed by Zea Longa scores and the modified neurologic severity scores on 24 hours and 8 days after MCAO. To further investigate the effect of EA on infract volume and brain function, magnetic resonance imaging was used to estimate the brain lesion and brain neural activities of each group at 8 days after ischemic stroke. Within 1 week after EA treatment, the neurologic deficits were significantly alleviated, and the cerebral infarctions were improved, including visual cortex, motor cortex, striatum, dorsal thalamus, and hippocampus. Furthermore, whole brain neural activities of auditory cortex, lateral nucleus group of dorsal thalamus, hippocampus, motor cortex, orbital cortex, sensory cortex, and striatum were decreased in MCAO group, whereas that of brain neural activities were increased after EA treatment, suggesting these brain regions are in accordance with the brain structure analysis. EA at ST 36 and LI 11 could enhance the neural activity of motor function-related brain regions, including motor cortex, dorsal thalamus, and striatum in rats, which is a potential treatment for ischemia stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Hyperlexia and ambient echolalia in a case of cerebral infarction of the left anterior cingulate cortex and corpus callosum.

PubMed

Suzuki, Tadashi; Itoh, Shouichi; Hayashi, Mototaka; Kouno, Masako; Takeda, Katsuhiko

2009-10-01

We report the case of a 69-year-old woman with cerebral infarction in the left anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a distinctive reading phenomenon, as well as ambient echolalia. Clinical features also included complex disorders such as visual groping, compulsive manipulation of tools, and callosal disconnection syndrome. She read words written on the cover of a book and repeated words emanating from unrelated conversations around her or from hospital announcements. The combination of these two features due to a focal lesion has never been reported previously. The supplementary motor area may control the execution of established subroutines according to external and internal inputs. Hyperlexia as well as the compulsive manipulation of tools could be interpreted as faulty inhibition of preexisting essentially intact motor subroutines by damage to the anterior cingulate cortex reciprocally interconnected with the supplementary motor area.

The "handwriting brain": a meta-analysis of neuroimaging studies of motor versus orthographic processes.

PubMed

Planton, Samuel; Jucla, Mélanie; Roux, Franck-Emmanuel; Démonet, Jean-François

2013-01-01

Handwriting is a modality of language production whose cerebral substrates remain poorly known although the existence of specific regions is postulated. The description of brain damaged patients with agraphia and, more recently, several neuroimaging studies suggest the involvement of different brain regions. However, results vary with the methodological choices made and may not always discriminate between "writing-specific" and motor or linguistic processes shared with other abilities. We used the "Activation Likelihood Estimate" (ALE) meta-analytical method to identify the cerebral network of areas commonly activated during handwriting in 18 neuroimaging studies published in the literature. Included contrasts were also classified according to the control tasks used, whether non-specific motor/output-control or linguistic/input-control. These data were included in two secondary meta-analyses in order to reveal the functional role of the different areas of this network. An extensive, mainly left-hemisphere network of 12 cortical and sub-cortical areas was obtained; three of which were considered as primarily writing-specific (left superior frontal sulcus/middle frontal gyrus area, left intraparietal sulcus/superior parietal area, right cerebellum) while others related rather to non-specific motor (primary motor and sensorimotor cortex, supplementary motor area, thalamus and putamen) or linguistic processes (ventral premotor cortex, posterior/inferior temporal cortex). This meta-analysis provides a description of the cerebral network of handwriting as revealed by various types of neuroimaging experiments and confirms the crucial involvement of the left frontal and superior parietal regions. These findings provide new insights into cognitive processes involved in handwriting and their cerebral substrates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

PubMed

Lenzi, Juliana; Rodrigues, Andre Felipe; Rós, Adriana de Sousa; de Castro, Amanda Blanski; de Castro, Bianca Blanski; de Lima, Daniela Delwing; Magro, Débora Delwing Dal; Zeni, Ana Lúcia Bertarello

2015-12-01

Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons.

PubMed

Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta; Weikop, Pia; Rath, Martin Fredensborg

2018-02-01

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Research on acupuncture points and cortical functional activation position in cats by infrared imaging detection

NASA Astrophysics Data System (ADS)

Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming

2007-12-01

The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.

Oxidative stress and cell death in the cerebral cortex as a long-term consequence of neonatal hypoglycemia.

PubMed

Anju, T R; Akhilraj, P R; Paulose, C S

2016-09-01

Neonatal hypoglycemia limits glucose supply to cells leading to long-term consequences in brain function. The present study evaluated antioxidant and cell death factors' alterations in cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Gene expression studies by real-time PCR were carried out using gene-specific TaqMan probes. Fluorescent dyes were used for immunohistochemistry and nuclear staining and imaged by confocal microscope. Total antioxidant level and expression of antioxidant enzymes - superoxide dismutase (SOD) and gluthathione peroxide (GPx) - mRNA was significantly reduced along with high peroxide level in the cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Real-time PCR analysis showed an upregulation of Bax, caspase 3, and caspase 8 gene expression. Confocal imaging with TOPRO-3 staining and immunohistochemistry with caspase 3 antibody indicated cell death activation. The reduced free radical scavenging capability coupled with the expression of key factors involved in cell death pathway points to the possibility of oxidative stress in the cortex of 1-month-old rats exposed to neonatal hypoglycemia. The observed results indicate the effects of neonatal hypoglycemia in determining the antioxidant capability of cerebral cortex in a later stage of life.

Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

PubMed

Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

2016-03-01

Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

PubMed

Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

2016-08-01

Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds.

Bipolar electrocoagulation on cortex after AVMs lesionectomy for seizure control.

PubMed

Cao, Yong; Wang, Rong; Yang, Lijun; Bai, Qin; Wang, Shuo; Zhao, Jizong

2011-01-01

The findings of previous studies remain controversial on the optimal management required for effective seizure control after surgical excision of arteriovenous malformations (AVMs). We evaluated the efficacy of additional bipolar electrocoagulation on the electrically positive cortex guided by intraoperative electrocorticography (ECoG) for controlling cerebral AVMs-related epilepsy. Sixty consecutive patients with seizure due to cerebral AVMs, who underwent surgical excision of cerebral AVMs and intraoperative ECoG, were assessed. The AVMs and surrounding hemosiderin stained tissue were completely removed, and bipolar electrocoagulation was applied on the surrounding cerebral cortex where epileptic discharges were monitored via intraoperative ECoG. Patients were followed up at three to six months after the surgery and then annually. We evaluated seizure outcome by using Engel's classification and postoperative complications. Forty-nine patients (81.6%) were detected of epileptic discharges before and after AVMs excision. These patients underwent the removal of AVMs plus bipolar electrocoagulation on spike-positive site cortex. After electrocoagulation, 45 patients' epileptic discharges disappeared, while four obviously diminished. Fifty-five of 60 patients (91.7%) had follow-up lasting at least 22 months (mean 51.1 months; range 22-93 months). Determined by the Engel Seizure Outcome Scale, 39 patients (70.9%) were Class I, seven (12.7%) Class II, five (9.0%) Class III, and four (7.2%) Class IV. Even after the complete removal of AVM and surrounding gliotic and hemosiderin stained tissue, a high-frequency residual spike remained on the surrounding cerebral cortex. Effective surgical seizure control can be achieved by carrying out additional bipolar electrocoagulation on the cortex guided by the intraoperative ECoG.

Comparison of gray matter volume and thickness for analysis of cortical changes in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Liu, Jiachao; Li, Ziyi; Chen, Kewei; Yao, Li; Wang, Zhiqun; Li, Kunchen; Guo, Xiaojuan

2011-03-01

Gray matter volume and cortical thickness are two indices of concern in brain structure magnetic resonance imaging research. Gray matter volume reflects mixed-measurement information of cerebral cortex, while cortical thickness reflects only the information of distance between inner surface and outer surface of cerebral cortex. Using Scaled Subprofile Modeling based on Principal Component Analysis (SSM_PCA) and Pearson's Correlation Analysis, this study further provided quantitative comparisons and depicted both global relevance and local relevance to comprehensively investigate morphometrical abnormalities in cerebral cortex in Alzheimer's disease (AD). Thirteen patients with AD and thirteen age- and gender-matched healthy controls were included in this study. Results showed that factor scores from the first 8 principal components accounted for ~53.38% of the total variance for gray matter volume, and ~50.18% for cortical thickness. Factor scores from the fifth principal component showed significant correlation. In addition, gray matter voxel-based volume was closely related to cortical thickness alterations in most cortical cortex, especially, in some typical abnormal brain regions such as insula and the parahippocampal gyrus in AD. These findings suggest that these two measurements are effective indices for understanding the neuropathology in AD. Studies using both gray matter volume and cortical thickness can separate the causes of the discrepancy, provide complementary information and carry out a comprehensive description of the morphological changes of brain structure.

Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

PubMed

Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

2014-04-01

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

Effect of oral administration of Pheretima aspergillum (earthworm) in rats with cerebral infarction induced by middle-cerebral artery occlusion.

PubMed

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Huang, Chih-Yang; Hsieh, Ching-Liang

2012-01-01

We investigated the curative effect of Pheretima aspergillum (earthworm, PA) on rats with middle cerebral artery occlusion (MCAo). The MCAo-induced cerebral infarction was established and its underlying mechanisms by counting the infarction areas and evaluating the rats' neurological status. Immunostaining was used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B, and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that oral administration of PA for two weeks to rats with MCAo successfully reduced cerebral infarction areas in the cortex and striatum, and also reduced scores of neurological deficit. The PA-treated MCAo rats showed greatly decreased neuronal death, glial proliferation, and S100B proteins in the penumbra area of the cortex and in the ischemic core area of the cortex, but BDNF did not changed. These results demonstrated novel and detailed cellular mechanisms underlying the neuroprotective effects of PA in MCAo rats.

Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

PubMed Central

Winter, Mark R.; Liu, Mo; Monteleone, David; Melunis, Justin; Hershberg, Uri; Goderie, Susan K.; Temple, Sally; Cohen, Andrew R.

2015-01-01

Summary Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex. PMID:26344906

Neural Correlates of Suicidal Ideation and Its Reduction in Depression

PubMed Central

Lally, Níall; Nugent, Allison C.; Furey, Maura L.; Luckenbaugh, David A.; Zarate, Carlos A.

2015-01-01

Background: The neural correlates of suicidal ideation and its reduction after treatment are unknown. We hypothesized that increased regional cerebral glucose metabolism in the infralimbic cortex (Brodmann area 25), amygdala, and subgenual anterior cingulate cortex would be associated with suicidal ideation and its reduction after ketamine infusion. Methods: Medication-free patients (n=19) with treatment-resistant major depressive disorder underwent positron emission tomography imaging at baseline and 230 minutes after an open-label ketamine infusion (0.5mg/kg for 40 minutes). Results: Baseline suicidal ideation and regional cerebral glucose metabolism in the infralimbic cortex were significantly correlated (r=.59, P=.007); but not overall mood scores (r=−.07, P=.79). Reductions in suicidal ideation after ketamine infusion were correlated with decreased regional cerebral glucose metabolism in the infralimbic cortex (r=.54, P=.02). Metabolism in other areas of interest was not significantly correlated with suicidal ideation or depression. Conclusion: The infralimbic cortex may be implicated in suicidal ideation. PMID:25550331

Role of the Functional State of the Hypothalamus in Bioelectric Reactions of the Cerebral Cortex to Radiation,

DTIC Science & Technology

The effect of subjection of the hypothalamus to electrocoagulation in the area of the mamillary bodies on the bioelectric activity and reactivity of...the cerebral cortex exposed to radiation was studied. Rabbits were irradiated on the 10th day after electrocoagulation . Immediately after... electrocoagulation , a decline in the excitability and functional activity of cortical neurons in the posterior section of the cortex and a decrease in the

Role of Hydrogen Sulfide in Early Blood-Brain Barrier Disruption following Transient Focal Cerebral Ischemia

PubMed Central

Jiang, Zheng; Li, Chun; Manuel, Morganne L.; Yuan, Shuai; Kevil, Christopher G.; McCarter, Kimberly D.; Lu, Wei; Sun, Hong

2015-01-01

We determined the role of endogenous hydrogen sulfide (H₂S) in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Regional vascular response and cerebral blood flow (CBF) during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE)) and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST)), but not O-(Carboxymethyl)hydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS)), abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/-) reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn’t further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S) production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia. PMID:25695633

In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the Developing Cerebral Cortex

PubMed Central

Azzarelli, Roberta; Oleari, Roberto; Lettieri, Antonella; Andre', Valentina; Cariboni, Anna

2017-01-01

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration. PMID:28448448

Annual Research Review: Development of the Cerebral Cortex--Implications for Neurodevelopmental Disorders

ERIC Educational Resources Information Center

Rubenstein, John L. R.

2011-01-01

The cerebral cortex has a central role in cognitive and emotional processing. As such, understanding the mechanisms that govern its development and function will be central to understanding the bases of severe neuropsychiatric disorders, particularly those that first appear in childhood. In this review, I highlight recent progress in elucidating…

Sex Difference in Daily Rhythms of Clock Gene Expression in the Aged Human Cerebral Cortex

PubMed Central

Lim, Andrew S.P.; Myers, Amanda J.; Yu, Lei; Buchman, Aron S.; Duffy, Jeanne F.; De Jager, Philip L.; Bennett, David A.

2013-01-01

Background Studies using self-report and physiological markers of circadian rhythmicity have demonstrated sex differences in a number of circadian attributes including morningness-eveningness, entrained phase, and intrinsic period. However, these sex differences have not been examined at the level of the molecular clock, and not in human cerebral cortex. We tested the hypothesis that there are detectable daily rhythms of clock gene expression in human cerebral cortex, and that there are significant sex differences in the timing of these rhythms. Methods We quantified the expression levels of three clock genes – PER2, PER3, and ARNTL1 in samples of dorsolateral prefrontal cortex from 490 deceased individuals in two cohort studies of older individuals, the Religious Orders Study and the Rush Memory and Aging Project, using mRNA microarray data. We parameterized clock gene expression at death as a function of time of death using cosine curves, and examined for sex differences in the phase of these curves. Findings Significant daily variation was seen in the expression of PER2 (p=0.004), PER3 (p=0.003) and ARNTL1 (p=0.0005). PER2/3 expression peaked at 10:38 [95%CI 9:20–11:56] and 10:44 [95%CI 9:29–11:59] respectively, and ARNTL1 expression peaked in antiphase to this at 21:23 [95%CI 20:16–22:30]. The timing of the expression of all three genes was significantly earlier in women than in men (PER2 6.8 hours p=0.002; PER3 5.5 hours p=0.001; ARNTL1 4.7 hours p=0.007). Interpretation Daily rhythms of clock gene expression are present in human cerebral cortex and can be inferred from postmortem samples. Moreover, these rhythms are relatively delayed in men compared to women. PMID:23606611

Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

PubMed

Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

2016-08-01

Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse.

PubMed

Cramer, Samuel W; Popa, Laurentiu S; Carter, Russell E; Chen, Gang; Ebner, Timothy J

2015-04-08

The Ca(2+) channelopathies caused by mutations of the CACNA1A gene that encodes the pore-forming subunit of the human Cav2.1 (P/Q-type) voltage-gated Ca(2+) channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric abnormalities involving the cerebral cortex. This study demonstrates episodic, low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering (tg/tg) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the LFOs in tg/tg mice can spontaneously develop very high power, referred to as a high-power state. The LFOs in tg/tg mice are mediated in part by neuronal activity as tetrodotoxin decreases the oscillations and cortical neuron discharge contain the same low frequencies. The high-power state involves compensatory mechanisms because acutely decreasing P/Q-type Ca(2+) channel function in either wild-type (WT) or tg/tg mice does not induce the high-power state. In contrast, blocking l-type Ca(2+) channels, known to be upregulated in tg/tg mice, reduces the high-power state. Intriguingly, basal excitatory glutamatergic neurotransmission constrains the high-power state because blocking ionotropic or metabotropic glutamate receptors results in high-power LFOs in tg/tg but not WT mice. The high-power LFOs are decreased markedly by acetazolamide and 4-aminopyridine, the primary treatments for EA2, suggesting disease relevance. Together, these results demonstrate that the high-power LFOs in the tg/tg cerebral cortex represent a highly abnormal excitability state that may underlie noncerebellar symptoms that characterize CACNA1A mutations. Copyright © 2015 the authors 0270-6474/15/355664-16$15.00/0.

Cortical Proteins are Chemokinetic to Cells from the Medial Ganglionic Eminence

DTIC Science & Technology

2011-05-28

et al., 2009). Disruption of interneuron migration can lead to improper distribution within the cortex and is associated with schizophrenia, autism ...include the neurotrophins; the growth factors NRG1 and GDNF, the chemokine, SDF-1 and neurotransmitters, glutamate, GABA, and dopamine (Stumm et al...Bhide PG ( Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci 27:3813-3822.2007

‘Inner voices’: the cerebral representation of emotional voice cues described in literary texts

PubMed Central

Kreifelts, Benjamin; Gößling-Arnold, Christina; Wertheimer, Jürgen; Wildgruber, Dirk

2014-01-01

While non-verbal affective voice cues are generally recognized as a crucial behavioral guide in any day-to-day conversation their role as a powerful source of information may extend well beyond close-up personal interactions and include other modes of communication such as written discourse or literature as well. Building on the assumption that similarities between the different ‘modes’ of voice cues may not only be limited to their functional role but may also include cerebral mechanisms engaged in the decoding process, the present functional magnetic resonance imaging study aimed at exploring brain responses associated with processing emotional voice signals described in literary texts. Emphasis was placed on evaluating ‘voice’ sensitive as well as task- and emotion-related modulations of brain activation frequently associated with the decoding of acoustic vocal cues. Obtained findings suggest that several similarities emerge with respect to the perception of acoustic voice signals: results identify the superior temporal, lateral and medial frontal cortex as well as the posterior cingulate cortex and cerebellum to contribute to the decoding process, with similarities to acoustic voice perception reflected in a ‘voice’-cue preference of temporal voice areas as well as an emotion-related modulation of the medial frontal cortex and a task-modulated response of the lateral frontal cortex. PMID:24396008

Effect of allo- and xenotransplantation of embryonic nervous tissue and umbilical cord blood-derived stem cells on structural and functional state of cerebral cortex of albino rats in posttraumatic period.

PubMed

Ereniev, S I; Semchenko, V V; Sysheva, E V; Bogdashin, I V; Shapovalova, V V; Khizhnyak, A S; Gasanenko, L N

2005-11-01

Comparative study of the structural and functional state of cerebral cortex of adult albino rats after intracerebral allo- and xenotransplantation of embryonic nervous tissue and intravenous injection of umbilical cord blood-derived stem cells at different terms after diffuse-focal cerebral trauma revealed the best cerebroprotective effect on day 7 of posttraumatic period in animals receiving embryonic nervous tissue.

Microvasculature of the cerebral cortex: a vascular corrosion cast and immunocytochemical study.

PubMed

Scala, Gaetano

2014-04-01

In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays important roles in the physiological and pathological processes of the brain. The aim of the present work is to analyze the CCM by use of the SEM-vascular corrosion cast technique, and to examine the immunocytochemical characteristics of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the SEM-immunogold technique. The CCM originated from the very small, finger-like terminal branches of the macrovasculature of the brain. The superficial cortical arterioles were more numerous than the deep straight arterioles which proceeded toward the white matter. The surface casts of the arterioles and capillaries of the cerebral cortex showed ring-shaped formations in the arterioles and at the origin of the capillaries. All capillaries down-stream from these ring-shaped formations were flaccid. Casts of the capillaries showed wrinkles due to the presence of endothelial folds, which is characteristic of varying blood pressure. Formations having intense anti-GIFAP immunoreactivity were frequently evident along the course of the blood capillaries in the cerebral cortex. These formations were probably astrocytes that might regulate the cerebral microcirculation based on physiological and pathological stimuli, such as neuronal activation. Copyright © 2014 Wiley Periodicals, Inc.

Age related rise in lactate and its correlation with lactate dehydrogenase (LDH) status in post-mitochondrial fractions isolated from different regions of brain in mice.

PubMed

Datta, Siddhartha; Chakrabarti, Nilkanta

2018-04-18

Rise in brain lactate is the hallmark of ageing. Separate studies report that ageing is associated with elevation of lactate level and alterations of lactate dehydrogenase (LDH)-A/B mRNA-expression-ratio in cerebral cortex and hippocampus. However, age related lactate rise in brain and its association with LDH status and their brain regional variations are still elusive. In the present study, level of lactate, LDH (A and B) activity and LDH-A expression were evaluated in post-mitochondrial fraction of tissues isolated from four different brain regions (cerebral cortex, hippocampus, substantia nigra and cerebellum) of young and aged mice. Lactate levels elevated in four brain regions with maximum rise in substantia nigra of aged mice. LDH-A protein expression and its activity decreased in cerebral cortex, hippocampus and substantia nigra without any changes of these parameters in cerebellum of aged mice. LDH-B activity decreased in hippocampus, substantia nigra and cerebellum whereas its activity remains unaltered in cerebral cortex of aged mice. Accordingly, the ratio of LDH-A/LDH-B-activity remains unaltered in hippocampus and substantia nigra, decreased in cerebral cortex and increased in cerebellum. Therefore, rise of lactate in three brain regions (cerebral cortex, hippocampus, substantia nigra) appeared to be not correlated with the alterations of its regulatory enzymes activities in these three brain regions, rather it supports the fact of involvement of other mechanisms, like lactate transport and/or aerobic/anaerobic metabolism as the possible cause(s) of lactate rise in these three brain regions. The increase in LDH-A/LDH-B-activity-ratio appeared to be positively correlated with elevated lactate level in cerebellum of aged mice. Overall, the present study indicates that the mechanism of rise in lactate in brain varies with brain regions where LDH status plays an important role during ageing. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Raman spectra of monkey cerebral cortex tissue].

PubMed

Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

2010-01-01

Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

Local cerebral glucose utilization during status epilepticus in newborn primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.

1989-06-01

The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc inmore » frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.« less

Effects of hypothermia and cerebral ischemia on cold-inducible RNA-binding protein mRNA expression in rat brain.

PubMed

Liu, Aijun; Zhang, Zhiwen; Li, Anmin; Xue, Jinghui

2010-08-06

CIRP (cold-inducible RNA-binding protein) mRNA is highly expressed in hypothermic conditions in mammalian cells, and the relationship between CIRP and neuroprotection for cerebral ischemia under hypothermia has been focused upon. At present, however, the expression characteristics of CIRP under hypothermia and cerebral ischemia in vivo are not clearly elucidated. In this study, CIRP mRNA expression in various regions of rat brain was examined by reverse transcriptase polymerase chain reaction (RT-PCR). CIRP expression levels were found to be similar in the hippocampus and cortex. Real-time quantitative PCR analysis revealed increasing CIRP mRNA expression in the cortex during the 24-h observation period following treatment with hypothermia or cerebral ischemia, with a greater increase in the hypothermia group. When cerebral ischemia was induced following hypothermia, CIRP mRNA expression in the cortex again showed a significant increasing tendency, but ischemia delayed the appearance of this increase. To reveal the relationship between CIRP and energy metabolism in the rat brain, lactate and pyruvate concentrations in the cortex of the rats treated with hypothermia, ischemia and ischemia after hypothermia were determined by spectrophotometric assay, and levels of phosphofructokinas-1 (PFK-1), the major regulatory enzyme of the glycolytic pathway, in the rat cortex in the three groups was also analyzed by Western blot. Using linear correlation, lactate and pyruvate concentrations, and PFK-1 levels, were each analyzed in the three groups in association with CIRP mRNA expression levels. The analysis did not reveal any correlation between the three metabolic parameters and CIRP mRNA expression induced by hypothermia, suggesting that while playing a role in neuroprotection under hypothermia, CIRP does not affect cerebral energy metabolism. Copyright 2010. Published by Elsevier B.V.

Research on relation between cortical functional section and acupuncture point

NASA Astrophysics Data System (ADS)

Chen, Shuwang; Li, Chunhua; Liang, Guozhuang; Wang, Shuhai

2008-02-01

The application of the infrared imaging using in the brain cognition and the acupuncture is introduced. Acupuncturing a certain point of the healthy experimental cats, observing the responds of the cerebral cortical temperature by using of infrared imaging, and researching the corresponding relation between the acupuncture points with the active sections of the cerebral cortex, so the effect of the acupuncture is obtained. The theory of the refreshment and induce resuscitation pinprick is approved. The method of the "refreshment and induce resuscitation pinprick" can promote the metabolize renovation, improve the living function and increase the healing rate. However, the relations between the points and the cortical functional sections have not the last word still. After removing the skulls on the head, full of the cerebral cortex of a cat are exposed. Observing the infrared imaging and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing the points to judge the activation position. During the process of acupuncture, the trend of the rising temperature on cerebral cortex is primary in terms of the phenomena in the infrared pictures. The cortical hemogram variety is measured in terms of the infrared pictures and the temperature values, so the characteristic curve of the temperature for a corresponding position on the cerebral cortex and the acupuncture point can be obtained. When the acupuncture point is changed, the position where temperature varied on cerebral cortex is different correspondingly. The variety in the cortical functional sections is corresponding to the result of the acupuncture point in terms of the imaging and the temperatures. The experimental results accord with the theoretic model, so they validate the correctness of the "refreshment and induce resuscitation pinprick". According to the experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly. The similar relations can be applied in human being in terms of the comparative acupuncture. The conclusions of the research can provide the evidences in the infrared pictures and the temperature values for the studies on the acupuncture applied in the field of brain cognition.

A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex.

PubMed

Reillo, Isabel; de Juan Romero, Camino; García-Cabezas, Miguel Ángel; Borrell, Víctor

2011-07-01

The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.

Cellular scaling rules for the brain of afrotherians

PubMed Central

Neves, Kleber; Ferreira, Fernanda M.; Tovar-Moll, Fernanda; Gravett, Nadine; Bennett, Nigel C.; Kaswera, Consolate; Gilissen, Emmanuel; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate and eulipotyphlan brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in evolution in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of afrotherians, believed to be the first clade to radiate from the common eutherian ancestor. We find that afrotherians share non-neuronal scaling rules with rodents, primates and eulipotyphlans, as well as the coordinated scaling of numbers of neurons in the cerebral cortex and cerebellum. Afrotherians share with rodents and eulipotyphlans, but not with primates, the scaling of number of neurons in the cortex and in the cerebellum as a function of the number of neurons in the rest of the brain. Afrotheria also share with rodents and eulipotyphlans the neuronal scaling rules that apply to the cerebral cortex. Afrotherians share with rodents, but not with eulipotyphlans nor primates, the neuronal scaling rules that apply to the cerebellum. Importantly, the scaling of the folding index of the cerebral cortex with the number of neurons in the cerebral cortex is not shared by either afrotherians, rodents, or primates. The sharing of some neuronal scaling rules between afrotherians and rodents, and of some additional features with eulipotyphlans and primates, raise the interesting possibility that these shared characteristics applied to the common eutherian ancestor. In turn, the clade-specific characteristics that relate to the distribution of neurons along the surface of the cerebral cortex and to its degree of gyrification suggest that these characteristics compose an evolutionarily plastic suite of features that may have defined and distinguished mammalian groups in evolution. PMID:24596544

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

PubMed

Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

2015-01-01

Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar

Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex formore » each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.« less

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

PubMed Central

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Conclusions Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions. PMID:25993263

TH-EF-BRB-01: BEST IN PHYSICS (THERAPY): Dosimetric Comparison of 4π and Clinical IMRT for Cortex-Sparing High-Grade Glioma Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, K; Tran, A; Yu, V

Purpose: Thinning of the cerebral cortex has been observed in patients treated with fractionated partial brain radiation therapy and may contribute to cognitive decline following treatment. The extent of this thinning is dose-dependent, and was shown comparable to that of neurodegenerative diseases such as Alzheimer’s disease at one year post-therapy. This study investigates whether 4π radiotherapy can enable better sparing of the cortex and other critical structures when compared to conventional clinical IMRT plans. Methods: Clinical cortex-sparing IMRT plans for 15 high-grade glioma patients were included in this study. 4π radiotherapy plans were created for each patient with 20 intensity-modulatedmore » non-coplanar fields selected with a greedy column-generation optimization. All plans were normalized to deliver 100% of the prescribed dose to 95% of the planning target volume (PTV). The mean and maximum dose to the cerebral cortex and other organs at risk (OARs) were compared for the two plan types, as well as the conformity index (CI), homogeneity index (HI), and 50% dose spillage volume (R50). Results: The 4π plans significantly reduced the mean cortex dose by an average of 16% (range 6% to 27%) compared to the clinical plans. The mean dose to every other OAR compared was also reduced by 15% to 43%, with statistically significant reductions to the brainstem, chiasm, eyes, optic nerves, subcortical whit, and hippocampus. The average maximum doses were also reduced for 10/12 OARs. The R50 was significantly reduced with the 4π plans (>14%) and the homogeneity index was significantly improved. Conclusion: 4π enables significant sparing of the cerebral cortex when treating high-grade gliomas with fractionated partial brain radiation therapy, potentially reducing the risk of harmful dose-dependent cortical thinning. NIH R43CA183390, NIH R01CA188300, Varian Medical Systems.« less

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

PubMed

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

NASA Astrophysics Data System (ADS)

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

PubMed

Wisor, J P; Morairty, S R; Huynh, N T; Steininger, T L; Kilduff, T S

2006-08-11

Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

Vygotsky Meets Neuroscience: The Cerebellum and the Rise of Culture through Play

ERIC Educational Resources Information Center

Vandervert, Larry

2017-01-01

The author suggests the brain's cerebellum and cerebral cortex are the origin of culture and considers the cerebellar models that came to constitute culture to be derived specifically from play. He summarizes recent research on the behavioral, cognitive, and affective evolution of the cerebellum and the cerebral cortex that shows the development…

The capillary bed offers the largest hemodynamic resistance to the cortical blood supply

PubMed Central

Gould, Ian Gopal; Tsai, Philbert; Kleinfeld, David

2016-01-01

The cortical angioarchitecture is a key factor in controlling cerebral blood flow and oxygen metabolism. Difficulties in imaging the complex microanatomy of the cortex have so far restricted insight about blood flow distribution in the microcirculation. A new methodology combining advanced microscopy data with large scale hemodynamic simulations enabled us to quantify the effect of the angioarchitecture on the cerebral microcirculation. High-resolution images of the mouse primary somatosensory cortex were input into with a comprehensive computational model of cerebral perfusion and oxygen supply ranging from the pial vessels to individual brain cells. Simulations of blood flow, hematocrit and oxygen tension show that the wide variation of hemodynamic states in the tortuous, randomly organized capillary bed is responsible for relatively uniform cortical tissue perfusion and oxygenation. Computational analysis of microcirculatory blood flow and pressure drops further indicates that the capillary bed, including capillaries adjacent to feeding arterioles (d < 10 µm), are the largest contributors to hydraulic resistance. PMID:27780904

Changes in the brain biogenic monoamines of rats, induced by piracetam and aniracetam.

PubMed

Petkov, V D; Grahovska, T; Petkov, V V; Konstantinova, E; Stancheva, S

1984-01-01

Single oral dose of 600 mg/kg weight piracetam, respectively 50 mg/kg aniracetam, causes essential changes in the level and turnover of dopamine (DA) and serotonin (5-HT) in some rat cerebral structures. When the animals were killed one hour after the administration of the drugs, piracetam significantly increased the DA level in the cerebral cortex and in the striatum, as well as the 5-HT level in the cortex, reducing the 5-HT level in the striatum, brain stem and hypothalamus. At the same time, under the effect of piracetam the DA turnover was accelerated in the cortex and hypothalamus and delayed in the striatum, the noradrenaline turnover was accelerated in the brain stem, the 5-HT turnover was accelerated in the cortex and delayed in the striatum, stem and hypothalamus. Under the effect of aniracetam the DA level was reduced in the striatum and hypothalamus; the 5-HT level was also decreased in the hypothalamus and increased in the cortex and striatum. Aniracetam delayed the DA turnover in the striatum and the 5-HT turnover in the hypothalamus, accelerating the 5-HT turnover in the cortex, striatum and stem. The results obtained show that the changes induced in the cerebral biogenic monoamines participate in the mechanism of action of piracetam and aniracetam, whereby it seems that the analogies and differences in their effects on the cerebral biogenic monoamines play a definite role for the observed analogies and differences in the behavioural effects of these two "nootropic" compounds.

Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices.

PubMed

Torres, I L; Gamaro, G D; Silveira-Cucco, S N; Michalowski, M B; Corrêa, J B; Perry, M L; Dalmaz, C

2001-01-01

It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 microCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

Intrathecal baclofen treatment in dystonic cerebral palsy: a randomized clinical trial: the IDYS trial

PubMed Central

2013-01-01

Background Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. Methods/Design A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics influence outcome. Discussion The results of this study will provide data for evidence-based use of intrathecal baclofen in dystonic cerebral palsy. Trial registration Nederlands Trial Register, NTR3642 PMID:24165282

Localizing the Frequency x Regularity Word Reading Interaction in the Cerebral Cortex

ERIC Educational Resources Information Center

Cummine, Jacqueline; Sarty, Gordon E.; Borowsky, Ron

2010-01-01

The aim of this work is to combine behavioural and functional magnetic resonance imaging (fMRI) data to advance our knowledge of where the Frequency x Regularity interaction on word naming is located in the cerebral cortex. Participants named high and low frequency, regular and exception words in a behavioural lab (Experiment 1) and during an fMRI…

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuriya, Mutsuo; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This primingmore » effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. - Highlights: • Background NE augments the responsiveness of astrocytes to subsequent NE stimulation. • The priming effect is independent of neuronal activity and mediated by βadrenoceptor. • Background subthreshold NE may play gliomodulatory roles in the cerebral cortex.« less

The elephant brain in numbers

PubMed Central

Herculano-Houzel, Suzana; Avelino-de-Souza, Kamilla; Neves, Kleber; Porfírio, Jairo; Messeder, Débora; Mattos Feijó, Larissa; Maldonado, José; Manger, Paul R.

2014-01-01

What explains the superior cognitive abilities of the human brain compared to other, larger brains? Here we investigate the possibility that the human brain has a larger number of neurons than even larger brains by determining the cellular composition of the brain of the African elephant. We find that the African elephant brain, which is about three times larger than the human brain, contains 257 billion (109) neurons, three times more than the average human brain; however, 97.5% of the neurons in the elephant brain (251 billion) are found in the cerebellum. This makes the elephant an outlier in regard to the number of cerebellar neurons compared to other mammals, which might be related to sensorimotor specializations. In contrast, the elephant cerebral cortex, which has twice the mass of the human cerebral cortex, holds only 5.6 billion neurons, about one third of the number of neurons found in the human cerebral cortex. This finding supports the hypothesis that the larger absolute number of neurons in the human cerebral cortex (but not in the whole brain) is correlated with the superior cognitive abilities of humans compared to elephants and other large-brained mammals. PMID:24971054

Maternal Geophagy of Calabash Chalk on Foetal Cerebral Cortex Histomorphology.

PubMed

Ekanem, Theresa Bassey; Ekong, Moses Bassey; Eluwa, Mokutima Amarachi; Igiri, Anozeng Oyono; Osim, Eme Efiom

2015-01-01

Calabash chalk, a kaolin-base substance is a common geophagic material mostly consumed by pregnant women. This study investigated its effect on the histomorphology of the foetal cerebral cortex. Twelve gestating Wistar rats were divided equally into groups 1 and 2. On pregnancy day seven (PD7), group 2 animals were administered 200 mg/kg body weight of calabash chalk suspension, while group 1 animals served as the control and received 1 ml of distilled water, by oral gavages and for 14 days (PD7-PD20). On PD21, the dams were sacrificed, and the foetuses removed, examined for gross malformations, weighed and culled to two foetuses per mother. Their whole brains were excised, weighed and preserved using 10% buffered formalin, and routinely processed by haematoxylin and eosin, and Luxol fast blue methods. The foetuses showed no morphological change, but their mean body weights was higher (p=0.0001). Histomorphological sections of the cerebral cortex showed hypertrophy and hyperplasia of cells in all the cortical layers, with less demonstrated Nissl and higher (p=0.001) cellular population compared with the control group. Calabash chalk cause body weight increase and histomorphological changes in the cerebral cortex of foetuses.

The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

PubMed Central

Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

2013-01-01

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID:24032005

Are you also what your mother eats? Distinct proteomic portrait as a result of maternal high-fat diet in the cerebral cortex of the adult mouse.

PubMed

Manousopoulou, A; Woo, J; Woelk, C H; Johnston, H E; Singhania, A; Hawkes, C; Garbis, S D; Carare, R O

2015-08-01

Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Our aim was to compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Male mice born to dams fed a control (C) or high-fat (H) diet 4 weeks before conception and during gestation, and lactation were assigned to either C or H diet at weaning. Mice were killed at 19 weeks and their cerebral cortices were analysed using a two-dimensional liquid chromatography-mass spectrometry methodology. In total, 6 695 proteins were identified (q<0.01), 10% of which were modulated in at least one of the groups relative to controls. In silico analysis revealed that mice clustered based on the diet of the mother and not their own diet and that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Maternal high-fat diet resulted in distinct endophenotypic changes of the adult offspring cerebral cortex independent of its current diet. The identified proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.

Hyperglycemia decreases expression of 14-3-3 proteins in an animal model of stroke.

PubMed

Jeon, Seong-Jun; Sung, Jin-Hee; Koh, Phil-Ok

2016-07-28

Diabetes is a severe metabolic disorder and a major risk factor for stroke. Stroke severity is worse in patients with diabetes compared to the non-diabetic population. The 14-3-3 proteins are a family of conserved acidic proteins that are ubiquitously expressed in cells and tissues. These proteins are involved in many cellular processes including metabolic pathways, signal transduction, protein trafficking, protein synthesis, and cell cycle control. This study investigated 14-3-3 proteins expression in the cerebral cortex of animals with diabetes, cerebral ischemic injury and a combination of both diabetes and cerebral ischemic injury. Diabetes was induced by intraperitoneal injection of streptozotocin (40mg/kg) in adult male rats. After 4 weeks of treatment, middle cerebral artery occlusion (MCAO) was performed for the induction of focal cerebral ischemia and cerebral cortex tissue was collected 24h after MCAO. We confirmed that diabetes increases infarct volume following MCAO compared to non-diabetic animals. In diabetic animals with MCAO injury, reduction of 14-3-3 β/α, 14-3-3 ζ/δ, 14-3-3 γ, and 14-3-3 ε isoforms was detected. The expression of these proteins was significantly decreased in diabetic animals with MCAO injury compared to diabetic-only and MCAO-only animals. Moreover, Western blot analysis ascertained the decreased expression of 14-3-3 family proteins in diabetic animals with MCAO injury, including β/α, ζ/δ, γ, ε, τ, and η isoforms. These results show the changes of 14-3-3 proteins expression in streptozotocin-induced diabetic animals with MCAO injury. Thus, these findings suggest that decreases in 14-3-3 proteins might be involved in the regulation of 14-3-3 proteins under the presence of diabetes following MCAO. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

CORRELATION INDICES OF CEREBRAL HEMODYNAMICS AND ELECTRICAL ACTIVITY IN CHILDREN WITH IMPAIRED MOTOR SKILLS.

PubMed

Golovchenko, I V; Hayday, M I

The correlations between the indicators of cerebral hemodynamics and electrical activity in children with impaired motor skills of central origin (children with cerebral palsy) were investigated. There is established a high number of links between indicators of rheoencephalogram (REG) and electroencephalogram (EEG) in the left cerebral hemisphere than in the right. In frontomastoidal allocation 19 correlations and in occipitomastoidal - 59 links. We suppose that poor circulation in vertebroplasty-basilar system leads to the defeat of the brain stem, which, with afferent pathways of the reticular formation, connects the thalamus with the cortex. In the reticular formation there is an inhibition of ascending activators influences, which eland to decreasing of the cortex is tonus. You can talk about the functional immaturity of the system of nonspecific activation by the reticular formation of the brain stem. Children with violation of motor activity had significantly more negative and positive significant and high correlation among the existing indicators of electric brain activity and cerebral hemodynamics, in our opinion, is due to the development of interconnection compensation that is carried out by adjustment of the functional systems and the formation of new forms of adaptive responses in conditions of disontogenetik. Feature correlation pattern of the EEG, of children with disorders of motor activity, is associated with a significantly great number of high and significant correlations between measures of electrical brain activity in the δ- and q- rhythms, especially in the temporal areas of the cerebral cortex. According to visual analysis of EEG there is revealed a common manifestation of changes of bioelectric brain activity in children with disorders of motor activity. This is manifested in the development of paroxysmal activity of action potentials of θ- and δ-rhythms with the focus of activity in the anterior areas of the cerebral cortex; the formation of a mosaic representation of the θ-rhythms in temporal areas; the presence of hypersynchronous a-paroxysms in the posterior areas of the cerebral cortex. The given facts testify to activation of mechanisms of limbic-neocortical systems and synchronizing influences of the reticular formation of the stem and diencephalic structures. There is also detected greater number of correlations when occipitomastoidal registration was lone it reflects compensatory redistribution of cerebral blood flow over the affected structures of brain stem structures that are associated with the provision of cortical functions.

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

[Effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water].

PubMed

Xiuwen, Yang; Hongchen, Liu; Ke, Li; Zhen, Jin; Gang, Liu

2014-12-01

We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water. Six male and female subjects were subjected to whole-brain fMRI during the phasic delivery of non-noxious hot (23 °C) and no- xious cold (4 °C) water intraoral stimulation. A block-design blood oxygenation level-dependent fMRI scan covering the entire brain was also carried out. The activated cortical areas were as follows: left pre-/post-central gyrus, insula/operculum, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), midbrain red nucleus, and thalamus. The activated cortical areas under cold condition were as follows: left occipital lobe, premotor cortex/Brodmann area (BA) 6, right motor language area BA44, lingual gyrus, parietal lobule (BA7, 40), and primary somatosensory cortex S I. Comparisons of the regional cerebral blood flow response magnitude were made among stereotactically concordant brain regions that showed significant responses under the two conditions of this study. Compared with non-noxious warmth, more regions were activated in noxious coldness, and the magnitude of activation in areas produced after non-noxious warm stimulation significantly increased. However, ACC only significantly increased the magnitude of activation under noxious coldness stimulation. Results suggested that a similar network of regions was activated common to the perception of pain and no-pain produced by either non-noxious warmth or noxious coldness stimulation. Non-noxious warmth also activated more brain regions and significantly increased the response magnitude of cerebral-cortex activation compared with noxious coldness. Noxious coldness stimulation further significantly increased the magnitude of activation in ACC areas compared with noxious warmth.

Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki-67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus.

PubMed

He, Jianlong; Ji, Xiaoying; Li, Yongfei; Xue, Xiaochang; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Gao, Meilii

2016-01-01

Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki-67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region-difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki-67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression. Copyright © 2015 Elsevier GmbH. All rights reserved.

Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer

PubMed Central

Yamazaki, Yukiko; Makino, Hatsune; Hamaguchi-Hamada, Kayoko; Hamada, Shun; Sugino, Hidehiko; Kawase, Eihachiro; Miyata, Takaki; Ogawa, Masaharu; Yanagimachi, Ryuzo; Yagi, Takeshi

2001-01-01

When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5–17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells. PMID:11698647

Effect of electroacupuncture on the expression of interlukin-1beta mRNA after transient focal cerebral ischemia.

PubMed

Xu, Zhen-Feng; Wu, Gen-Cheng; Cao, Xiao-Ding

2002-01-01

It has been reported that interleukin-1beta (IL-1beta ) play a key role in the pathogenesis of cerebral ischemia. Acupuncture is an effective traditional medical therapy in China. The aim of present study was to evaluate the effect of electroacupuncture (EA) on IL-1beta mRNA expression after middle cerebral artery occlusion (MCAO) in rats. Using in situ hybridization technique, it was found that in the MCAO group the expression of IL-1beta mRNA was significantly increased at 2h, 6h, 12h after reperfusion in cerebral ischemic cortex compared with normal group. In EA+ MCAO group the expression of IL-1beta mRNA was significantly decreased at 2h, 6h and 12h in ischemic cortex compared with MCAO group. The results indicated that EA might decrease the IL-1beta protein expression by reducing the IL-beta mRNA expression in ischemic cortex.

In Vivo Imaging of Flavoprotein Fluorescence During Hypoxia Reveals the Importance of Direct Arterial Oxygen Supply to Cerebral Cortex Tissue.

PubMed

Chisholm, K I; Ida, K K; Davies, A L; Papkovsky, D B; Singer, M; Dyson, A; Tachtsidis, I; Duchen, M R; Smith, K J

2016-01-01

Live imaging of mitochondrial function is crucial to understand the important role played by these organelles in a wide range of diseases. The mitochondrial redox potential is a particularly informative measure of mitochondrial function, and can be monitored using the endogenous green fluorescence of oxidized mitochondrial flavoproteins. Here, we have observed flavoprotein fluorescence in the exposed murine cerebral cortex in vivo using confocal imaging; the mitochondrial origin of the signal was confirmed using agents known to manipulate mitochondrial redox potential. The effects of cerebral oxygenation on flavoprotein fluorescence were determined by manipulating the inspired oxygen concentration. We report that flavoprotein fluorescence is sensitive to reductions in cortical oxygenation, such that reductions in inspired oxygen resulted in loss of flavoprotein fluorescence with the exception of a preserved 'halo' of signal in periarterial regions. The findings are consistent with reports that arteries play an important role in supplying oxygen directly to tissue in the cerebral cortex, maintaining mitochondrial function.

Computerized mappings of the cerebral cortex: a multiresolution flattening method and a surface-based coordinate system

NASA Technical Reports Server (NTRS)

Drury, H. A.; Van Essen, D. C.; Anderson, C. H.; Lee, C. W.; Coogan, T. A.; Lewis, J. W.

1996-01-01

We present a new method for generating two-dimensional maps of the cerebral cortex. Our computerized, two-stage flattening method takes as its input any well-defined representation of a surface within the three-dimensional cortex. The first stage rapidly converts this surface to a topologically correct two-dimensional map, without regard for the amount of distortion introduced. The second stage reduces distortions using a multiresolution strategy that makes gross shape changes on a coarsely sampled map and further shape refinements on progressively finer resolution maps. We demonstrate the utility of this approach by creating flat maps of the entire cerebral cortex in the macaque monkey and by displaying various types of experimental data on such maps. We also introduce a surface-based coordinate system that has advantages over conventional stereotaxic coordinates and is relevant to studies of cortical organization in humans as well as non-human primates. Together, these methods provide an improved basis for quantitative studies of individual variability in cortical organization.

Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex

PubMed Central

Laguesse, Sophie; Close, Pierre; Van Hees, Laura; Chariot, Alain; Malgrange, Brigitte; Nguyen, Laurent

2017-01-01

The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective α-tubulin acetylation. However, this complex is already expressed by cortical progenitors where it may regulate the early steps of migration by targeting additional proteins. Here we report that connexin-43 (Cx43), which is strongly expressed by cortical progenitors and whose depletion impairs projection neuron migration, requires Elongator expression for its proper acetylation. Indeed, we show that Cx43 acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43 acetylation requires Elongator in different cellular contexts. Moreover, we show that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report that acetylation of Cx43 regulates its membrane distribution in apical progenitors of the cerebral cortex. PMID:28507509

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Fractal dimension as an index of brain cortical changes throughout life.

PubMed

Kalmanti, Elina; Maris, Thomas G

2007-01-01

The fractal dimension (FD) of the cerebral cortex was measured in 93 individuals, aged from 3 months to 78 years, with normal brain MRI's in order to compare the convolutions of the cerebral cortex between genders and age groups. Image J, an image processing program, was used to skeletonize cerebral cortex and the box counting method applied. FDs on slices taken from left and right hemispheres were calculated. Our results showed a significant degree of lateralization in the left hemisphere. It appears that basal ganglia development, mainly in the left hemisphere, is heavily dependent upon age until puberty. In addition, both left and right cortex development equally depends on age until puberty, while the corresponding right hemisphere convolutions continue to develop until a later stage. An increased developmental activity appears between the ages of 1 and 15 years, indicating a significant brain remodelling during childhood and adolescence. In infancy, only changes in basal ganglia are observed, while the right hemisphere continues to remodel in adulthood.

Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats.

PubMed

Cauli, Omar; López-Larrubia, Pilar; Rodrigo, Regina; Agusti, Ana; Boix, Jordi; Nieto-Charques, Laura; Cerdán, Sebastián; Felipo, Vicente

2011-02-01

Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans blue-albumin extravasation. Increased IP arises from an early increase of blood-brain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Changes in Somatosensory Responsiveness in Behaving Primates

DTIC Science & Technology

1988-08-01

visually vs. vibratory-triggered movements; 2) to record from the cerebral cortex of awake , behaving monkeys during the performance of these sensory...vibratory-triggered movements; 2) to record from the cerebral cortex of awake , behaving monkeys during the performance of these sensory-triggered...recording chamber was implanted over the forelimb * region of the left sensorimotor cortices following a craniotomy and secured with smaller bolts and the

Biological substrates of schizophrenia.

PubMed

Kovelman, J A; Scheibel, A B

1986-01-01

Schizophrenia is increasingly believed to represent a group of organic disorders which primarily, although not exclusively, affect the central nervous system. Our purpose is to review a representative sample of twentieth-century literature which speaks to the biological substrates of the syndrome. Subjects reviewed include genetic and environmental contributions to the onset of illness, early and recent findings of gross structural anomalies, and apparent histopathological alterations in cerebral cortex, cerebellar vermis, limbic system, and brain stem, as well as problems of cerebral asymmetry. Data from a diverse group of electrophysiological studies reveal several promising correlates of these areas of investigation. Despite the inconsistent nature of the findings to date, several themes have begun to emerge, including patterns of hypofrontal/hyperparietal regional cerebral flow and glucose utilization, left hemispheric dysfunction, and deficits of interhemispheric information processing. The interpretation and significance of these emerging patterns remains unclear and must await more profound insights into the nature of normal and abnormal cerebral function.

Changes in Cerebral Cortex of Children Treated for Medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Arthur K.; Marcus, Karen J.; Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA

2007-07-15

Purpose: Children with medulloblastoma undergo surgery, radiotherapy, and chemotherapy. After treatment, these children have numerous structural abnormalities. Using high-resolution magnetic resonance imaging, we measured the thickness of the cerebral cortex in a group of medulloblastoma patients and a group of normally developing children. Methods and Materials: We obtained magnetic resonance imaging scans and measured the cortical thickness in 9 children after treatment of medulloblastoma. The measurements from these children were compared with the measurements from age- and gender-matched normally developing children previously scanned. For additional comparison, the pattern of thickness change was compared with the cortical thickness maps from amore » larger group of 65 normally developing children. Results: In the left hemisphere, relatively thinner cortex was found in the perirolandic region and the parieto-occipital lobe. In the right hemisphere, relatively thinner cortex was found in the parietal lobe, posterior superior temporal gyrus, and lateral temporal lobe. These regions of cortical thinning overlapped with the regions of cortex that undergo normal age-related thinning. Conclusion: The spatial distribution of cortical thinning suggested that the areas of cortex that are undergoing development are more sensitive to the effects of treatment of medulloblastoma. Such quantitative methods may improve our understanding of the biologic effects that treatment has on the cerebral development and their neuropsychological implications.« less

Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

2017-04-01

Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α 2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

PubMed

Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

2018-04-01

Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

Cyclooxygenase system contributes to the maintenance of post convulsive period of epileptic phenomena in the genetically epileptic El mice.

PubMed

Okada, Kazumasa; Yamashita, Uki; Tsuji, Sadatoshi

2006-09-01

Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up-regulated in the brain of human epilepsy patients and animal models of epilepsy. We investigated the effect of inflammatory responses induced by intramuscular injection of turpentine on the epileptic phenomenon in genetically epileptic El mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups to induce convulsion), duration of actual convulsion and duration of post actual convulsive period (period from the offset of convulsion to full recovery) were evaluated. The post actual convulsive period was prolonged without any change of seizure threshold or duration of actual convulsion 24 h after turpentine injection. Although pretreatment with indomethacin for one week did not change the seizure parameters, indomethacin suppressed the prolongation of the post actual convulsive period induced by turpentine. The mRNA expression of IL-1beta, IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no difference in the mRNA expression in the cerebral cortex before and 24 h after seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were up-regulated 24 h after turpentine injection. On the other hand, the up-regulated mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine treatment were not suppressed by indomethacin. These results suggest that prostaglandins induced with COX-2 in the cerebral cortex seem to play an important role in the maintenance of the post convulsive period, but not in induction and maintenance of the actual convulsive state.

[Effects of electromagnetic pulse on blood-brain barrier permeability and tight junction proteins in rats].

PubMed

Qiu, Lian-bo; Ding, Gui-rong; Zhang, Ya-mei; Zhou, Yan; Wang, Xiao-wu; Li, Kang-chu; Xu, Sheng-long; Tan, Juan; Zhou, Jia-xing; Guo, Guo-zhen

2009-09-01

To study the effect of electromagnetic pulse (EMP) on the permeability of blood-brain barrier, tight junction (TJ)-associated protein expression and localization in rats. 66 male SD rats, weighing (200 approximately 250) g, were sham or whole-body exposed to EMP at 200 kV/m for 200 pulses. The repetition rate was 1 Hz. The permeability of the blood-brain barrier in rats was assessed by albumin immunohistochemistry. The expression of typical tight junction protein ZO-1 and occludin in both cerebral cortex homogenate and cerebral cortex microvessel homogenate was analyzed by the Western blotting and the distribution of ZO-1 and occludin was examined by immunofluorescence microscopy. In the sham exposure rats, no brain capillaries showed albumin leakage, at 0.5 h after 200 kV/m EMP exposure for 200 pulses; a few brain capillaries with extravasated serum albumin was found, with the time extended, the number of brain capillaries with extravasated serum albumin increased, and reached the peak at 3 h, then began to recover at 6 h. In addition, no change in the distribution of the occludin was found after EMP exposure. Total occludin expression had no significant change compared with the control. However, the expression level of ZO-1 significantly decreased at 1 h and 3 h after EMP exposure in both cerebral cortex homogenate and cerebral cortex microvessel homogenate. Furthermore, immunofluorescence studies also showed alterations in ZO-1 protein localization in cerebral cortex microvessel. The EMP exposure (200 kV/m, 200 pulses) could increase blood-brain barrier permeability in rat, and this change is associated with specific alterations in tight junction protein ZO-1.

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

PubMed

Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Rebelo, Joyce; Damiani, Adriani P; Pereira, Maiara; Andrade, Vanessa M; Gava, Fernanda F; Valvassori, Samira S; Schuck, Patricia F; Ferreira, Gustavo C; Streck, Emilio L

2017-08-01

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

Connectivity-driven white matter scaling and folding in primate cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

2010-01-01

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290

Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status.

PubMed

Pélerin, Hélène; Jouin, Mélanie; Lallemand, Marie-Sylvie; Alessandri, Jean-Marc; Cunnane, Stephen C; Langelier, Bénédicte; Guesnet, Philippe

2014-11-01

Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

PubMed Central

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2 -/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

PubMed

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

PubMed Central

Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

2013-01-01

How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later. PMID:24155697

Updated energy budgets for neural computation in the neocortex and cerebellum

PubMed Central

Howarth, Clare; Gleeson, Padraig; Attwell, David

2012-01-01

The brain's energy supply determines its information processing power, and generates functional imaging signals. The energy use on the different subcellular processes underlying neural information processing has been estimated previously for the grey matter of the cerebral and cerebellar cortex. However, these estimates need reevaluating following recent work demonstrating that action potentials in mammalian neurons are much more energy efficient than was previously thought. Using this new knowledge, this paper provides revised estimates for the energy expenditure on neural computation in a simple model for the cerebral cortex and a detailed model of the cerebellar cortex. In cerebral cortex, most signaling energy (50%) is used on postsynaptic glutamate receptors, 21% is used on action potentials, 20% on resting potentials, 5% on presynaptic transmitter release, and 4% on transmitter recycling. In the cerebellar cortex, excitatory neurons use 75% and inhibitory neurons 25% of the signaling energy, and most energy is used on information processing by non-principal neurons: Purkinje cells use only 15% of the signaling energy. The majority of cerebellar signaling energy use is on the maintenance of resting potentials (54%) and postsynaptic receptors (22%), while action potentials account for only 17% of the signaling energy use. PMID:22434069

Effects of oxotremorine on local glucose utilization in the rat cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dam, M.; Wamsley, J.K.; Rapoport, S.I.

The (/sup 14/C)2-deoxy-D-glucose technique was used to examine the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in the cerebral cortex of the unanesthetized rat. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex. In the neocortex, OXO was more potent in elevating LCGU of the auditory, frontal, and sensorimotor regions compared with the visual cortex. Within these neocortical regions, OXO effects were greatest in cortical layers IV and V. OXO effects were more dramatic in the neocortex than in the meso- or paleocortex, andmore » no significant effect occurred in the perirhinal and pyriform cortices. OXO-induced LCGU increases were not influenced by methylatropine (1 mg/kg, s.c.) but were antagonized completely by scopolamine (2.5 mg/kg, i.p.). Scopolamine reduced LCGU in layer IV of the auditory cortex and in the retrosplenial cortex. The distribution and magnitude of the cortical LCGU response to OXO apparently were related to the distributions of cholinergic neurochemical markers, especially high affinity muscarinic binding sites.« less

The basic nonuniformity of the cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.; Lent, Roberto

2008-01-01

Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221–244], who found a steady number of approximately 110 neurons underneath a surface area of 750 μm2 (147,000 underneath 1 mm2) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm2 of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons. PMID:18689685

The basic nonuniformity of the cerebral cortex.

PubMed

Herculano-Houzel, Suzana; Collins, Christine E; Wong, Peiyan; Kaas, Jon H; Lent, Roberto

2008-08-26

Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221-244], who found a steady number of approximately 110 neurons underneath a surface area of 750 microm(2) (147,000 underneath 1 mm(2)) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm(2) of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons.

Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates

NASA Astrophysics Data System (ADS)

Peuser, Jörn; Belhaj-Saif, Abderraouf; Hamadjida, Adjia; Schmidlin, Eric; Gindrat, Anne-Dominique; Völker, Andreas Charles; Zakharov, Pavel; Hoogewoud, Henri-Marcel; Rouiller, Eric M.; Scheffold, Frank

2011-09-01

The nonhuman primate model is suitable to study mechanisms of functional recovery following lesion of the cerebral cortex (motor cortex), on which therapeutic strategies can be tested. To interpret behavioral data (time course and extent of functional recovery), it is crucial to monitor the properties of the experimental cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5 weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood flow) and anatomical assessment with magnetic resonance imaging (T2-weighted MRI). The cerebral blood flow, measured online during subsequent injections of the ibotenic acid in the motor cortex, exhibited a dramatic increase, still present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the cerebral blood flow was strongly reduced (below reference level) and the hypersignal disappeared from the MRI scan, although the lesion was permanent as histologically assessed post-mortem. The MRI data were similar in the second monkey. Our experiments suggest that LSI and MRI, although they reflect different features, vary in parallel during a few weeks following an excitotoxic cortical lesion.

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2017-04-01

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.

Cerebral Lateralization and Aggression.

ERIC Educational Resources Information Center

Hillbrand, Marc; And Others

1994-01-01

A resurgence of interest in the relationship between cerebral lateralization (the functional asymmetry of the cerebral cortex) and aggression has occurred. Most recent studies have found that individuals with abnormal patterns of lateralization are overrepresented among violent individuals. Intervening variables (such as drug and alcohol abuse)…

NADPH-diaphorase activity and neurovascular coupling in the rat cerebral cortex.

PubMed

Vlasenko, O V; Maisky, V A; Maznychenko, A V; Pilyavskii, A I

2008-01-01

The distribution of NADPH-diaphorase-reactive (NADPH-dr) neurons and neuronal processes in the cerebral cortex and basal forebrain and their association with parenchymal vessels were studied in normal adult rats using NADPH-d histochemical protocol. The intensely stained cortical interneurons and reactive subcortically originating afferents, and stained microvessels were examined through a light microscope at law (x250) and high (x630) magnifications. NADPH-dr interneurons were concentrated in layers 2-6 of the M1 and M2 areas. However, clear predominance in their concentration (14 +/- 0.8 P < 0.05 per section) was found in layer 6. A mean number of labeled neurons in auditory (AuV), granular and agranular (GI, AIP) areas of the insular cortex was calculated to reach 12.3 +/- 0.7, 18.5 +/- 1.0 and 23.3 +/- 1.7 units per section, respectively (P < 0.05). The distinct apposition of labelled neurons to intracortical vessels was found in the M1, M2. The order of frequency of neurovascular coupling in different zones of the cerebral cortex was as following sequence: AuV (31.2%, n = 1040) > GI (18.0%, n = 640) > S1 (13.3%, n = 720) > M1 (6.3%, n = 1360). A large number of structural associations between labeled cells and vessels in the temporal and insular cortex indicate that NADPH-d-reactive interneurons can contribute to regulation of the cerebral regional blood flow in these areas.

Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats.

PubMed

Akinyemi, Ayodele Jacob; Oboh, Ganiyu; Fadaka, Adewale Oluwaseun; Olatunji, Babawale Peter; Akomolafe, Seun

2017-09-01

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase potential with limited information on how they regulate acetylcholinesterase (AChE) gene expression. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA gene expression level in cadmium (Cd)-treated rats. Furthermore, in vitro effect of different concentrations of curcumin (1-5μg/mL) on rat cerebral cortex AChE activity was assessed. Animals were divided into six groups (n=6): group 1 serve as control (without Cd) and receive saline/vehicle, group 2 receive saline plus curcumin at 25mg/kg, group 3 receive saline plus curcumin 50mg/kg, group 4 receive Cd plus vehicle, group 5 receive Cd plus curcumin at 25mg/kg and group 6 receive Cd plus curcumin at 50mg/kg. Rats received Cd (2.5mg/kg) and curcumin (25 and 50mg/kg, respectively) by oral gavage for 7days. Acetylcholinesterase activity was measured by Ellman's method and AChE expression was carried out by a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay. We observed that acute administration of Cd increased acetylcholinesterase activity and in addition caused a significant (P<0.05) increase in AChE mRNA levels in whole cerebral cortex when compared to control group. However, co-treatment with curcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd-treated group. In addition, curcumin inhibits rat cerebral cortex AChE activity in vitro. In conclusion, curcumin exhibit anti-acetylcholinesterase activity and suppressed AChE mRNA gene expression level in Cd exposed rats, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric-derived compound in treating neurological disorders including Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism.

PubMed

Weiss, Harvey R; Liu, Xia; Zhang, Qihang; Chi, Oak Z

2007-08-15

Because there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that these animals would have an altered regional cerebral O2 consumption that might be associated with autism. We also examined whether the altered cerebral O2 consumption was related to changes in the importance of N-methyl-D-aspartate (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg, competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O2 consumption in the cortex (6.2 +/- 0.6 ml O2/min/100 g Eker vs. 4.7 +/- 0.4 Long Evans), hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated in Eker rats at baseline, but cerebral O2 extraction was similar. CGS-19755 significantly lowered O2 consumption in the cortex (2.8 +/- 0.3), hippocampus, and pons of the Long Evans rats but had no effect on cortex (5.8 +/- 0.8) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. NMDA receptor protein levels (NR1 subunit) were similar between groups. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not related to NMDA receptor activation. In fact, the importance of NMDA receptors in the control of basal cerebral O2 consumption was reduced. This might have important implications in the treatment of autism. Copyright 2007 Wiley-Liss, Inc.

Intracellular Progesterone Receptor Mediates the Increase in Glioblastoma Growth Induced by Progesterone in the Rat Brain.

PubMed

Germán-Castelán, Liliana; Manjarrez-Marmolejo, Joaquín; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio

2016-08-01

Progesterone (P) is a steroid hormone involved in the development of several types of cancer including astrocytomas, the most common and malignant brain tumors. We undertook this study to investigate the effects of P on the growth and infiltration of a tumor caused by the xenotransplant of U87 cells derived from a human astrocytoma grade IV (glioblastoma) in the cerebral cortex of male rats and the participation of intracellular progesterone receptor (PR) on these effects. Eight weeks after the implantation of U87 cells in the cerebral cortex, we administered phosphorothioated antisense oligodeoxynucleotides (ODNs) to silence the expression of PR. This treatment lasted 15 days and was administered at the site of glioblastoma cells implantation using Alzet osmotic pumps. Vehicle (propylene glycol) or P 4 (400 μg/100 g) was subcutaneously injected for 14 days starting 1 day after the beginning of ODN administration. We observed that P significantly increased glioblastoma tumor area and infiltration length as compared with vehicle, whereas PR antisense ODNs blocked these effects. P, through the interaction with PR, increases the area and infiltration of a brain tumor formed from the xenotransplant of human glioblastoma-derived U87 cells in the cerebral cortex of the rat. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats.

PubMed

da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

2015-01-01

Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

PubMed Central

da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

2015-01-01

Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings. PMID:26649198

The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices

PubMed Central

2012-01-01

Background A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Methods Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10–20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Results Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Conclusions Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections. PMID:23199306

Delayed Influence of Spinal Cord Injury on the Amino Acids of NO• Metabolism in Rat Cerebral Cortex Is Attenuated by Thiamine

PubMed Central

Boyko, Alexandra; Ksenofontov, Alexander; Ryabov, Sergey; Baratova, Lyudmila; Graf, Anastasia; Bunik, Victoria

2018-01-01

Severe spinal cord injuries (SCIs) result in chronic neuroinflammation in the brain, associated with the development of cognitive and behavioral impairments. Nitric oxide (NO•) is a gaseous messenger involved in neuronal signaling and inflammation, contributing to nitrosative stress under dysregulated production of reactive nitrogen species. In this work, biochemical changes induced in the cerebral cortex of rats 8 weeks after SCI are assessed by quantification of the levels of amino acids participating in the NO• and glutathione metabolism. The contribution of the injury-induced neurodegeneration is revealed by comparison of the SCI- and laminectomy (LE)-subjected animals. Effects of the operative interventions are assessed by comparison of the operated (LE/SCI) and non-operated animals. Lower ratios of citrulline (Cit) to arginine (Arg) or Cit to ornithine and a more profound decrease in the ratio of lysine to glycine distinguish SCI animals from those after LE. The data suggest decreased NO• production from both Arg and homoarginine in the cortex 8 weeks after SCI. Both LE and SCI groups show a strong decrease in the level of cortex glutathione. The neurotropic, anti-inflammatory, and antioxidant actions of thiamine (vitamin B1) prompted us to study the thiamine effects on the SCI-induced changes in the NO• and glutathione metabolism. A thiamine injection (400 mg/kg intraperitoneally) within 24 h after SCI abrogates the changes in the cerebral cortex amino acids related to NO•. Thiamine-induced normalization of the brain glutathione levels after LE and SCI may involve increased supply of glutamate for glutathione biosynthesis. Thus, thiamine protects from sequelae of SCI on NO•-related amino acids and glutathione in cerebral cortex. PMID:29379782

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?

PubMed

Eyre, Janet A; Smith, Martin; Dabydeen, Lyvia; Clowry, Gavin J; Petacchi, Eliza; Battini, Roberta; Guzzetta, Andrea; Cioni, Giovanni

2007-11-01

Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity-dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment. Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects. Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development. Rather than representing "reparative plasticity," increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life.

Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

PubMed Central

Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

2014-01-01

Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

PubMed

Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

2017-02-01

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

Anatomy of the Temporal Lobe

PubMed Central

Kiernan, J. A.

2012-01-01

Only primates have temporal lobes, which are largest in man, accommodating 17% of the cerebral cortex and including areas with auditory, olfactory, vestibular, visual and linguistic functions. The hippocampal formation, on the medial side of the lobe, includes the parahippocampal gyrus, subiculum, hippocampus, dentate gyrus, and associated white matter, notably the fimbria, whose fibres continue into the fornix. The hippocampus is an inrolled gyrus that bulges into the temporal horn of the lateral ventricle. Association fibres connect all parts of the cerebral cortex with the parahippocampal gyrus and subiculum, which in turn project to the dentate gyrus. The largest efferent projection of the subiculum and hippocampus is through the fornix to the hypothalamus. The choroid fissure, alongside the fimbria, separates the temporal lobe from the optic tract, hypothalamus and midbrain. The amygdala comprises several nuclei on the medial aspect of the temporal lobe, mostly anterior the hippocampus and indenting the tip of the temporal horn. The amygdala receives input from the olfactory bulb and from association cortex for other modalities of sensation. Its major projections are to the septal area and prefrontal cortex, mediating emotional responses to sensory stimuli. The temporal lobe contains much subcortical white matter, with such named bundles as the anterior commissure, arcuate fasciculus, inferior longitudinal fasciculus and uncinate fasciculus, and Meyer's loop of the geniculocalcarine tract. This article also reviews arterial supply, venous drainage, and anatomical relations of the temporal lobe to adjacent intracranial and tympanic structures. PMID:22934160

Identification of proteins in hyperglycemia and stroke animal models.

PubMed

Sung, Jin-Hee; Shah, Fawad-Ali; Gim, Sang-Ah; Koh, Phil-Ok

2016-01-01

Stroke is a major cause of disability and death in adults. Diabetes mellitus is a metabolic disorder that strongly increases the risk of severe vascular diseases. This study compared changes in proteins of the cerebral cortex during ischemic brain injury between nondiabetic and diabetic animals. Adult male rats were injected with streptozotocin (40 mg/kg) via the intraperitoneal route to induce diabetes and underwent surgical middle cerebral artery occlusion (MCAO) 4 wk after streptozotocin treatment. Cerebral cortex tissues were collected 24 h after MCAO and cerebral cortex proteins were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Several proteins were identified as differentially expressed between nondiabetic and diabetic animals. Among the identified proteins, we focused on the following metabolism-related enzymes: isocitrate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, adenosylhomocysteinase, pyruvate kinase, and glucose-6-phosphate isomerase (neuroleukin). Expression of these proteins was decreased in animals that underwent MCAO. Moreover, protein expression was reduced to a greater extent in diabetic animals than in nondiabetic animals. Reverse transcription-polymerase chain reaction analysis confirmed that the diabetic condition exacerbates the decrease in expression of metabolism-related proteins after MCAO. These results suggest that the diabetic condition may exacerbate brain damage during focal cerebral ischemia through the downregulation of metabolism-related proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.

PubMed

Zhu, Yu-Peng; Xi, Shu-Hua; Li, Ming-Yan; Ding, Ting-Ting; Liu, Nan; Cao, Fu-Yuan; Zeng, Yang; Liu, Xiao-Jing; Tong, Jun-Wang; Jiang, Shou-Fang

2017-03-01

Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V).

PubMed

Hayashi, Kentaro; Mochizuki, Yoko; Takeuchi, Ryoko; Shimizu, Toshio; Nagao, Masahiro; Watabe, Kazuhiko; Arai, Nobutaka; Oyanagi, Kiyomitsu; Onodera, Osamu; Hayashi, Masaharu; Takahashi, Hitoshi; Kakita, Akiyoshi; Isozaki, Eiji

2016-09-30

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.

Cognition in Domestic Dogs: Object Permanence & Social Cueing

ERIC Educational Resources Information Center

Clotfelter, Ethan D.; Hollis, Karen L.

2008-01-01

Cognition is a general term describing the mental capacities of an animal, and often includes the ability to categorize, remember, and communicate about objects in the environment. Numerous regions of the telencephalon (cerebral cortex and limbic system) are responsible for these cognitive functions. Although many researchers have used traditional…

Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex.

PubMed

Castaldo, Pasqualina; Magi, Simona; Gaetani, Silvana; Cassano, Tommaso; Ferraro, Luca; Antonelli, Tiziana; Amoroso, Salvatore; Cuomo, Vincenzo

2007-09-01

Prenatal exposure to the CB1 receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta9-tetrahydrocannabinol (Delta9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born from vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of Vmaxl-[3H]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 receptor agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy.

Measurement of cerebral blood flow rate and its relationship with brain function using optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Jian; Wang, Yi; Zhao, Yuqian; Dou, Shidan; Ma, Yushu; Ma, Zhenhe

2016-03-01

Activity of brain neurons will lead to changes in local blood flow rate (BFR). Thus, it is important to measure the local BFR of cerebral cortex on research of neuron activity in vivo, such as rehabilitation evaluation after stroke, etc. Currently, laser Doppler flowmetry is commonly used for blood flow measurement, however, relatively low resolution limits its application. Optical coherence tomography (OCT) is a powerful noninvasive 3D imaging modality with high temporal and spatial resolutions. Furthermore, OCT can provide flow distribution image by calculating Doppler frequency shift which makes it possible for blood flow rate measurement. In this paper, we applied OCT to measure the blood flow rate of the primary motor cortex in rats. The animal was immobilized and anesthetized with isoflurane, an incision was made along the sagittal suture, and bone was exposed. A skull window was opened on the primary motor cortex. Then, blood flow rate changes in the primary motor cortex were monitored by our homemade spectral domain OCT with a stimulation of the passive movement of the front legs. Finally, we established the relationship between blood flow rate and the test design. The aim is to demonstrate the potential of OCT in the evaluation of cerebral cortex function.

Characteristics of (3H)2-Deoxyglucose Uptake by Slices of Rat Cerebral Cortex

DTIC Science & Technology

1983-05-17

phlorizin or by phloretin , two compounds known to inhibit glucose transport by kidney and by erythrocytes, respectively. Net [-̂ H]2-de- oxyglucose uptake...Hexoses 53 17. The Effect of Phlorizin and Phloretin on Net [3H]2-Deoxy- glucose Transport by Slices of Cerebral Cortex 55 18. The Effect of Sodium...LeFevre, 1961). Transport by erythrocytes is not dependent on sodium (Silverman, 1976). Transport is, however, sensitive to inhibition by phloretin

Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex.

PubMed

Wachi, Tomoka; Cornell, Brett; Marshall, Courtney; Zhukarev, Vladimir; Baas, Peter W; Toyo-oka, Kazuhito

2016-06-01

14-3-3 proteins are ubiquitously-expressed and multifunctional proteins. There are seven isoforms in mammals with a high level of homology, suggesting potential functional redundancy. We previously found that two of seven isoforms, 14-3-3epsilon and 14-3-3zeta, are important for brain development, in particular, radial migration of pyramidal neurons in the developing cerebral cortex. In this work, we analyzed the function of another isoform, the protein 14-3-3gamma, with respect to neuronal migration in the developing cortex. We found that in utero 14-3-3gamma-deficiency resulted in delays in neuronal migration as well as morphological defects. Migrating neurons deficient in 14-3-3gamma displayed a thicker leading process stem, and the basal ends of neurons were not able to reach the boundary between the cortical plate and the marginal zone. Consistent with the results obtained from in utero electroporation, time-lapse live imaging of brain slices revealed that the ablation of the 14-3-3gamma proteins in pyramidal neurons slowed down their migration. In addition, the 14-3-3gamma deficient neurons showed morphological abnormalities, including increased multipolar neurons with a thicker leading processes stem during migration. These results indicate that the 14-3-3gamma proteins play an important role in radial migration by regulating the morphology of migrating neurons in the cerebral cortex. The findings underscore the pathological phenotypes of brain development associated with the disruption of different 14-3-3 proteins and will advance the preclinical data regarding disorders caused by neuronal migration defects. © 2015 Wiley Periodicals, Inc.

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

PubMed

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

2017-07-01

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

Phenol emulsion-enhanced DNA-driven subtractive cDNA cloning: isolation of low-abundance monkey cortex-specific mRNAs.

PubMed Central

Travis, G H; Sutcliffe, J G

1988-01-01

To isolate cDNA clones of low-abundance mRNAs expressed in monkey cerebral cortex but absent from cerebellum, we developed an improved subtractive cDNA cloning procedure that requires only modest quantities of mRNA. Plasmid DNA from a monkey cerebellum cDNA library was hybridized in large excess to radiolabeled monkey cortex cDNA in a phenol emulsion-enhanced reaction. The unhybridized cortex cDNA was isolated by chromatography on hydroxyapatite and used to probe colonies from a monkey cortex cDNA library. Of 60,000 colonies screened, 163 clones were isolated and confirmed by colony hybridization or RNA blotting to represent mRNAs, ranging from 0.001% to 0.1% abundance, specific to or highly enriched in cerebral cortex relative to cerebellum. Clones of one medium-abundance mRNA were recovered almost quantitatively. Two of the lower-abundance mRNAs were expressed at levels reduced by a factor of 10 in Alzheimer disease relative to normal human cortex. One of these was identified as the monkey preprosomatostatin I mRNA. Images PMID:2894033

Comparing brain activity patterns during spontaneous exploratory and cue-instructed learning using single photon-emission computed tomography (SPECT) imaging of regional cerebral blood flow in freely behaving rats.

PubMed

Mannewitz, A; Bock, J; Kreitz, S; Hess, A; Goldschmidt, J; Scheich, H; Braun, Katharina

2018-05-01

Learning can be categorized into cue-instructed and spontaneous learning types; however, so far, there is no detailed comparative analysis of specific brain pathways involved in these learning types. The aim of this study was to compare brain activity patterns during these learning tasks using the in vivo imaging technique of single photon-emission computed tomography (SPECT) of regional cerebral blood flow (rCBF). During spontaneous exploratory learning, higher levels of rCBF compared to cue-instructed learning were observed in motor control regions, including specific subregions of the motor cortex and the striatum, as well as in regions of sensory pathways including olfactory, somatosensory, and visual modalities. In addition, elevated activity was found in limbic areas, including specific subregions of the hippocampal formation, the amygdala, and the insula. The main difference between the two learning paradigms analyzed in this study was the higher rCBF observed in prefrontal cortical regions during cue-instructed learning when compared to spontaneous learning. Higher rCBF during cue-instructed learning was also observed in the anterior insular cortex and in limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes showed hemispheric lateralization. Taken together, our study is the first to compare partly lateralized brain activity patterns during two different types of learning.

Functional brain imaging of a complex navigation task following one night of total sleep deprivation

NASA Technical Reports Server (NTRS)

Strangman, Gary; Thompson, John H.; Strauss, Monica M.; Marshburn, Thomas H.; Sutton, Jeffrey P.

2006-01-01

Study Objectives: To assess the cerebral effects associated with sleep deprivation in a simulation of a complex, real-world, high-risk task. Design and Interventions: A two-week, repeated measures, cross-over experimental protocol, with counterbalanced orders of normal sleep (NS) and total sleep deprivation (TSD). Setting: Each subject underwent functional magnetic resonance imaging (fMRI) while performing a dual-joystick, 3D sensorimotor navigation task (simulated orbital docking). Scanning was performed twice per subject, once following a night of normal sleep (NS), and once following a single night of total sleep deprivation (TSD). Five runs (eight 24s docking trials each) were performed during each scanning session. Participants: Six healthy, young, right-handed volunteers (2 women; mean age 20) participated. Measurements and Results: Behavioral performance on multiple measures was comparable in the two sleep conditions. Neuroimaging results within sleep conditions revealed similar locations of peak activity for NS and TSD, including left sensorimotor cortex, left precuneus (BA 7), and right visual areas (BA 18/19). However, cerebral activation following TSD was substantially larger and exhibited higher amplitude modulations from baseline. When directly comparing NS and TSD, most regions exhibited TSD>NS activity, including multiple prefrontal cortical areas (BA 8/9,44/45,47), lateral parieto-occipital areas (BA 19/39, 40), superior temporal cortex (BA 22), and bilateral thalamus and amygdala. Only left parietal cortex (BA 7) demonstrated NS>TSD activity. Conclusions: The large network of cerebral differences between the two conditions, even with comparable behavioral performance, suggests the possibility of detecting TSD-induced stress via functional brain imaging techniques on complex tasks before stress-induced failures.

The regional cerebral blood flow changes in major depressive disorder with and without psychotic features.

PubMed

Gonul, Ali Saffet; Kula, Mustafa; Bilgin, Arzu Guler; Tutus, Ahmet; Oguz, Aslan

2004-09-01

Depressive patients with psychotic features demonstrate distinct biological abnormalities in the hypothalamic-pituitary-adrenal axis (HPA), dopaminergic activity, electroencephalogram sleep profiles and measures of serotonergic function when compared to nonpsychotic depressive patients. However, very few functional neuroimaging studies were specifically designed for studying the effects of psychotic features on neuroimaging findings in depressed patients. The objective of the present study was to compare brain Single Photon Emission Tomography (SPECT) images in a group of unmedicated depressive patients with and without psychotic features. Twenty-eight patients who fully met DSM-IV criteria for major depressive disorder (MDD, 12 had psychotic features) were included in the study. They were compared with 16 control subjects matched for age, gender and education. Both psychotic and nonpsychotic depressed patients showed significantly lower regional cerebral blood flow (rCBF) values in the left and right superior frontal cortex, and left anterior cingulate cortex compared to those of controls. In comparison with depressive patients without psychotic features (DwoPF), depressive patients with psychotic features (DwPF) showed significantly lower rCBF perfusion ratios in left parietal cortex, left cerebellum but had higher rCBF perfusion ratio in the left inferior frontal cortex and caudate nucleus. The present study showed that DwPF have a different rCBF pattern compared to patients without psychotic features. Abnormalities involving inferior frontal cortex, striatum and cerebellum may play an important role in the generation of psychotic symptoms in depression.

Hemodynamic changes in a rat parietal cortex after endothelin-1-induced middle cerebral artery occlusion monitored by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Jian; Ma, Yushu; Dou, Shidan; Wang, Yi; La, Dongsheng; Liu, Jianghong; Ma, Zhenhe

2016-07-01

A blockage of the middle cerebral artery (MCA) on the cortical branch will seriously affect the blood supply of the cerebral cortex. Real-time monitoring of MCA hemodynamic parameters is critical for therapy and rehabilitation. Optical coherence tomography (OCT) is a powerful imaging modality that can produce not only structural images but also functional information on the tissue. We use OCT to detect hemodynamic changes after MCA branch occlusion. We injected a selected dose of endothelin-1 (ET-1) at a depth of 1 mm near the MCA and let the blood vessels follow a process first of occlusion and then of slow reperfusion as realistically as possible to simulate local cerebral ischemia. During this period, we used optical microangiography and Doppler OCT to obtain multiple hemodynamic MCA parameters. The change trend of these parameters from before to after ET-1 injection clearly reflects the dynamic regularity of the MCA. These results show the mechanism of the cerebral ischemia-reperfusion process after a transient middle cerebral artery occlusion and confirm that OCT can be used to monitor hemodynamic parameters.

The effects of whole body vibration combined computerized postural control training on the lower extremity muscle activity and cerebral cortex activity in stroke patients.

PubMed

Uhm, Yo-Han; Yang, Dae-Jung

2018-02-01

[Purpose] The purpose of this study was to examine the effect of computerized postural control training using whole body vibration on lower limb muscle activity and cerebral cortical activation in acute stroke patients. [Subjects and Methods] Thirty stroke patients participated and were divided into groups of 10, a group of the computerized postural control training using whole body vibration (Group I), the computerized postural control training combined with aero step (Group II) and computerized postural control training (Group III). MP100 was used to measure lower limb muscle activity, and QEEG-8 was used to measure cerebral cortical activation. [Results] Comparison of muscle activity and cerebral cortical activation before and after intervention between groups showed that Group I had significant differences in lower limb muscle activity and cerebral cortical activation compared to Groups II and III. [Conclusion] This study showed that whole body vibration combined computerized postural control training is effective for improving muscle activity and cerebral cortex activity in stroke patients.

The Effect of Diazoxide Upon Heat Shock Protein and Physiological Response to Hemorrhagic Shock and Cerebral Stroke

DTIC Science & Technology

2006-06-16

ischemic kidney model [121]. Photothrombic brain injury elicits the expression of HSP70 and HSP27 . HSP70 expression as early as one hour post-trauma...delineated the area of necrosis at 24 hours post-thrombic injury in ipsilateral cortex. HSP27 expression also was found to be upregulated and in fact...more globally expressed in the entire ipsilateral cerebral cortex, primarily in astrocytes [122]. 25 HSP25 and HSP27 Research demonstrates

A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex.

PubMed

Sheardown, M J

1988-04-13

L(+)-AP4 (2-amino-4-phosphonobutyrate) depolarized slices of rat cerebral cortex, when applied following a 2 min priming application of quisqualate. This response diminishes with time and is not seen after NMDA application. A new selective non-N-methyl-D-aspartate (NMDA) antagonist, 6-cyano-7-nitro-2,3-dihydroxyquinoxaline (FG 9065), inhibits the L(+)-AP4 depolarization. It is argued that the response is mediated indirectly by postsynaptic quisqualate receptors.

FDG-PET study of the bilateral subthalamic nucleus stimulation effects on the regional cerebral metabolism in advanced Parkinson disease.

PubMed

Li, D; Zuo, C; Guan, Y; Zhao, Y; Shen, J; Zan, S; Sun, B

2006-01-01

The aim of the study was to evaluate the changes in regional cerebral metabolic rate of glucose (rCMRGlu) induced by bilateral subthalamic nucleurs (STN) stimulation in advanced Parkinson's disease (PD). 18F-Fluorodeoxyglucose (FDG) PET data obtained before and one month after stimulation were analyzed with statistical parametric mapping (SPM). As a result of clinically effective bilateral STN stimulation, rCMRGlu increased in lateral globus pallidus (GP), upper brain stem, dorsolateral prefrontal cortex (DLPFC) and posterior parietal-occipital cortex, and decreased in the orbital frontal cortex and parahippocampus gyrus (p < 0.001). We conclude that the alleviation of clinical symptoms in advanced PD by bilateral STN stimulation may be the result of activation of both ascending and descending pathways from STN and of restoration of the impaired higher-order cortex functions.

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.

PubMed

Morgan, V; Pickens, D; Gautam, S; Kessler, R; Mertz, H

2005-05-01

Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

On the Origin of Cortical Dopamine: Is it a Co-Transmitter in Noradrenergic Neurons?

PubMed Central

Devoto, Paola; Flore, Giovanna

2006-01-01

Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA. To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter. Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas. Systemic administration or intra-cortical perfusion of α2-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex. Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC. Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced. Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of α2-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex. Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration. Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex. The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions. PMID:18615131

On the origin of cortical dopamine: is it a co-transmitter in noradrenergic neurons?

PubMed

Devoto, Paola; Flore, Giovanna

2006-04-01

Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA.To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter.Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas.Systemic administration or intra-cortical perfusion of alpha(2)-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex.Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC.Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced.Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of alpha(2)-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex.Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration.Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex.The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions.

Constancy and trade-offs in the neuroanatomical and metabolic design of the cerebral cortex

PubMed Central

Karbowski, Jan

2014-01-01

Mammalian brains span about four orders of magnitude in cortical volume and have to operate in different environments that require diverse behavioral skills. Despite these geometric and behavioral diversities, the examination of cerebral cortex across species reveals that it contains a substantial number of conserved characteristics that are associated with neuroanatomy and metabolism, i.e., with neuronal connectivity and function. Some of these cortical constants or invariants have been known for a long time but not sufficiently appreciated, and others were only recently discovered. The focus of this review is to present the cortical invariants and discuss their role in the efficient information processing. Global conservation in neuroanatomy and metabolism, as well as their correlated regional and developmental variability suggest that these two parallel systems are mutually coupled. It is argued that energetic constraint on cortical organization can be strong if cerebral blood supplied is either below or above a certain level, and it is rather soft otherwise. Moreover, because maximization or minimization of parameters associated with cortical connectivity, function and cost often leads to conflicts in design, it is argued that the architecture of the cerebral cortex is a result of structural and functional compromises. PMID:24574975

Cerebral interactions of pain and reward and their relevance for chronic pain.

PubMed

Becker, Susanne; Gandhi, Wiebke; Schweinhardt, Petra

2012-06-29

Pain and reward are opponent, interacting processes. Such interactions are enabled by neuroanatomical and neurochemical overlaps of brain systems that process pain and reward. Cerebral processing of hedonic ('liking') and motivational ('wanting') aspects of reward can be separated: the orbitofrontal cortex and opioids play an important role for the hedonic experience, and the ventral striatum and dopamine predominantly process motivation for reward. Supported by neuroimaging studies, we present here the hypothesis that the orbitofrontal cortex and opioids are responsible for pain modulation by hedonic experience, while the ventral striatum and dopamine mediate motivational effects on pain. A rewarding stimulus that appears to be particularly important in the context of pain is pain relief. Further, reward, including pain relief, leads to operant learning, which can affect pain sensitivity. Indirect evidence points at brain mechanisms that might underlie pain relief as a reward and related operant learning but studies are scarce. Investigating the cerebral systems underlying pain-reward interactions as well as related operant learning holds the potential of better understanding mechanisms that contribute to the development and maintenance of chronic pain, as detailed in the last section of this review. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

PubMed

Ouchi, Y; Kakiuchi, T; Okada, H; Nishiyama, S; Tsukada, H

1999-03-15

To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain.

PubMed

Hawkes, Cheryl A; Gatherer, Maureen; Sharp, Matthew M; Dorr, Adrienne; Yuen, Ho Ming; Kalaria, Rajesh; Weller, Roy O; Carare, Roxana O

2013-04-01

Development of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is associated with failure of elimination of amyloid-β (Aβ) from the brain along perivascular basement membranes that form the pathways for drainage of interstitial fluid and solutes from the brain. In transgenic APP mouse models of AD, the severity of cerebral amyloid angiopathy is greater in the cerebral cortex and hippocampus, intermediate in the thalamus, and least in the striatum. In this study we test the hypothesis that age-related regional variation in (1) vascular basement membranes and (2) perivascular drainage of Aβ contribute to the different regional patterns of CAA in the mouse brain. Quantitative electron microscopy of the brains of 2-, 7-, and 23-month-old mice revealed significant age-related thickening of capillary basement membranes in cerebral cortex, hippocampus, and thalamus, but not in the striatum. Results from Western blotting and immunocytochemistry experiments showed a significant reduction in collagen IV in the cortex and hippocampus with age and a reduction in laminin and nidogen 2 in the cortex and striatum. Injection of soluble Aβ into the hippocampus or thalamus showed an age-related reduction in perivascular drainage from the hippocampus but not from the thalamus. The results of the study suggest that changes in vascular basement membranes and perivascular drainage with age differ between brain regions, in the mouse, in a manner that may help to explain the differential deposition of Aβ in the brain in AD and may facilitate development of improved therapeutic strategies to remove Aβ from the brain in AD. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Early optical detection of cerebral edema in vivo.

PubMed

Gill, Amandip S; Rajneesh, Kiran F; Owen, Christopher M; Yeh, James; Hsu, Mike; Binder, Devin K

2011-02-01

Cerebral edema is a significant cause of morbidity and mortality in diverse disease states. Currently, the means to detect progressive cerebral edema in vivo includes the use of intracranial pressure (ICP) monitors and/or serial radiological studies. However, ICP measurements exhibit a high degree of variability, and ICP monitors detect edema only after it becomes sufficient to significantly raise ICP. The authors report the development of 2 distinct minimally invasive fiberoptic near-infrared (NIR) techniques able to directly detect early cerebral edema. Cytotoxic brain edema was induced in adult CD1 mice via water intoxication by intraperitoneal water administration (30% body weight intraperitoneally). An implantable dual-fiberoptic probe was stereotactically placed into the cerebral cortex and connected to optical source and detector hardware. Optical sources consisted of either broadband halogen illumination or a single-wavelength NIR laser diode, and the detector was a sensitive NIR spectrometer or optical power meter. In one subset of animals, a left-sided craniectomy was performed to obtain cortical biopsies for water-content determination to verify cerebral edema. In another subset of animals, an ICP transducer was placed on the contralateral cortex, which was synchronized to a computer and time stamped. Using either broadband illumination with NIR spectroscopy or single-wavelength laser diode illumination with optical power meter detection, the authors detected a reduction in NIR optical reflectance during early cerebral edema. The time intervals between water injection (Time Point 0), optical trigger (defined as a 2-SD change in optical reflectance from baseline), and defined threshold ICP values of 10, 15 and 20 mm Hg were calculated. Reduction in NIR reflectance occurred significantly earlier than any of the ICP thresholds (p < 0.001). Saline-injected control mice exhibited a steady baseline optical signal. There was a significant correlation between reflectance change and tissue specific gravity of the cortical biopsies, further validating the dual-fiberoptic probe as a direct measure of cerebral edema. Compared with traditional ICP monitoring, the aforementioned minimally invasive NIR techniques allow for the significantly earlier detection of cerebral edema, which may be of clinical utility in the identification and thus early treatment of cerebral edema.

Neural Modeling and Imaging of the Cortical Interactions Underlying Syllable Production

ERIC Educational Resources Information Center

Guenther, Frank H.; Ghosh, Satrajit S.; Tourville, Jason A.

2006-01-01

This paper describes a neural model of speech acquisition and production that accounts for a wide range of acoustic, kinematic, and neuroimaging data concerning the control of speech movements. The model is a neural network whose components correspond to regions of the cerebral cortex and cerebellum, including premotor, motor, auditory, and…

Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

PubMed

de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

2014-05-01

Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.

PubMed

Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato

2017-01-29

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Virtual reality training improves balance function.

PubMed

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-09-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

Virtual reality training improves balance function

PubMed Central

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-01-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651

Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex.

PubMed

Villa, R F; Gorini, A; Hoyer, S

2006-11-01

The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

Neurotensin effect on Na+, K+-ATPase is CNS area- and membrane-dependent and involves high affinity NT1 receptor.

PubMed

López Ordieres, María Graciela; Rodríguez de Lores Arnaiz, Georgina

2002-11-01

We have previously shown that peptide neurotensin inhibits cerebral cortex synaptosomal membrane Na+, K+-ATPase, an effect fully prevented by blockade of neurotensin NT1 receptor by antagonist SR 48692. The work was extended to analyze neurotensin effect on Na+, K+-ATPase activity present in other synaptosomal membranes and in CNS myelin and mitochondrial fractions. Results indicated that, besides inhibiting cerebral cortex synaptosomal membrane Na+, K+-ATPase, neurotensin likewise decreased enzyme activity in homologous striatal membranes as well as in a commercial preparation obtained from porcine cerebral cortex. However, the peptide failed to alter either Na+, K+-ATPase activity in cerebellar synaptosomal and myelin membranes or ATPase activity in mitochondrial preparations. Whenever an effect was recorded with the peptide, it was blocked by antagonist SR 48692, indicating the involvement of the high affinity neurotensin receptor (NT1), as well as supporting the contention that, through inhibition of ion transport at synaptic membrane level, neurotensin plays a regulatory role in neurotransmission.

Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI.

PubMed

Kamagata, Koji; Motoi, Yumiko; Hori, Masaaki; Suzuki, Michimasa; Nakanishi, Atsushi; Shimoji, Keigo; Kyougoku, Shinsuke; Kuwatsuru, Ryohei; Sasai, Keisuke; Abe, Osamu; Mizuno, Yoshikuni; Aoki, Shigeki; Hattori, Nobutaka

2011-04-01

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD. Copyright © 2011 Wiley-Liss, Inc.

Cerebral Oxygenation of the Cortex and Striatum following Normobaric Hyperoxia and Mild Hypoxia in Rats by EPR Oximetry using Multi-Probe Implantable Resonators

PubMed Central

Hou, Huagang; Li, Hongbin; Dong, Ruhong; Mupparaju, Sriram; Khan, Nadeem; Swartz, Harold

2013-01-01

Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO2) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO2 was measured simultaneously in the cerebral cortex and striatum in the same rats before, during, and after normobaric hyperoxia and mild hypoxia challenges. The baseline mean tissue pO2 values (±SE) were not significantly different between the cortex and striatum. During 30 min of 100% O2 inhalation, a statistically significant increase in tissue pO2 of all four sites was observed, however, the tissue pO2 of the striatum area was significantly higher than in the forelimb area of the cortex. Brain pO2 significantly decreased from the baseline value during 15 min of 15% O2 challenge. No differences in the recovery of the cerebral cortex and striatum pO2 were observed when the rats were allowed to breathe 30% O2. It appears that EPR oximetry using implantable resonators can provide information on pO2 under the experimental conditions needed for such a study. The levels of pO2 that occurred in these experiments are readily resolvable by multi-site EPR oximetry with multi-probe resonators. In addition, the ability to simultaneously measure the pO2 in several areas of the brain provides important information that could potentially help differentiate the pO2 changes that can occur due to global or local mechanisms. PMID:21445770

Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2016-10-01

Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

PubMed

Herrera, Jose L; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M; Alonso, Rafael; Wandosell, Francisco G

2018-01-01

Different dietary ratios of n -6/ n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n -6/ n -3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n -3 and n -6 LC-PUFAs.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

PubMed Central

Herrera, Jose L.; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G.; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M.; Alonso, Rafael; Wandosell, Francisco G.

2018-01-01

Different dietary ratios of n−6/n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n−6/n−3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n−3 and n−6 LC-PUFAs. PMID:29740285

Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, J.E.; Matthews, P.S.

1984-09-01

Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum,more » cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.« less

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex.

PubMed

Shang, Yuan-Qi; Xie, Jun; Peng, Wei; Zhang, Jian; Chang, Da; Wang, Ze

2018-04-01

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn't produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Microscope-integrated quantitative analysis of intraoperative indocyanine green fluorescence angiography for blood flow assessment: first experience in 30 patients.

PubMed

Kamp, Marcel A; Slotty, Philipp; Turowski, Bernd; Etminan, Nima; Steiger, Hans-Jakob; Hänggi, Daniel; Stummer, Walter

2012-03-01

Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

PubMed

Boucetta, Soufiane; Montplaisir, Jacques; Zadra, Antonio; Lachapelle, Francis; Soucy, Jean-Paul; Gravel, Paul; Dang-Vu, Thien Thanh

2017-10-01

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Methylmercury poisoning in common marmosets--a study of selective vulnerability within the cerebral cortex.

PubMed

Eto, K; Yasutake, A; Kuwana, T; Korogi, Y; Akima, M; Shimozeki, T; Tokunaga, H; Kaneko, Y

2001-01-01

Neuropathological lesions found in chronic human Minamata disease tend to be localized in the calcarine cortex of occipital lobes, the pre- and postcentral lobuli, and the temporal gyri. The mechanism for the selective vulnerability is still not clear, though several hypotheses have been proposed. One hypothesis is vascular and postulates that the lesions are the result of ischemia secondary to compression of sulcal arteries from methylmercury-induced cerebral edema. To test this hypothesis, we studied common marmosets because the cerebrum of marmosets has 2 distinct deep sulci, the calcarine and Sylvian fissures. MRI analysis, mercury assays of tissue specimens, histologic and histochemical studies of the brain are reported and discussed. Brains sacrificed early after exposure to methylmercury showed high contents of methylmercury and edema of the cerebral white matter. These results may explain the selective cortical degeneration along the deep cerebral fissures or sulci.

A network of networks model to study phase synchronization using structural connection matrix of human brain

NASA Astrophysics Data System (ADS)

Ferrari, F. A. S.; Viana, R. L.; Reis, A. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.

2018-04-01

The cerebral cortex plays a key role in complex cortical functions. It can be divided into areas according to their function (motor, sensory and association areas). In this paper, the cerebral cortex is described as a network of networks (cortex network), we consider that each cortical area is composed of a network with small-world property (cortical network). The neurons are assumed to have bursting properties with the dynamics described by the Rulkov model. We study the phase synchronization of the cortex network and the cortical networks. In our simulations, we verify that synchronization in cortex network is not homogeneous. Besides, we focus on the suppression of neural phase synchronization. Synchronization can be related to undesired and pathological abnormal rhythms in the brain. For this reason, we consider the delayed feedback control to suppress the synchronization. We show that delayed feedback control is efficient to suppress synchronous behavior in our network model when an appropriate signal intensity and time delay are defined.

Truncated tyrosine kinase B brain-derived neurotrophic factor receptor directs cortical neural stem cells to a glial cell fate by a novel signaling mechanism.

PubMed

Cheng, Aiwu; Coksaygan, Turhan; Tang, Hongyan; Khatri, Rina; Balice-Gordon, Rita J; Rao, Mahendra S; Mattson, Mark P

2007-03-01

During development of the mammalian cerebral cortex neural stem cells (NSC) first generate neurons and subsequently produce glial cells. The mechanism(s) responsible for this developmental shift from neurogenesis to gliogenesis is unknown. Brain-derived neurotrophic factor (BDNF) is believed to play important roles in the development of the mammalian cerebral cortex; it enhances neurogenesis and promotes the differentiation and survival of newly generated neurons. Here, we provide evidence that a truncated form of the BDNF receptor tyrosine kinase B (trkB-t) plays a pivotal role in directing embryonic mouse cortical NSC to a glial cell fate. Expression of trkB-t promotes differentiation of NSC toward astrocytes while inhibiting neurogenesis both in cell culture and in vivo. The mechanism by which trkB-t induces astrocyte genesis is not simply the result of inhibition of full-length receptor with intrinsic tyrosine kinase activity signaling. Instead, binding of BDNF to trkB-t activates a signaling pathway (involving a G-protein and protein kinase C) that induced NSC to become glial progenitors and astrocytes. Thus, the increased expression of trkB-t in the embryonic cerebral cortex that occurs coincident with astrocyte production plays a pivotal role in the developmental transition from neurogenesis to gliogenesis. Our findings suggest a mechanism by which a single factor (BDNF) regulates the production of the two major cell types in the mammalian cerebral cortex.

Further studies on cortical tangential migration in wild type and Pax-6 mutant mice.

PubMed

Jiménez, D; López-Mascaraque, L; de Carlos, J A; Valverde, F

2002-01-01

In this study we present new data concerning the tangential migration from the medial and lateral ganglionic eminences (MGE and LGE) to the cerebral cortex during development. We have used Calbindin as a useful marker to follow the itinerary of tangential migratory cells during early developmental stages in wild-type and Pax-6 homozygous mutant mice. In the wild-type mice, at early developmental stages, migrating cells advance through the intermediate zone (IZ) and preplate (PP). At more advanced stages, migrating cells were present in the subplate (SP) and cortical plate (CP) to reach the entire developing cerebral cortex. We found that, in the homozygous mutant mice (Pax-6(Sey-Neu)/Pax-6(Sey-Neu)), this tangential migration is severely affected at early developmental stages: migrating cells were absent in the IZ, which were only found some days later, suggesting that in the mutant mice, there is a temporal delay in tangential migration. We have also defined some possible mechanisms to explain certain migratory routes from the basal telencephalon to the cerebral cortex. We describe the existence of two factors, which we consider to be essential for the normal migration; the first one is the cell adhesion molecule PSA-NCAM, whose role in other migratory systems is well known. The second factor is Robo-2, whose expression delimits a channel for the passage of migratory cells from the basal telencephalon to the cerebral cortex.

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

PubMed

Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of haptic information in the cerebral cortex

PubMed Central

2016-01-01

Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and top-down attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level. PMID:27440247

Receptors for VIP and PACAP in guinea pig cerebral cortex: effects on cyclic AMP synthesis and characterization by 125I-VIP binding.

PubMed

Zawilska, Jolanta B; Dejda, Agnieszka; Niewiadomski, Pawel; Gozes, Illana; Nowak, Jerzy Z

2005-01-01

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in guinea pig cerebral cortex were characterized by (1) radioreceptor binding of 125I-labeled VIP (human/rat/porcine), and (2) cyclic AMP (cAMP) formation. Saturation analysis of 125I-VIP binding to membranes of guinea pig cerebral cortex resulted in a linear Scatchard plot, suggesting the presence of a single class of high-affinity receptor-binding sites, with a Kd of 0.63 nM and a B(max) of 77 fmol/mg protein. Various peptides from the PACAP/VIP/secretin family displaced the specific binding of 125I-VIP to guinea pig cerebrum with the relative rank order of potency: chicken VIP (cVIP) > or = PACAP38 approximately PACAP27 approximately guinea pig VIP (gpVIP) > or = mammalian (human/rat/porcine) VIP (mVIP) > peptide histidine-methionine (PHM) > peptide histidine-isoleucine (PHI) > secretin. Analysis of the competition curves revealed displacement of 125I-VIP from high- and lower-affinity binding sites, with IC50 values in the picomolar and the nanomolar range, respectively. About 70% of the specific 125I-VIP-binding sites in guinea pig cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, cVIP, gpVIP, mVIP, PHM, and PHI stimulated cAMP production in [3H]adenine-prelabeled slices of guinea pig cerebral cortex in a concentration-dependent manner. Of the tested peptides, the most effective were PACAP38 and PACAP27, which at a 1 microM concentration produced a 17- to 19-fold rise in cAMP synthesis, increasing the nucleotide production to approx 11% conversion above the control value. The three forms of VIP (cVIP, mVIP, and gpVIP) at the highest concentration used, i.e., 3 microM, produced net increases in cAMP production in the range of 8-9% conversion, whereas 5 microM PHM and PHI, by, respectively, 6.7% and 4.9% conversion. It is concluded that cerebral cortex of guinea pig contains VPAC- type receptors positively linked to cAMP formation. In addition, the observed stronger action of PACAP (both PACAP38 and PACAP27), when compared to any form of VIP, on cAMP production in this tissue, suggests its interaction with both PAC1 and VPAC receptors.

Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

PubMed

Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

2010-05-31

Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

PubMed

Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Imagery use and affective responses during exercise: an examination of cerebral hemodynamics using near-infrared spectroscopy.

PubMed

Tempest, Gavin; Parfitt, Gaynor

2013-10-01

Imagery, as a cognitive strategy, can improve affective responses during moderate-intensity exercise. The effects of imagery at higher intensities of exercise have not been examined. Further, the effect of imagery use and activity in the frontal cortex during exercise is unknown. Using a crossover design (imagery and control), activity of the frontal cortex (reflected by changes in cerebral hemodynamics using near-infrared spectroscopy) and affective responses were measured during exercise at intensities 5% above the ventilatory threshold (VT) and the respiratory compensation point (RCP). Results indicated that imagery use influenced activity of the frontal cortex and was associated with a more positive affective response at intensities above VT, but not RCP to exhaustion (p < .05). These findings provide direct neurophysiological evidence of imagery use and activity in the frontal cortex during exercise at intensities above VT that positively impact affective responses.

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

PubMed

Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

2016-11-01

Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

The effect of donepezil on increased regional cerebral blood flow in the posterior cingulate cortex of a patient with Parkinson's disease dementia.

PubMed

Imamura, Keiko; Wada-Isoe, Kenji; Kowa, Hisanori; Tanabe, Yoshio; Nakashima, Kenji

2008-01-01

It has been reported that the cholinesterase inhibitor, donepezil, improves cognitive decline in patients with Parkinson's disease dementia (PDD). However, this improvement was dominant for frontal lobe dysfunction, and the increase in the Mini-Mental State Examination (MMSE) score was minimal. We report a PDD patient with a decline of regional cerebral blood flow (rCBF) in the posterior cingulate cortex, precunei, and bilateral parietotemporal association cortex, as determined by single-photon emission computed tomography (SPECT) using the easy Z-scores imaging system (e-ZIS). Upon administration of donepezil, both the rCBF and MMSE score increased. The effectiveness of donepezil may vary based on the rCBF pattern in PDD.

[Effect of nootropic agents on impulse activity of cerebral cortex neurons].

PubMed

Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

2001-01-01

The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

NASA Astrophysics Data System (ADS)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

[Research on activity evolution of cerebral cortex and hearing rehabilitation of congenitally deaf children after cochlear implant].

PubMed

Wang, X J; Liang, M J; Zhang, J P; Huang, H; Zheng, Y Q

2017-11-05

Objective: There is a significant difference in the hearing rehabilitation between the congenitally deaf children after cochlear implant(CI). The intrinsic mechanism that affects the hearing rehabilitation in patients was discussed from the perspective of evoked EEG source activity. Method: Firstly, we collected the ERP data from 23 patients and 10 control group children during 0, 3, 6, 9 and 12 months after CI. According to the hearing rehabilitation during 12 months after CI, the patients were divided into two groups: rehabilitation of "the good" and "the poor". Then we used sLORETA to show the changes in the groups of patients' cerebral cortex and compared with the control group. Result: Cross-modal reorganization of cerebral cortex exists in the congenitally deaf children. The cross-modal reorganization gradually degraded and the activity of the relevant cortex followed by normally after CI. There was a statistically significant difference( P < 0.05) in the temporal lobe and the associated cortex around parietal lobe between "the good" and "the poor" groups after 12 months. Conclusion: The normalization of the cross-modal reorganization in patients reflects the hearing rehabilitation after CI, especially the normalization of the activity of the temporal lobe and the associated cortex around parietal lobe, which influences the rehabilitation effect of the auditory function to some extent. This research demonstrated the detection of the mechanism has important significance for the hearing recovery training and evaluation of the hearing rehabilitation after CI. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

PubMed

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J; Smith, Conor; LaDu, Mary Jo; Sullivan, Patrick M; Morgan, Todd E; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olof; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E

2016-01-01

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral Myiasis Associated with Artificial Cranioplasty Flap: A Case Report.

PubMed

Giri, Sachin Ashok; Kotecha, Nitin; Giri, Deepali; Diyora, Batuk; Nayak, Naren; Sharma, Alok

2016-03-01

Cranioplasty is a commonly performed procedure for the repair of cranial defects. Various materials have been used for this procedure and have a good safety profile. Human cerebral myiasis is an exceedingly rare condition. It involves the invasion of live or dead human tissues by larvae of the insect species dipterous. We describe the first case of cerebral myiasis associated with an artificial cranioplasty bone flap. There was delayed cerebral cortex infestation of the species dipterous after cranioplasty with polymethyl methacrylate bone flap. The patient initially presented with an acute subdural hematoma and contaminated, comminuted frontal bone fracture that required craniectomy with interval cranioplasty at 3 months. Two years after the index procedure, the patient presented for neurosurgical follow-up because of 2 months of nonhealing ulcers and a foul smell emanating from the cranioplasty site, as well as acute onset of unilateral arm and leg weakness. Surgical exploration found live larvae invading the dura and cerebral cortex, an area that was thoroughly debrided with good outcomes for the patient. Cerebral myiasis can be managed via surgical and antibiotic therapy to obtain a good clinical outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

The anatomy and physiology of the ocular motor system.

PubMed

Horn, Anja K E; Leigh, R John

2011-01-01

Accurate diagnosis of abnormal eye movements depends upon knowledge of the purpose, properties, and neural substrate of distinct functional classes of eye movement. Here, we summarize current concepts of the anatomy of eye movement control. Our approach is bottom-up, starting with the extraocular muscles and their innervation by the cranial nerves. Second, we summarize the neural circuits in the pons underlying horizontal gaze control, and the midbrain connections that coordinate vertical and torsional movements. Third, the role of the cerebellum in governing and optimizing eye movements is presented. Fourth, each area of cerebral cortex contributing to eye movements is discussed. Last, descending projections from cerebral cortex, including basal ganglionic circuits that govern different components of gaze, and the superior colliculus, are summarized. At each stage of this review, the anatomical scheme is used to predict the effects of lesions on the control of eye movements, providing clinical-anatomical correlation. Copyright © 2011 Elsevier B.V. All rights reserved.

Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

NASA Astrophysics Data System (ADS)

Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

2013-06-01

Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

Spinal Cord Injury Causes Brain Inflammation Associated with Cognitive and Affective Changes: Role of Cell Cycle Pathways

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Stoica, Bogdan A.; Kumar, Alok; Luo, Tao; Skovira, Jacob; Faden, Alan I.

2014-01-01

Experimental spinal cord injury (SCI) causes chronic neuropathic pain associated with inflammatory changes in thalamic pain regulatory sites. Our recent studies examining chronic pain mechanisms after rodent SCI showed chronic inflammatory changes not only in thalamus, but also in other regions including hippocampus and cerebral cortex. Because changes appeared similar to those in our rodent TBI models that are associated with neurodegeneration and neurobehavioral dysfunction, we examined effects of mouse SCI on cognition, depressive-like behavior, and brain inflammation. SCI caused spatial and retention memory impairment and depressive-like behavior, as evidenced by poor performance in the Morris water maze, Y-maze, novel objective recognition, step-down passive avoidance, tail suspension, and sucrose preference tests. SCI caused chronic microglial activation in the hippocampus and cerebral cortex, where microglia with hypertrophic morphologies and M1 phenotype predominated. Stereological analyses showed significant neuronal loss in the hippocampus at 12 weeks but not 8 d after injury. Increased cell-cycle-related gene (cyclins A1, A2, D1, E2F1, and PCNA) and protein (cyclin D1 and CDK4) expression were found chronically in hippocampus and cerebral cortex. Systemic administration of the selective cyclin-dependent kinase inhibitor CR8 after SCI significantly reduced cell cycle gene and protein expression, microglial activation and neurodegeneration in the brain, cognitive decline, and depression. These studies indicate that SCI can initiate a chronic brain neurodegenerative response, likely related to delayed, sustained induction of M1-type microglia and related cell cycle activation, which result in cognitive deficits and physiological depression. PMID:25122899

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury

PubMed Central

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G.; Hovda, David A.; Sutton, Richard L.

2013-01-01

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients’ remains under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6 h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. PMID:23994447

Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.

PubMed

Chi, Nai-Fang; Liu, Ho-Ling; Yang, Jen-Tsung; Lin, Jr-Rung; Liao, Shu-Li; Peng, Bo-Han; Lee, Yen-Tung; Lee, Tsong-Hai

2014-01-01

BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.

The difference in the effect of glutamate and NO synthase inhibitor on free calcium concentration and Na+, K+-ATPase activity in synaptosomes from various brain regions.

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Leont'ev, V G

1999-09-01

The significant increase of free calcium concentration ([Ca2+]i) was found in rat cerebral cortex synaptosomes and hippocampal crude synaptosomal fraction after their exposure to glutamate. But no change of [Ca2+]i was revealed in cerebellar synaptosomes, the slight increase of [Ca2+]i in striatal synaptosomes was not significant. The presence of Ng-nitro-L-arginine methyl ester (L-NAME) in the incubation medium practically prevented the increase of [Ca2+]i initiated by glutamate in cerebral cortex synaptosomes, but not in hippocampal ones. The significant diminution of [Ca2+]i in the presence of this inhibitor was shown in striatal synaptosomes exposed to glutamate. Na+,K+-ATPase activity is significantly lower in cerebral cortex, striatal and hippocampal synaptosomes exposed to glutamate. L-NAME prevented the inactivation of this enzyme by glutamate. In cerebellar synaptosomes the tendency to the decrease of enzymatic activity in the presence of L-NAME was on the contrary noticed. Thus, the data obtained provide evidence of the protective effect of NO synthase inhibitor in brain cortex and striatal synaptosomes, but not in cerebellar synaptosomes. Synaptosomes appear to be an adequate model to study the regional differences in the mechanism of toxic effect of excitatory amino acids.

MRI-based morphometric characterizations of sexual dimorphism of the cerebrum of ferrets (Mustela putorius).

PubMed

Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

2013-12-01

The present study aimed to characterize cerebral morphology in young adult ferrets and its sexual dimorphism using high-field MRI and MRI-based morphometry. Ex vivo short TR/TE (typical T1-weighted parameter setting for conventional MRI) and T2W (long TR/TE) MRI with high spatial resolution at 7-tesla could visualize major subcortical and archicortical structures, i.e., the caudate nucleus, lentiform nucleus, amygdala and hippocampus. In particular, laminar organization of the olfactory bulb was identifiable by short TR/TE-MRI. The primary and secondary sulci observable in the adult ferret were distinguishable on either short TR/TE- or T2W-MRI, and the cortical surface morphology was reproduced well by 3D-rendered images obtained by short TR/TE-MRI. The cerebrum had a significantly lower volume in females than in males, which was attributed to region-specific volume reduction in the cerebral cortex and subcortical white matter in females. A sexual difference was also detected, manifested by an overall reduction in normalized signal ratios of short TR/TE-MRI in all cerebral structures examined in females than in males. On the other hand, an alternating array of higher and lower short TR/TE-MRI intensity transverse zones throughout the cortex, which was reminiscent of the functional cortical areas, was revealed by maximum intensity projection (MIP) in 3D. The normalized signal ratio of short TR/TE-MRI, but not T2W-MRI in the cortex, was negatively correlated with the density of myelin-basic protein immunoreactive fibers (males, r=-0.440; females, r=-0.481). The present results suggest that sexual differences in the adult ferret cerebrum are characterized by reduced volumes of the cerebral cortex and subcortical white matter in females, and by overall reductions in physiochemical characteristics, as obtained by short TR/TE-MRI, in females. It should be noted that short TR/TE-MRI-based MIP delineated functional cortical areas related to myeloarchitecture in 3D. Such an approach makes possible conventional investigation of the functional organization of the cerebral cortex and its abnormalities using high-field MRI. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

PubMed

Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

PubMed

Akinyemi, Ayodele Jacob; Okonkwo, Princess Kamsy; Faboya, Opeyemi Ayodeji; Onikanni, Sunday Amos; Fadaka, Adewale; Olayide, Israel; Akinyemi, Elizabeth Olufisayo; Oboh, Ganiyu

2017-02-01

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration after a small hemorrhage near the internal capsule in rats.

PubMed

Ueda, Yoshitomo; Masuda, Tadashi; Ishida, Akimasa; Misumi, Sachiyo; Shimizu, Yuko; Jung, Cha-Gyun; Hida, Hideki

2014-11-01

Intracerebral hemorrhage (ICH) can cause direct brain injury at the insult site and indirect damage in remote brain areas. Although a protective effect of melatonin (ML) has been reported for ICH, its detailed mechanisms and effects on remote brain injury remain unclear. To clarify the mechanism of indirect neuroprotection after ICH, we first investigated whether ML improved motor function after ICH and then examined the underlying mechanisms. The ICH model rat was made by collagenase injection into the left globus pallidus, adjacent to the internal capsule. ML oral administration (15 mg/kg) for 7 days after ICH resulted in significant recovery of motor function. Retrograde labeling of the corticospinal tract by Fluoro-Gold revealed a significant increase in numbers of positive neurons in the cerebral cortex. Immunohistological analysis showed that ML treatment induced no difference in OX41-positive activated microglia/macrophage at day 1 (D1) but a significant reduction in 8-hydroxydeoxyguanosin-positive cells at D7. Neutral red assay revealed that ML significantly prevented H2 O2 -induced cell death in cultured oligodendrocytes and astrocytes but not in neurons. Electrophysiological response in the cerebral cortex area where the number of Fluoro-Gold-positive cells was increased was significantly improved in ML-treated rats. These data suggest that ML improves motor abilities after ICH by protecting oligodendrocytes and astrocytes in the vicinity of the lesion in the corticospinal tract from oxidative stress and causes enhanced electrical responsiveness in the cerebral cortex remote to the ICH pathology. Copyright © 2014 Wiley Periodicals, Inc.

Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

PubMed

Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

2013-03-01

Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

Perinatal asphyxia results in changes in presynaptic bouton number in striatum and cerebral cortex-a stereological and behavioral analysis.

PubMed

Van de Berg, W D; Blokland, A; Cuello, A C; Schmitz, C; Vreuls, W; Steinbusch, H W; Blanco, C E

2000-10-01

Deficits in cognitive function have been related to quantitative changes in synaptic population, particularly in the cerebral cortex. Here, we used an established model of perinatal asphyxia that induces morphological changes, i.e. neuron loss in the cerebral cortex and striatum, as well as behavioural deficits. We hypothesized that perinatal asphyxia may lead to a neurodegenerative process resulting in cognitive impairment and altered presynaptic bouton numbers in adult rats. We studied cognitive performance at 18 months and presynaptic bouton numbers at 22 months following perinatal asphyxia. Data of the spatial Morris water escape task did not reveal clear memory or learning deficits in aged asphyctic rats compared to aged control rats. However, a memory impairment in aged rats versus young rats was observed, which was more pronounced in asphyctic rats. We found an increase in presynaptic bouton density in the parietal cortex, whereas no changes were found in striatum and frontal cortex in asphyctic rats. An increase of striatal volume was observed in asphyctic rats, leading to an increase in presynaptic bouton numbers in this area. These findings stress the issue that volume measurements have to be taken into account when determining presynaptic bouton density. Furthermore, perinatal asphyxia led to region-specific changes in presynaptic bouton numbers and it worsened the age-related cognitive impairment. These results suggest that perinatal asphyxia induced neuronal loss, which is compensated for by an increase in presynaptic bouton numbers.

The Neural Mechanism Exploration of Adaptive Motor Control: Dynamical Economic Cell Allocation in the Primary Motor Cortex.

PubMed

Li, Wei; Guo, Yangyang; Fan, Jing; Ma, Chaolin; Ma, Xuan; Chen, Xi; He, Jiping

2017-05-01

Adaptive flexibility is of significance for the smooth and efficient movements in goal attainment. However, the underlying work mechanism of the cerebral cortex in adaptive motor control still remains unclear. How does the cerebral cortex organize and coordinate the activity of a large population of cells in the implementation of various motor strategies? To explore this issue, single-unit activities from the M1 region and kinematic data were recorded simultaneously in monkeys performing 3D reach-to-grasp tasks with different perturbations. Varying motor control strategies were employed and achieved in different perturbed tasks, via the dynamic allocation of cells to modulate specific movement parameters. An economic principle was proposed for the first time to describe a basic rule for cell allocation in the primary motor cortex. This principle, defined as the Dynamic Economic Cell Allocation Mechanism (DECAM), guarantees benefit maximization in cell allocation under limited neuronal resources, and avoids committing resources to uneconomic investments for unreliable factors with no or little revenue. That is to say, the cells recruited are always preferentially allocated to those factors with reliable return; otherwise, the cells are dispatched to respond to other factors about task. The findings of this study might partially reveal the working mechanisms underlying the role of the cerebral cortex in adaptive motor control, wherein is also of significance for the design of future intelligent brain-machine interfaces and rehabilitation device.

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

PubMed

Sasaki, Kazumasu; Mutoh, Tatsushi; Nakamura, Kazuhiro; Kojima, Ikuho; Taki, Yasuyuki; Suarez, Jose Ignacio; Ishikawa, Tatsuya

2017-07-13

Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r 2 =0.31, P=0.0002). Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural and functional analyses of human cerebral cortex using a surface-based atlas

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.

1997-01-01

We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral Cortex in the Presence or Absence of Nitric Oxide Inhibition.

PubMed

Yarube, I U; Ayo, J O; Fatihu, M Y; Magaji, R A; Umar, I A; Alhassan, A W; Saleh, M Ia

2017-03-06

Insulin has emerged from its traditional 'peripheral' glucose-lowering function to become increasingly regarded as a brain hormone that controls a wide range of functions including learning and memory. Insulin action on learning and memory is linked to nitric oxide (NO) signalling, but its effects on memory and histology of cerebral cortex in conditions of varied NO availability is unclear. This research sought to determine the effect of insulin on visuo-spatial learning, memory and histology of cerebral cortex during NO deficiency. Twenty-four mice weighing 21-23 g, were divided into four groups (n = 6) and treated daily for seven days with 0.2 ml distilled water subcutaneously (s.c.) (control), 10 I.U/kg insulin s.c., 10 I.U/kg insulin + 50 mg/kg L-NAME intraperitoneally (i.p.), and 50 mg/kg i.p. L-NAME s.c., respectively. The 3-day MWM paradigm was used to assess memory. Brain tissue was examined for histological changes. There was no significant difference between day 1 and day 2 latencies for all the groups. The mice in all (but L-NAME) groups spent more time in the target quadrant, and the difference was significant within but not between groups. There was significant reduction in number of platform site crossings (4.83 ± 0.5, 0.67 ± 0.3, 0.50 ± 0.3 and 0.50 ± 0.3 for control, insulin, insulin+L-NAME and L-NAME groups, respectively) in all the groups compared to control. Normal histology of the cortex and absence of histological lesions were observed in brain slides of control and treatment groups. It was concluded that insulin administration impairs visuo-spatial memory to a greater extent in the presence of NO block, and to a lesser extent in the absence of NO block. Nitric oxide has a role in insulin-induced memory impairment. Insulin administration in the presence or absence of NO block had no effect on histology of cortex.

Modest changes in cerebral glucose metabolism in patients with sleep apnea syndrome after continuous positive airway pressure treatment.

PubMed

Ju, Gawon; Yoon, In-Young; Lee, Sang Don; Kim, Yu Kyeong; Yoon, Eunjin; Kim, Jeong-Whun

2012-01-01

Decreased cerebral glucose metabolism has been reported in patients with sleep apnea syndrome (SAS), but it has yet to be decided whether cerebral glucose metabolism in SAS can be altered by continuous positive airway pressure (CPAP) treatment. The aim of this study was to evaluate cerebral glucose metabolism changes in patients with SAS after CPAP treatment. Thirteen middle-aged male patients with severe SAS [mean age 49.3 ± 7.2 years, mean apnea-hypopnea index (AHI) 60.4 ± 21.2] and 13 male controls (mean age 46.0 ± 9.4 years, mean AHI 4.1 ± 3.7) participated in the study. All 26 study subjects underwent fluorodeoxyglucose-positron emission tomography (FDG-PET), but SAS patients underwent FDG-PET twice, namely before and 3 months after acceptable CPAP usage. Significant hypometabolism was observed in the bilateral prefrontal areas, left cuneus and left cingulate cortex of SAS patients before CPAP, and after CPAP, significant increases in cortical glucose metabolism were observed in the bilateral precentral gyri and left anterior cingulate cortex. However, these improvements in hypometabolism in both areas were insufficient to reach control levels, and hypometabolism in other regions persisted after CPAP treatment. Reduced cerebral glucose metabolism in the precentral gyrus and the cingulate cortex in patients with SAS was modestly improved by acceptable CPAP treatment. The findings of this study suggest that acceptable CPAP usage cannot completely reverse reduced cerebral glucose metabolism in SAS patients. Further studies are required to evaluate the long-term effects of CPAP treatment with total compliance. Copyright © 2012 S. Karger AG, Basel.

Local Circuit Inhibition in the Cerebral Cortex as the source of Gain Control and Untuned Suppression

PubMed Central

Shapley, Robert M.; Xing, Dajun

2012-01-01

Theoretical considerations have led to the concept that the cerebral cortex is operating in a balanced state in which synaptic excitation is approximately balanced by synaptic inhibition from the local cortical circuit. This paper is about the functional consequences of the balanced state in sensory cortex. One consequence is gain control: there is experimental evidence and theoretical support for the idea that local circuit inhibition acts as a local automatic gain control throughout the cortex. Second, inhibition increases cortical feature selectivity: many studies of different sensory cortical areas have reported that suppressive mechanisms contribute to feature selectivity. Synaptic inhibition from the local microcircuit should be untuned (or broadly tuned) for stimulus features because of the microarchitecture of the cortical microcircuit. Untuned inhibition probably is the source of Untuned Suppression that enhances feature selectivity. We studied inhibition’s function in our experiments, guided by a neuronal network model, on orientation selectivity in the primary visual cortex, V1, of the Macaque monkey. Our results revealed that Untuned Suppression, generated by local circuit inhibition, is crucial for the generation of highly orientation-selective cells in V1 cortex. PMID:23036513

Surface Based Analysis of Diffusion Orientation for Identifying Architectonic Domains in the In Vivo Human Cortex

PubMed Central

McNab, Jennifer A.; Polimeni, Jonathan R.; Wang, Ruopeng; Augustinack, Jean C.; Fujimoto, Kyoko; Player, Allison; Janssens, Thomas; Farivar, Reza; Folkerth, Rebecca D.; Vanduffel, Wim; Wald, Lawrence L.

2012-01-01

Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in grey matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical grey matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1. PMID:23247190

Alteration in 5-HT₂C, NMDA receptor and IP3 in cerebral cortex of epileptic rats: restorative role of Bacopa monnieri.

PubMed

Krishnakumar, Amee; Anju, T R; Abraham, Pretty Mary; Paulose, C S

2015-01-01

Bacopa monnieri is effective in stress management, brain function and a balanced mood. 5-HT2C receptors have been implicated in stress whereas NMDA receptors and mGlu5 play crucial role in memory and cognition. In the present study, we investigated the role of B. monnieri extract in ameliorating pilocarpine induced temporal lobe epilepsy through regulation of 5-HT2C and NMDA receptors in cerebral cortex. Our studies confirmed an increased 5-HT2C receptor function during epilepsy thereby facilitating IP3 release. We also observed an decreased NMDA receptor function with an elevated mGlu5 and GLAST gene expression in epileptic condition indicating the possibility for glutamate mediated excitotoxicity. These alterations lead to impaired behavioural functions as indicated by the Elevated Plus maze test. Carbamazepine and B. monnieri treatments to epileptic rats reversed the alterations in 5-HT2C, NMDA receptor functions and IP3 content thereby effectively managing the neurotransmitter balance in the cerebral cortex.

Compound of icariin, astragalus, and puerarin mitigates iron overload in the cerebral cortex of Alzheimer's disease mice.

PubMed

Zhang, Yu; Kong, Wei-Na; Chai, Xi-Qing

2018-04-01

Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer's disease. Icariin, astragalus, and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer's disease mice, although the underlying mechanism remains unclear. In the present study, APPswe/PS1ΔE9 transgenic mice were administered icariin, astragalus, and puerarin (120, 80, and 80 mg/kg, respectively, once a day, for 3 months). Iron levels were detected by flame atomic absorption spectroscopy. Interleukin-1β, interleukin-6, and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay. Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry. Our results demonstrate that after treatment, iron levels and malondialdehyde content are decreased, while glutathione peroxidase and superoxide dismutase activities are increased. Further, interleukin-1β, interleukin-6, and tumor necrosis factor-α levels were reduced. These results confirm that compounds of icariin, astragalus, and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.

Difference of language cortex reorganization between cerebral arteriovenous malformations, cavernous malformations, and gliomas: a functional MRI study.

PubMed

Deng, Xiaofeng; Xu, Long; Zhang, Yan; Wang, Bo; Wang, Shuo; Zhao, Yuanli; Cao, Yong; Zhang, Dong; Wang, Rong; Ye, Xun; Wu, Jun; Zhao, Jizong

2016-04-01

The authors attempted to demonstrate the difference in language cortex reorganization between cerebral malformations (AVMs), cavernous malformations (CMs), and gliomas by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Clinical and imaging data of 27 AVM patients (AVM-L group), 29 CM patients (CM-L group), and 20 glioma patients (Glioma-L group) were retrospectively reviewed, with lesions overlying the left inferior frontal gyrus (Broca area). As a control, patients with lesions involving the right inferior frontal gyrus were also enrolled, including 14 AVM patients (AVM-R group), 20 CM patients (CM-R group), and 14 glioma patients (Glioma-R group). All patients were right-handed. Lateralization indices (LI) of BOLD signal activations were calculated separately for Broca and Wernicke areas. In AVM-L group, right-sided lateralization of BOLD signals was observed in 10 patients (37.0%), including 6 in the Broca area alone, 1 in the Wernicke area alone, and 3 in both areas. Three patients (10.3%) of CM-L group showed right-sided lateralization in both Broca and Wernicke areas, and 1 patient (5.0%) of Glioma-L group had right-sided lateralization in the Wernicke area alone. A significant difference of right-sided lateralization was observed between the AVM-L group and CM-L group (P = 0.018) and also between the AVM-L group and Glioma-L group (P = 0.027). No patient in AVM-R, CM-R, or Glioma-R groups showed right-sided lateralization. Language cortex reorganization may occur in AVM, CM, and glioma patients when the traditional language cortex was involved by lesions, but the potential of reorganization for CM and glioma patients seems to be insufficient compared with AVM patients.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Cell Type-Specific Circuit Mapping Reveals the Presynaptic Connectivity of Developing Cortical Circuits

PubMed Central

Cocas, Laura A.; Fernandez, Gloria; Barch, Mariya; Doll, Jason; Zamora Diaz, Ivan

2016-01-01

The mammalian cerebral cortex is a dense network composed of local, subcortical, and intercortical synaptic connections. As a result, mapping cell type-specific neuronal connectivity in the cerebral cortex in vivo has long been a challenge for neurobiologists. In particular, the development of excitatory and inhibitory interneuron presynaptic input has been hard to capture. We set out to analyze the development of this connectivity in the first postnatal month using a murine model. First, we surveyed the connectivity of one of the earliest populations of neurons in the brain, the Cajal-Retzius (CR) cells in the neocortex, which are known to be critical for cortical layer formation and are hypothesized to be important in the establishment of early cortical networks. We found that CR cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We also found that both excitatory pyramidal neurons and inhibitory interneurons received broad inputs in the first postnatal week, including inputs from CR cells. Expanding our analysis into the more mature brain, we assessed the inputs onto inhibitory interneurons and excitatory projection neurons, labeling neuronal progenitors with Cre drivers to study discrete populations of neurons in older cortex, and found that excitatory cortical and subcortical inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period. Cell type-specific circuit mapping is specific, reliable, and effective, and can be used on molecularly defined subtypes to determine connectivity in the cortex. SIGNIFICANCE STATEMENT Mapping cortical connectivity in the developing mammalian brain has been an intractable problem, in part because it has not been possible to analyze connectivity with cell subtype precision. Our study systematically targets the presynaptic connections of discrete neuronal subtypes in both the mature and developing cerebral cortex. We analyzed the connections that Cajal-Retzius cells make and receive, and found that these cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We assessed the inputs onto inhibitory interneurons and excitatory projection neurons, the major two types of neurons in the cortex, and found that excitatory inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period. PMID:26985044

Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice.

PubMed

Hotta, Harumi; Uchida, Sae; Kagitani, Fusako; Maruyama, Naoki

2011-05-01

We examined whether activity of the nucleus basalis of Meynert (NBM) regulates regional cerebral cortical blood flow (rCBF) in mice, using laser speckle and laser Doppler flowmetry. In anesthetized mice, unilateral focal stimulation, either electrical or chemical, of the NBM increased rCBF of the ipsilateral cerebral cortex in the frontal, parietal and occipital lobes, independent of changes in systemic blood pressure. Most of vasodilative responses to low intensity stimuli (2 times threshold intensity: 2T) were abolished by atropine (a muscarinic cholinergic blocker), whereas responses to higher intensity stimuli (3T) were abolished by atropine and mecamylamine (a nicotinic cholinergic blocker). Blood flow changes were largest when the tip of the electrode was located within the area containing cholinergic neurons shown by choline acetyltransferase-immunocytochemistry. These results suggest that cholinergic projections from basal forebrain neurons in mice cause vasodilation in the ipsilateral cerebral cortex by a combination of muscarinic and nicotinic mechanisms, as previously found in rats and cats.

Prenatal neurogenesis in autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kaushik, Gaurav; Zarbalis, Konstantinos

2016-03-01

An ever-increasing body of literature describes compelling evidence that a subset of young children on the autism spectrum show abnormal cerebral growth trajectories. In these cases, normal cerebral size at birth is followed by a period of abnormal growth and starting in late childhood often by regression compared to unaffected controls. Recent work has demonstrated an abnormal increase in the number of neurons of the prefrontal cortex suggesting that cerebral size increase in autism is driven by excess neuronal production. In addition, some affected children display patches of abnormal laminar positioning of cortical projection neurons. As both cortical projection neuron numbers and their correct layering within the developing cortex requires the undisturbed proliferation of neural progenitors, it appears that neural progenitors lie in the center of the autism pathology associated with early brain overgrowth. Consequently, autism spectrum disorders associated with cerebral enlargement should be viewed as birth defects of an early embryonic origin with profound implications for their early diagnosis, preventive strategies, and therapeutic intervention.

Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids

PubMed Central

Kellogg, Carol K.; Kenjarski, Thomas P.; Pleger, Gloria L.; Frye, Cheryl A.

2013-01-01

Fetal exposure to diazepam (DZ), a positive modulator of GABAA receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABAA receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.5 mg/kg) or the vehicle. Male and female offspring were analyzed at five postnatal ages. The levels of progesterone (P), dihydroprogesterone (DHP), 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), testosterone (T), dihydrotestosterone, and 5α-androstan-3α,17β diol were measured in the cerebral cortex and diencephalon. The results indicated that development of brain steroid levels and the impact of fetal DZ exposure were region- and sex-specific. Age-related changes in brain steroids did not mirror associated changes in circulating P and T. Age regulated the levels of all 3 progestins in the cerebral cortex, and fetal DZ exposure interacted with the development of P and DHP. The development of 3α,5α-THP in the cortex was markedly influenced by sex, with levels in males decreasing over postnatal development whereas they increased over postpubertal development in females. An adolescent surge in T levels was observed in male cortex and fetal DZ exposure prevented that surge. Steroid levels in the diencephalon were altered by age mainly in females, and DZ exposure had little effect in this region. The data support region-specific regulation of brain steroid synthesis. Only in the cerebral cortex are relevant mechanisms readily modifiable by fetal DZ exposure. However, neither sex nor fetal DZ exposure altered the response of GABAA receptors in adult cortex to neurosteroid. PMID:16376310

Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

PubMed

Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

2014-01-01

Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

Ethanol fixed brain imaging by phase-contrast X-ray technique

NASA Astrophysics Data System (ADS)

Takeda, Tohoru; Thet-Thet-Lwin; Kunii, Takuya; Sirai, Ryota; Ohizumi, Takahito; Maruyama, Hiroko; Hyodo, Kazuyuki; Yoneyama, Akio; Ueda, Kazuhiro

2013-03-01

The two-crystal phase-contrast X-ray imaging technique using an X-ray crystal interferometer can depict the fine structures of rat's brain such as cerebral cortex, white matter, and basal ganglia. Image quality and contrast by ethanol fixed brain showed significantly better than those by usually used formalin fixation at 35 keV X-ray energy. Image contrast of cortex by ethanol fixation was more than 3-times higher than that by formalin fixation. Thus, the technique of ethanol fixation might be better suited to image cerebral structural detail at 35 keV X-ray energy.

Deriving excitatory neurons of the neocortex from pluripotent stem cells

PubMed Central

Hansen, David V.; Rubenstein, John L.R.; Kriegstein, Arnold R.

2011-01-01

The human cerebral cortex is an immensely complex structure that subserves critical functions that can be disrupted in developmental and degenerative disorders. Recent innovations in cellular reprogramming and differentiation techniques have provided new ways to study the cellular components of the cerebral cortex. Here we discuss approaches to generate specific subtypes of excitatory cortical neurons from pluripotent stem cells. We review spatial and temporal aspects of cortical neuron specification that can guide efforts to produce excitatory neuron subtypes with increased resolution. Finally, we discuss distinguishing features of human cortical development and their translational ramifications for cortical stem cell technologies. PMID:21609822

Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model

PubMed Central

Zhou, Liang; Zhang, Jie; Wang, Chao; Sun, Qiangsan

2017-01-01

We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score (P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN (P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio (P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 (P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo. PMID:28402151

Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model.

PubMed

Zhou, Liang; Zhang, Jie; Wang, Chao; Sun, Qiangsan

2017-06-01

We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score ( P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN ( P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio ( P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 ( P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo.

Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-13C]Glucose and [1,2-13C]Acetate as Substrates.

PubMed

McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B; Andersen, Jens V; Aldana, Blanca I; Nissen, Jakob D; Schousboe, Arne; Waagepetersen, Helle S

2017-03-01

Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design. Cerebral cortical and hippocampal slices prepared from 16 to 18-week-old mice were incubated for 15-90 min with unlabeled glucose in combination with [U- 13 C]glucose or [1,2- 13 C]acetate. Our newly developed incubation apparatus allows accurate control of temperature and is designed to avoid evaporation of the incubation medium. Subsequent to incubation, slices were extracted and extracts analyzed for 13 C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation media. Based on the measured 13 C-labeling (%), total amino acid contents and relative activity of metabolic enzymes/pathways, we conclude that the slice preparations in the current incubation apparatus exhibited a high degree of metabolic integrity. Comparison of 13 C-labeling observed with [U- 13 C]glucose in slices from cerebral cortex and hippocampus revealed no significant regional differences regarding glycolytic or total TCA cycle activities. On the contrary, results from the incubations with [1,2- 13 C]acetate suggest a higher capacity of the astrocytic TCA cycle in hippocampus compared to cerebral cortex. Finally, we propose a new approach for assessing compartmentation of metabolite pools between astrocytes and neurons using 13 C-labeling (%) data obtained from mass spectrometry. Based on this approach we suggest that cellular metabolic compartmentation in hippocampus and cerebral cortex is very similar.

Blood -brain barrier disruption was less under isoflurane than pentobarbital anesthesia via a PI3K/Akt pathway in early cerebral ischemia.

PubMed

Chi, Oak Z; Mellender, Scott J; Kiss, Geza K; Liu, Xia; Weiss, Harvey R

2017-05-01

One of the important factors altering the degree of blood-brain barrier (BBB) disruption in cerebral ischemia is the anesthetic used. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been reported to be involved in modulating BBB permeability and in isoflurane induced neuroprotection. This study was performed to compare the degree of BBB disruption in focal cerebral ischemia under isoflurane vs pentobarbital anesthesia and to determine whether inhibition of PI3K/Akt would affect the disruption in the early stage of focal cerebral ischemia. Permanent middle cerebral artery (MCA) occlusion was performed in rats under 1.4% isoflurane or pentobarbital (50mg/kg i.p.) anesthesia with controlled ventilation. In half of each group LY294002, which is a PI3K/Akt inhibitor, was applied on the ischemic cortex immediately after MCA occlusion. After one hour of MCA occlusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB) was determined to quantify the degree of BBB disruption. MCA occlusion increased the K i both in the isoflurane and pentobarbital anesthetized rats. However, the value of K i was lower under isoflurane (11.5±6.0μL/g/min) than under pentobarbital (18.3±7.1μL/g/min) anesthesia. The K i of the contralateral cortex of the pentobarbital group was higher (+74%) than that of the isoflurane group. Application of LY294002 on the ischemic cortex increased the K i (+99%) only in the isoflurane group. The degree of BBB disruption by MCA occlusion was significantly lower under isoflurane than pentobarbital anesthesia in the early stage of cerebral ischemia. Our data demonstrated the importance of choice of anesthetics and suggest that PI3K/Akt signaling pathway plays a significant role in altering BBB disruption in cerebral ischemia during isoflurane but not during pentobarbital anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice.

PubMed

Thakare, Vishnu N; Patil, Rajesh R; Oswal, Rajesh J; Dhakane, Valmik D; Aswar, Manoj K; Patel, Bhoomika M

2018-02-01

Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress. The mice were subjected to CUMS for 28 days (4 weeks) and administered with silymarin (100 mg/kg and 200 mg/kg), or fluoxetine or vehicle from days 8 to 28 (3 weeks simultaneously). Animals were evaluated for behavioral changes, such as anhedonia by sucrose preference test, behavioral despair by forced swim test, and exploratory behaviors by an open field test. In addition, neurobiochemical alterations, mainly monoamines, 5-HT, NE, DA, neurotrophic factor BDNF, and cytokines, IL-6, TNF-α, oxidant-antioxidant parameters by determining the malondialdehyde formation (an index of lipid peroxidation process), superoxide dismutase (SOD) and catalase (CAT) activity in hippocampus and cerebral cortex along with serum corticosterone were investigated. Our findings reveal that mice subjected to CUMS exhibited lower sucrose preference, increase immobility time without affecting general locomotion of the animals, and reduce BDNF, 5-HT, NE, and DA level, increased serum corticosterone, IL-6 and TNF-α along with an oxidant-antioxidant imbalance in the hippocampus and cerebral cortex. Silymarin significantly reversed the CUMS-induced changes in the hippocampus and cerebral cortex in mice. Thus, the possible mechanism involved in the antidepressant-like activity of silymarin is correlated to the alleviation of monoaminergic, neurogenesis (enhancing 5-HT, NE, and BDNF levels), and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus.

Bacopa monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia.

PubMed

Piyabhan, Pritsana; Wannasiri, Supaporn; Naowaboot, Jarinyaporn

2016-12-01

Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups for cognitive enhancement effect study: Group 1, Control; Group 2, PCP administration; Group 3, PCP+Brahmi. A neuroprotective-effect study was also carried out. Rats were again assigned to three groups: Group 1, Control; Group 2, PCP administration; Group 3, Brahmi+PCP. Discrimination ratio (DR) representing cognitive ability was obtained from a novel object recognition task. VGLUT3 immunodensity was measured in the prefrontal cortex, striatum and cornu ammonis fields 1-3 (CA1-3) using immunohistochemistry. We found reduced DR in the PCP group, which occurred alongside VGLUT3 reduction in all brain areas. PCP+Brahmi showed higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex and striatum. Brahmi+PCP group showed a higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex, striatum and CA1-3. We concluded that reduced cerebral VGLUT3 was involved in cognitive deficit in PCP-administrated rats. Receiving Brahmi after PCP restored cognitive deficit by increasing VGLUT3 in the prefrontal cortex and striatum. Receiving Brahmi before PCP prevented cognitive impairment by elevating VGLUT3 in prefrontal cortex, striatum and CA1-3. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia. © 2016 John Wiley & Sons Australia, Ltd.

Cognitive-motor interactions of the basal ganglia in development

PubMed Central

Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

2014-01-01

Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norton, S.; Kimler, B.F.

1988-07-01

Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (negative geotaxis, reflex suspension, continuous corridor and gait) were most affected by irradiation gestational day 15, as was body weight. When a lower dose of radiation (0.75 Gy) was used on gestational day 15, the damage to the cortex was much less but behavioralmore » changes were still present. Frontal, parietal and occipital areas of the cortex were approximately equally affected. Using stepwise multiple regression analysis, the linkage of functional tests and cortical thickness was examined. Functional variables which were most commonly included as predictors of frontal and parietal cortex were negative geotaxis and continuous corridor. Occipital cortical layers were not predicted by behavioral variables. In predicting function using cortical variables, frontal cortex was better than parietal and occipital cortex was the poorest predictor.« less

Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.

PubMed

Mao, Lun-Lin; Hao, Dong-Lin; Mao, Xiao-Wei; Xu, Yuan-Feng; Huang, Ting-Ting; Wu, Bo-Na; Wang, Li-Hui

2015-08-18

PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK-3β pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-α concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3β proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys.

PubMed

Muntané, Gerard; Santpere, Gabriel; Verendeev, Andrey; Seeley, William W; Jacobs, Bob; Hopkins, William D; Navarro, Arcadi; Sherwood, Chet C

2017-09-01

Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex. Although the overall pattern of gene expression was very similar between hemispheres in both humans and macaques, weighted gene correlation network analysis revealed gene co-expression modules associated with hemisphere, which are different among the three cortical regions examined. Notably, a receptor-enriched gene module in STC was particularly associated with hemisphere and showed different expression levels between hemispheres only in humans.

Human cortical–hippocampal dialogue in wake and slow-wave sleep

PubMed Central

Mitra, Anish; Hacker, Carl D.; Pahwa, Mrinal; Tagliazucchi, Enzo; Laufs, Helmut; Leuthardt, Eric C.; Raichle, Marcus E.

2016-01-01

Declarative memory consolidation is hypothesized to require a two-stage, reciprocal cortical–hippocampal dialogue. According to this model, higher frequency signals convey information from the cortex to hippocampus during wakefulness, but in the reverse direction during slow-wave sleep (SWS). Conversely, lower-frequency activity propagates from the information “receiver” to the “sender” to coordinate the timing of information transfer. Reversal of sender/receiver roles across wake and SWS implies that higher- and lower-frequency signaling should reverse direction between the cortex and hippocampus. However, direct evidence of such a reversal has been lacking in humans. Here, we use human resting-state fMRI and electrocorticography to demonstrate that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cerebral cortex. Moreover, both δ activity and infraslow activity reverse propagation directions between the hippocampus and cerebral cortex across wake and SWS. These findings provide direct evidence for state-dependent reversals in human cortical–hippocampal communication. PMID:27791089

[A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis co-occurring with unilateral cerebral cortical encephalitis].

PubMed

Fukushima, Naoya; Suzuki, Miki; Ogawa, Ryo; Hayashi, Kitami; Takanashi, Jun-Ichi; Ohashi, Takashi

2017-11-25

A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM) at 11 years of age. At 17 years of age, she was hospitalized due to generalized seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she was admitted to our hospital, diagnosed with multifocal disseminated encephalomyelitis (MDEM). MDEM has been observed in patients that are seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex encephalitis with epilepsy has also been reported in such patients. The co-occurrence of MDEM and cortical encephalitis in the same patient has important implications for the pathogenesis of anti-MOG antibody-associated autoimmune diseases.

Modeling Early Cortical Serotonergic Deficits in Autism

PubMed Central

Boylan, Carolyn B.; Blue, Mary E.; Hohmann, Christine F.

2007-01-01

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas. PMID:17034875

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

PubMed

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2013-10-16

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

Modeling early cortical serotonergic deficits in autism.

PubMed

Boylan, Carolyn B; Blue, Mary E; Hohmann, Christine F

2007-01-10

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

Exercise-induced changes in local cerebral glucose utilization in the rat.

PubMed

Vissing, J; Andersen, M; Diemer, N H

1996-07-01

In exercise, little is known about local cerebral glucose utilization (LCGU), which is an index of functional neurogenic activity. We measured LCGU in resting and running (approximately 85% of maximum O2 uptake) rats (n = 7 in both groups) previously equipped with a tail artery catheter. LCGU was measured quantitatively from 2-deoxy-D-[1-14C]glucose autoradiographs. During exercise, total cerebral glucose utilization (TCGU) increased by 38% (p < 0.005). LCGU increased (p < 0.05) in areas involved in motor function (motor cortex 39%, cerebellum approximately 110%, basal ganglia approximately 30%, substantia nigra approximately 37%, and in the following nuclei: subthalamic 47%, posterior hypothalamic 74%, red 61%, ambiguous 43%, pontine 61%), areas involved in sensory function (somatosensory 27%, auditory 32%, and visual cortex 42%, thalamus approximately 75%, and in the following nuclei: Darkschewitsch 22%, cochlear 51%, vestibular 30%, superior olive 23%, cuneate 115%), areas involved in autonomic function (dorsal raphe nucleus 30%, and areas in the hypothalamus approximately 35%, amygdala approximately 35%, and hippocampus 29%), and in white matter of the corpus callosum (36%) and cerebellum (52%). LCGU did not change with exercise in prefrontal and frontal cortex, cingulum, inferior olive, nucleus of solitary tract and median raphe, lateral septal and interpenduncular nuclei, or in areas of the hippocampus, amygdala, and hypothalamus. Glucose utilization did not decrease during exercise in any of the studied cerebral regions. In summary, heavy dynamic exercise increases TCGU and evokes marked differential changes in LCGU. The findings provide clues to the cerebral areas that participate in the large motor, sensory, and autonomic adaptation occurring in exercise.

Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla.

PubMed

Yang, Jehoon; Shen, Jun

2006-09-01

The significance of changes in cerebral oxygen consumption in focally activated brain tissue is still controversial. Since the rate of cerebral oxygen consumption is tightly coupled to that of tricarboxylic acid cycle which can be measured from the turnover kinetics of [4-(13)C]glutamate using in vivo (1)H{(13)C} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle flux rate were assessed in primary somatosensory cortex of alpha-chloralose anesthetized rats during electrical forepaw stimulation. With markedly improved (1)H{(13)C} magnetic resonance spectroscopy technique and the use of high magnetic field strength of 11.7 T accessible to the current study, [4-(13)C]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances of [4-(13)C]glutamine at 2.46 ppm and [2-(13)C]GABA at 2.28 ppm as well as the more distal [3-(13)C]glutamate and [3-(13)C]glutamine. The results showed a significantly increased V(TCA) in focally activated primary somatosensory cortex during forepaw stimulation, corresponding to approximately 51 +/- 27% (n = 6, mean +/- SD) increase in cerebral oxygen consumption rate. Considering the high efficiency in producing adenosine triphosphate by oxidative metabolism of glucose, the results demonstrate that aerobic oxidative metabolism provides the majority of energy required for cerebral focal activation in alpha-chloralose anesthetized rats subjected to forepaw stimulation.

[Changes in pain sensitivity after the ablation of the somatosensory areas of the cerebral cortex in cats].

PubMed

Reshetniak, V K; Kukushkin, M L

1986-12-01

The effects of ablation of the first and second somatosensory cortex on pain sensitivity were studied in the behavioural experiments on adult cats. The ablation of the first somatosensory cortex (SI) was shown to cause an increase of the response thresholds at all the levels of a conventional scale, while the destruction of the second somatosensory cortex (S2) decreased the response thresholds. The role of SI and S2 in the evaluation of nociceptive information is discussed.

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Brain region differences in regulation of Akt and GSK3 by chronic stimulant administration in mice.

PubMed

Mines, Marjelo A; Jope, Richard S

2012-07-01

Acute amphetamine administration activates glycogen synthase kinase-3 (GSK3) by reducing its inhibitory serine-phosphorylation in mouse striatum and cerebral cortex. This results from Akt inactivation and is required for certain behavioral effects of amphetamine, such as increased locomotor activity. Here we tested if regulation of Akt and GSK3 was similarly affected by longer-term administration of amphetamine, as well as of methylphenidate, since each of these is administered chronically in patients with attention deficit hyperactivity disorder (ADHD). Akt is activated by post-translational phosphorylation on Thr308, and modulated by Ser473 phosphorylation, whereas phosphorylation on Ser21/9 inhibits the two GSK3 isoforms, GSK3α and GSK3β. After eight days of amphetamine or methylphenidate treatment, striatal Akt and GSK3 were dephosphorylated similar to reported changes after acute amphetamine treatment. Oppositely, in the cerebral cortex and hippocampus Akt and GSK3 phosphorylation increased after eight days of amphetamine or methylphenidate treatment. These opposite brain region changes in Akt and GSK3 phosphorylation matched opposite changes in the association of Akt with β-arrestin and GSK3, which after eight days of amphetamine treatment were increased in the striatum and decreased in the cerebral cortex. Thus, whereas the acute dephosphorylating effect of stimulants on Akt and GSK3 in the striatum was maintained, the response switched in the cerebral cortex after eight days of amphetamine or methylphenidate treatment to cause increased phosphorylation of Akt and GSK3. These results demonstrate that prolonged administration of stimulants causes brain region-selective differences in the regulation of Akt and GSK3. Copyright © 2012 Elsevier Inc. All rights reserved.

Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure.

PubMed

de Souza Machado, Fernanda; Kuo, Jonnsin; Wohlenberg, Mariane Farias; da Rocha Frusciante, Marina; Freitas, Márcia; Oliveira, Alice S; Andrade, Rodrigo B; Wannmacher, Clovis M D; Dani, Caroline; Funchal, Claudia

2016-12-01

Acai has been used by the population due to its high nutritional value and its benefits to health, such as its antioxidant properties. The aim of this study was to evaluate the protective effect of acai frozen pulp on oxidative stress parameters in cerebral cortex, hippocampus and cerebellum of Wistar rats treated with carbon tetrachloride (CCl 4 ). Thirty male Wistar rats (90-day-old) were orally treated with water or acai frozen pulp for 14 days (7 μL/g). On the 15th day, half of the animals received treatment with mineral oil and the other half with CCl 4 (3.0 mL/kg). The cerebral cortex, hippocampus and cerebellum were dissected and used for analysis of creatine kinase activity (CK), thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, and the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Statistical analysis was performed by ANOVA followed by Tukey's post-test. CCl 4 was able to inhibit CK activity in all tissues tested and to provoke lipid damage in cerebral cortex and cerebellum, and protein damage in the three tissues tested. CCl 4 enhanced CAT activity in the cerebral cortex, and inhibited CAT activity in the hippocampus and cerebellum and reduced SOD activity in all tissues studied. Acai frozen pulp prevented the inhibition of CK, TBARS, carbonyl and CAT activity in all brain structures and only in hippocampus for SOD activity. Therefore, acai frozen pulp has antioxidant properties and maybe could be useful in the treatment of some diseases that affect the central nervous system that are associated with oxidative damage.

The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

PubMed

Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

2011-01-25

Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission.

PubMed

L'Heureux, R; Dennis, T; Curet, O; Scatton, B

1986-06-01

The release of endogenous noradrenaline was measured in the cerebral cortex of the halothane-anesthetized rat by using the technique of brain dialysis coupled to a radioenzymatic assay. A thin dialysis tube was inserted transversally in the cerebral cortex (transcortical dialysis) and perfused with Ringer medium (2 microliter min-1). Under basal conditions, the cortical output of noradrenaline was stable over a period of at least 6 h and amounted to 8.7 pg/20 min (not corrected for recovery). Histological control of the perfused area revealed very little damage and normal morphology in the vicinity of the dialysis tube. Omission of calcium from the perfusion medium caused a marked drop in cortical noradrenaline output. Bilateral electrical stimulation (for 10 min) of the ascending noradrenergic pathways in the medial forebrain bundle caused a frequency-dependent increase in cortical noradrenaline output over the range 5-20 Hz. Stimulation at a higher frequency (50 Hz) resulted in a levelling off of the increase in cortical noradrenaline release. Systemic administration of the dopamine-beta-hydroxylase inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA 63) (25 mg/kg i.p.) markedly reduced, whereas injection of the monoamine oxidase inhibitor pargyline (75 mg/kg i.p.) resulted in a progressive increase in, cortical noradrenaline output. d-Amphetamine (2 mg/kg i.p.) provoked a sharp increase in cortical noradrenaline release (+450% over basal values within 40 min). Desmethylimipramine (10 mg/kg i.p.) produced a twofold increase of cortical noradrenaline release. Finally, idazoxan (20 mg/kg i.p.) and clonidine (0.3 mg/kg i.p.), respectively, increased and decreased the release of noradrenaline from the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

PubMed Central

García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis

2016-01-01

The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease. PMID:27847469

[Origin of cortical interneurons: basic concepts and clinical implications].

PubMed

Marín, O

Introduction and development. GABAergic interneurons play a prominent role in the function of the cerebral cortex, since they allow the synchronization of pyramidal neurons and greatly influence their differentiation and maturation during development. Until recently it has been thought that cortical interneurons and pyramidal neurons originate from progenitor cells located in the dorsal region of the telencephalon, the pallium. Recent studies, however, have demonstrated that a large number of cortical GABAergic neurons arise from progenitors located in the subpallium the region of the telencephalon that gives rise to the basal ganglia, and that they arise in the cerebral cortex after a long tangential migration. Aims. In this review I have summarized our current knowledge of the factors that control the specification of cortical interneurons, as well as the mechanisms that direct their migration to the cortex.

An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Niladri; Department of Natural Resource Sciences, McGill University, Ste.-Anne-de-Bellevue, Quebec, H9X 3V9; Stamler, Christopher J.

2005-05-15

Mercury (Hg) is a ubiquitous pollutant that can disrupt neurochemical signaling pathways in mammals. It is well documented that inorganic Hg (HgCl{sub 2}) and methyl Hg (MeHg) can inhibit the binding of radioligands to the muscarinic acetylcholine (mACh) receptor in rat brains. However, little is known concerning this relationship in specific anatomical regions of the brain or in other species, including humans. The purpose of this study was to explore the inhibitory effects of HgCl{sub 2} and MeHg on [{sup 3}H]-quinuclidinyl benzilate ([{sup 3}H]-QNB) binding to the mACh receptor in the cerebellum and cerebral cortex regions from human, rat, mouse,more » mink, and river otter brain tissues. Saturation binding curves were obtained from each sample to calculate receptor density (B {sub max}) and ligand affinity (K {sub d}). Subsequently, samples were exposed to HgCl{sub 2} or MeHg to derive IC50 values and inhibition constants (K {sub i}). Results demonstrate that HgCl{sub 2} is a more potent inhibitor of mACh receptor binding than MeHg, and the receptors in the cerebellum are more sensitive to Hg-mediated mACh receptor inhibition than those in the cerebral cortex. Species sensitivities, irrespective of Hg type and brain region, can be ranked from most to least sensitive: river otter > rat > mink > mouse > humans. In summary, our data demonstrate that Hg can inhibit the binding [{sup 3}H]-QNB to the mACh receptor in a range of mammalian species. This comparative study provides data on interspecies differences and a framework for interpreting results from human, murine, and wildlife studies.« less

Molecular analysis of nicotinic receptor expression in autism.

PubMed

Martin-Ruiz, C M; Lee, M; Perry, R H; Baumann, M; Court, J A; Perry, E K

2004-04-07

Autism is a developmental disorder of unknown aetiopathology and lacking any specific pharmacological therapeutic intervention. Neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA) and acetylcholine have been implicated. Abnormalities in nicotinic acetylcholine receptors have been identified including cortical loss of binding to the alpha4/beta2 subtype and increase in cerebellar alpha7 binding. Receptor expression (mRNA) has not so far been systematically examined. This study aims to further explore the role of nicotinic receptors in autism by analysing nicotinic receptor subunit mRNA in conjunction with protein levels and receptor binding in different brain areas. Quantitative RT-PCR for alpha4, alpha7 and beta2 subunit mRNA expression levels; alpha3, alpha4, alpha7 and beta2 subunit protein expression immunochemistry and specific radioligand receptor binding were performed in adult autism and control brain samples from cerebral cortex and cerebellum. Alpha4 and beta2 protein expression and receptor binding density as well as alpha4 mRNA levels were lower in parietal cortex in autism, while alpha7 did not change for any of these parameters. In cerebellum, alpha4 mRNA expression was increased, whereas subunit protein and receptor levels were decreased. Alpha7 receptor binding in cerebellum was increased alongside non-significant elevations in mRNA and protein expression levels. No significant changes were found for beta2 in cerebellum. The data obtained, using complementary measures of receptor expression, indicate that reduced gene expression of the alpha4beta2 nicotinic receptor in the cerebral cortex is a major feature of the neurochemical pathology of autism, whilst post-transcriptional abnormalities of both this and the alpha7 subtype are apparent in the cerebellum. The findings point to dendritic and/or synaptic nicotinic receptor abnormalities that may relate to disruptions in cerebral circuitry development.

Microglia in the Cerebral Cortex in Autism

ERIC Educational Resources Information Center

Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

2012-01-01

We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer’s Disease of humans and mice

PubMed Central

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J.; Sullivan, Patrick M.; Morgan, Todd E.; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olaf; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E.

2015-01-01

The APOE4 allele confers greater risk of Alzheimer’s Disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment (MCI) and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in two clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes. At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy (CAA), plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and CAA increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds vs the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. PMID:26686669

Experimental and clinical study of EHF treatment of vascular-vestibular dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mal`tsev, A.E.; Abakarov, A.T.; Istomin, V.S.

1994-07-01

The authors present the results of a study of the effectiveness of EHF radiation on the cerebral hemodynamics, bioelectrical activity of the cerebral cortex, and functional state of the vestibular analyzer in chronic studies of cats using a model of vascular-vestibular dysfunction. The clinical part of the work reflects the results of studies of the functional state of cerebral blood circulation and the vestibular analyzer during the EHF treatment of angiovertebrogenic vestibular dysfunction in a background of initial manifestations of cerebral blood supply deficiency (angiodistonic variant).

Aging, self-referencing, and medial prefrontal cortex.

PubMed

Gutchess, Angela H; Kensinger, Elizabeth A; Schacter, Daniel L

2007-01-01

The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults.

A Synaptic Basis for Memory Storage in the Cerebral Cortex

NASA Astrophysics Data System (ADS)

Bear, Mark F.

1996-11-01

A cardinal feature of neurons in the cerebral cortex is stimulus selectivity, and experience-dependent shifts in selectivity are a common correlate of memory formation. We have used a theoretical ``learning rule,'' devised to account for experience-dependent shifts in neuronal selectivity, to guide experiments on the elementary mechanisms of synaptic plasticity in hippocampus and neocortex. These experiments reveal that many synapses in hippocampus and neocortex are bidirectionally modifiable, that the modifications persist long enough to contribute to long-term memory storage, and that key variables governing the sign of synaptic plasticity are the amount of NMDA receptor activation and the recent history of cortical activity.

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

Two-photon laser scanning microscopy imaging of intact spinal cord and cerebral cortex reveals requirement for CXCR6 and neuroinflammation in immune cell infiltration of cortical injury sites.

PubMed

Kim, Jiyun V; Jiang, Ning; Tadokoro, Carlos E; Liu, Liping; Ransohoff, Richard M; Lafaille, Juan J; Dustin, Michael L

2010-01-31

The mouse spinal cord is an important site for autoimmune and injury models. Skull thinning surgery provides a minimally invasive window for microscopy of the mouse cerebral cortex, but there are no parallel methods for the spinal cord. We introduce a novel, facile and inexpensive method for two-photon laser scanning microscopy of the intact spinal cord in the mouse by taking advantage of the naturally accessible intervertebral space. These are powerful methods when combined with gene-targeted mice in which endogenous immune cells are labeled with green fluorescent protein (GFP). We first demonstrate that generation of the intervertebral window does not elicit a reaction of GFP(+) microglial cells in CX3CR1(gfp/+) mice. We next demonstrate a distinct rostrocaudal migration of GFP(+) immune cells in the spinal cord of CXCR6(gfp/+) mice during active experimental autoimmune encephalomyelitis (EAE). Interestingly, infiltration of the cerebral cortex by GFP(+) cells in these mice required three conditions: EAE induction, cortical injury and expression of CXCR6 on immune cells. Copyright 2009 Elsevier B.V. All rights reserved.

Differential expression of glutamate transporters EAAT1 and EAAT2 in mice deficient for PACAP-type I receptor.

PubMed

Zink, M; Schmitt, A; Henn, F A; Gass, P

2004-12-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates glutamatergic neurotransmission and induces the expression of glutamate transporters EAAT1 and EAAT2 in newborn mouse astroglial cell cultures. Since nanomolar concentrations of PACAP exert this effect, signal transduction via the high affinity PACAP-type I-receptor PAC1 was assumed. To test this hypothesis and to assess the importance of PAC1-signalling in vivo, we analyzed glutamate transporter expression in mice with a PAC1 knockout. EAAT1 and EAAT2 expression was investigated in the hippocampus and the cerebral cortex of PAC1 mutant mice and wildtype littermates by semiquantitative in-situ-hybridization. PAC1-knockout mice show a subtle but significant reduction of EAAT1 expression in the dentate gyrus. In contrast, reduced expression levels of EAAT1 in the cerebral cortex did not reach statistical significance and EAAT2 expression was unchanged in CA3 and cerebral cortex of PAC1 mutant mice. Our data confirm the previously reported in-vitro-regulation of EAAT1 in the adult nervous system in vivo. EAAT2 expression, however, is unchanged in PAC1 knockout mice, most likely due to counterbalancing factors.

Role of cerebellum in learning postural tasks.

PubMed

Ioffe, M E; Chernikova, L A; Ustinova, K I

2007-01-01

For a long time, the cerebellum has been known to be a structure related to posture and equilibrium control. According to the anatomic structure of inputs and internal structure of the cerebellum, its role in learning was theoretically reasoned and experimentally proved. The hypothesis of an inverse internal model based on feedback-error learning mechanism combines feedforward control by the cerebellum and feedback control by the cerebral motor cortex. The cerebellar cortex is suggested to acquire internal models of the body and objects in the external world. During learning of a new tool the motor cortex receives feedback from the realized movement while the cerebellum produces only feedforward command. To realize a desired movement without feedback of the realized movement, the cerebellum needs to form an inverse model of the hand/arm system. This suggestion was supported by FMRi data. The role of cerebellum in learning new postural tasks mainly concerns reorganization of natural synergies. A learned postural pattern in dogs has been shown to be disturbed after lesions of the cerebral motor cortex or cerebellar nuclei. In humans, learning voluntary control of center of pressure position is greatly disturbed after cerebellar lesions. However, motor cortex and basal ganglia are also involved in the feedback learning postural tasks.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

Cellular consequences of sleep deprivation in the brain.

PubMed

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Perception of Upright: Multisensory Convergence and the Role of Temporo-Parietal Cortex

PubMed Central

Kheradmand, Amir; Winnick, Ariel

2017-01-01

We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such “orientation constancy” is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i) neurobehavioral aspects of orientation constancy, (ii) sensory models that address the neurophysiology underlying perception of upright, and (iii) the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function. PMID:29118736

Cerebral blood flow modulation by Basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes.

PubMed

Takata, Norio; Nagai, Terumi; Ozawa, Katsuya; Oe, Yuki; Mikoshiba, Katsuhiko; Hirase, Hajime

2013-01-01

We report that a brief electrical stimulation of the nucleus basalis of Meynert (NBM), the primary source of cholinergic projection to the cerebral cortex, induces a biphasic cerebral cortical blood flow (CBF) response in the somatosensory cortex of C57BL/6J mice. This CBF response, measured by laser Doppler flowmetry, was attenuated by the muscarinic type acetylcholine receptor antagonist atropine, suggesting a possible involvement of astrocytes in this type of CBF modulation. However, we find that IP3R2 knockout mice, which lack cytosolic Ca2+ surges in astrocytes, show similar CBF changes. Moreover, whisker stimulation resulted in similar degrees of CBF increase in IP3R2 knockout mice and the background strain C57BL/6J. Our results show that neural activity-driven CBF modulation could occur without large cytosolic increases of Ca2+ in astrocytes.

Characterization of Atrophic Changes in the Cerebral Cortex Using Fractal Dimensional Analysis

PubMed Central

George, Anuh T.; Jeon, Tina; Hynan, Linda S.; Youn, Teddy S.; Kennedy, David N.; Dickerson, Bradford

2010-01-01

The purpose of this project is to apply a modified fractal analysis technique to high-resolution T1 weighted magnetic resonance images in order to quantify the alterations in the shape of the cerebral cortex that occur in patients with Alzheimer’s disease. Images were selected from the Alzheimer’s Disease Neuroimaging Initiative database (Control N=15, Mild-Moderate AD N=15). The images were segmented using a semi-automated analysis program. Four coronal and three axial profiles of the cerebral cortical ribbon were created. The fractal dimensions (Df) of the cortical ribbons were then computed using a box-counting algorithm. The mean Df of the cortical ribbons from AD patients were lower than age-matched controls on six of seven profiles. The fractal measure has regional variability which reflects local differences in brain structure. Fractal dimension is complementary to volumetric measures and may assist in identifying disease state or disease progression. PMID:20740072

Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas.

PubMed

Palesi, Fulvia; De Rinaldis, Andrea; Castellazzi, Gloria; Calamante, Fernando; Muhlert, Nils; Chard, Declan; Tournier, J Donald; Magenes, Giovanni; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

2017-10-09

Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

Brain processing of rectal sensation in adolescents with functional defecation disorders and healthy controls.

PubMed

Mugie, S M; Koppen, I J N; van den Berg, M M; Groot, P F C; Reneman, L; de Ruiter, M B; Benninga, M A

2018-03-01

Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross-sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs). We included 15 adolescents with FC, 10 adolescents with FNRFI, and 15 young adult HCs. Rectal barostat was performed prior to functional magnetic resonance imaging (fMRI) to determine individual pressure thresholds for urge sensation. Subjects received 2 sessions of 5 × 30 seconds of barostat stimulation during the acquisition of blood oxygenation level-dependent fMRI. Functional magnetic resonance imaging signal differences were analyzed using SPM8 in Matlab. Functional constipation and FNRFI patients had higher thresholds for urgency than HCs (P < .001). During rectal distension, FC patients showed activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior parietal lobule, and putamen. No activations were observed in controls and FNRFI patients. Functional nonretentive fecal incontinence patients showed deactivation in the hippocampus, parahippocampal gyrus, fusiform gyrus (FFG), lingual gyrus, posterior parietal cortex, and precentral gyrus. In HCs, deactivated areas were detected in the hippocampus, amygdala, FFG, insula, thalamus, precuneus, and primary somatosensory cortex. In contrast, no regions with significant deactivation were detected in FC patients. Children with FC differ from children with FNRFI and HCs with respect to patterns of cerebral activation and deactivation during rectal distension. Functional nonretentive fecal incontinence patients seem to resemble HCs when it comes to brain processing of rectal distension. © 2017 John Wiley & Sons Ltd.

Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN)

PubMed Central

2018-01-01

Abstract The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes. PMID:29379878

EFFECT OF PREGNANCY ON AUTOREGULATION OF CEREBRAL BLOOD FLOW IN ANTERIOR VERSUS POSTERIOR CEREBRUM

PubMed Central

Cipolla, Marilyn J.; Bishop, Nicole; Chan, Siu-Lung

2012-01-01

Severe pre/eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly due to decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5–6/group) and endothelial and neuronal nitric oxide synthase expression using quantitative polymerase chain reaction (n=3/group). In nonpregnant animals, there was no difference in autoregulation between anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal nitric oxide synthase expression in the posterior cerebral cortex vs. anterior. Compared to the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial nitric oxide synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not due to changes in sympathetic innervation. These findings suggest that although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension. PMID:22824983

Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum.

PubMed

Cipolla, Marilyn J; Bishop, Nicole; Chan, Siu-Lung

2012-09-01

Severe preeclampsia and eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly because of decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague-Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5-6 per group) and endothelial and neuronal NO synthase expression using quantitative PCR (n=3 per group). In nonpregnant animals, there was no difference in autoregulation between the anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal NO synthase expression in the posterior cerebral cortex versus anterior. Compared with the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial NO synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not attributed to changes in sympathetic innervation. These findings suggest that, although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension.

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

PubMed Central

Hou, Yan; Ouyang, Xin; Wan, Ruiqian; Cheng, Heping; Mattson, Mark P.; Cheng, Aiwu

2012-01-01

Although high amounts of reactive oxygen species (ROS) can damage cells, ROS can also play roles as second messengers, regulating diverse cellular processes. Here we report that embryonic mouse cerebral cortical neural progenitor cells (NPCs) exhibit intermittent spontaneous bursts of mitochondrial superoxide (SO) generation (mitochondrial SO flashes) that require transient opening of membrane permeability transition pores (mPTP). This quantal SO production negatively regulates NPC self-renewal. Mitochondrial SO scavengers and mPTP inhibitors reduce SO flash frequency and enhance NPC proliferation, whereas prolonged mPTP opening and SO generation increase SO flash incidence and decrease NPC proliferation. The inhibition of NPC proliferation by mitochondrial SO involves suppression of extracellular signal-regulated kinases. Moreover, mice lacking SOD2 (SOD2−/− mice) exhibit significantly fewer proliferative NPCs and differentiated neurons in the embryonic cerebral cortex at mid-gestation compared with wild type littermates. Cultured SOD2−/− NPCs exhibit a significant increase in SO flash frequency and reduced NPC proliferation. Taken together, our findings suggest that mitochondrial SO flashes negatively regulate NPC self-renewal in the developing cerebral cortex. PMID:22949407

Quantifying the pattern of beta/A4 amyloid protein distribution in Alzheimer's disease by image analysis.

PubMed

Bruce, C V; Clinton, J; Gentleman, S M; Roberts, G W; Royston, M C

1992-04-01

We have undertaken a study of the distribution of the beta/A4 amyloid deposited in the cerebral cortex in Alzheimer's disease. Previous studies which have examined the differential distribution of amyloid in the cortex in order to determine the laminar pattern of cortical pathology have not proved to be conclusive. We have developed an alternative method for the solution of this problem. It involves the immunostaining of sections followed by computer-enhanced image analysis. A mathematical model is then used to describe both the amount and the pattern of amyloid across the cortex. This method is both accurate and reliable and also removes many of the problems concerning inter and intra-rater variability in measurement. This method will provide the basis for further quantitative studies on the differential distribution of amyloid in Alzheimer's disease and other cases of dementia where cerebral amyloidosis occurs.

Suppression of phase synchronisation in network based on cat's brain.

PubMed

Lameu, Ewandson L; Borges, Fernando S; Borges, Rafael R; Iarosz, Kelly C; Caldas, Iberê L; Batista, Antonio M; Viana, Ricardo L; Kurths, Jürgen

2016-04-01

We have studied the effects of perturbations on the cat's cerebral cortex. According to the literature, this cortex structure can be described by a clustered network. This way, we construct a clustered network with the same number of areas as in the cat matrix, where each area is described as a sub-network with a small-world property. We focus on the suppression of neuronal phase synchronisation considering different kinds of perturbations. Among the various controlling interventions, we choose three methods: delayed feedback control, external time-periodic driving, and activation of selected neurons. We simulate these interventions to provide a procedure to suppress undesired and pathological abnormal rhythms that can be associated with many forms of synchronisation. In our simulations, we have verified that the efficiency of synchronisation suppression by delayed feedback control is higher than external time-periodic driving and activation of selected neurons of the cat's cerebral cortex with the same coupling strengths.

Cerebral blood flow changes in very-late-onset schizophrenia-like psychosis with catatonia before and after successful treatment.

PubMed

Tsujino, Naohisa; Nemoto, Takahiro; Yamaguchi, Taiju; Katagiri, Naoyuki; Tohgi, Nao; Ikeda, Ryu; Shiraga, Nobuyuki; Mizumura, Sunao; Mizuno, Masafumi

2011-10-01

The purpose of the present study was to investigate regional cerebral blood flow (rCBF) changes in a patient with very-late-onset schizophrenia-like psychosis (VLOS) with catatonia. A 64-year-old woman developed catatonia after experiencing persecutory delusions. The patient's rCBF was examined using single photon emission computed tomography (SPECT) with easy Z-score imaging system. Before treatment, hypoperfusion was observed in the striatum and the thalamus, whereas hyperperfusion was observed in the left lateral frontal cortex and the left temporal cortex. After treatment, the disproportions in rCBF disappeared, and hyperperfusion was observed in the motor cortex. Sequential SPECT findings suggest that rCBF abnormalities may be correlated with the symptomatology of catatonia in patients with VLOS. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Natural speech reveals the semantic maps that tile human cerebral cortex

PubMed Central

Huth, Alexander G.; de Heer, Wendy A.; Griffiths, Thomas L.; Theunissen, Frédéric E.; Gallant, Jack L.

2016-01-01

The meaning of language is represented in regions of the cerebral cortex collectively known as the “semantic system”. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modeling of fMRI data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that appear consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods—commonplace in studies of human neuroanatomy and functional connectivity—provide a powerful and efficient means for mapping functional representations in the brain. PMID:27121839

Quantitative comparison of high-resolution MRI and myelin-stained histology of the human cerebral cortex.

PubMed

Osechinskiy, Sergey; Kruggel, Frithjof

2009-01-01

The architectonic analysis of the human cerebral cortex is presently based on the examination of stained tissue sections. Recent progress in high-resolution magnetic resonance imaging (MRI) promotes the feasibility of an in vivo architectonic analysis. Since the exact relationship between the laminar fine-structure of a cortical MRI signal and histological cyto-and myeloarchitectonic staining patterns is not known, a quantitative study comparing high-resolution MRI to histological ground truth images is necessary for validating a future MRI based architectonic analysis. This communication describes an ongoing study comparing post mortem MR images to a myelin-stained histology of the brain cortex. After establishing a close spatial correspondence between histological sections and MRI using a slice-to-volume nonrigid registration algorithm, transcortical intensity profiles, extracted from both imaging modalities along curved trajectories of a Laplacian vector field, are compared via a cross-correlational analysis.

[The antioxidant prevention of disorders in calcium ion metabolism under the action of glutamate on the synaptosomes of the rat cerebral cortex].

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tiurina, Iu Iu; Tiurin, V A

1999-04-01

An increase of intracellular calcium ion concentration and of the 45Ca2+ entry, a decrease in Na+,K(+)-ATPase activity, and activation of Na+/Ca2+ exchange were shown to be initiated by glutamate in the rat brain cortex synaptosomes. These effects could be prevented with antagonists and blocking agents of the NMDA receptors. Pre-incubation of the synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 was shown to normalise [45Ca2+], the rate of 45Ca2+ entry, and the activity of Na+,K(+)-ATPase in the synaptosomes. The data obtained suggest that calcium ions entering the brain cortex neurones via the NMDA receptors in presence of excessive glutamate, trigger activation of free radical reactions damaging the neurones in ischemia, cerebral lesions, and other pathological conditions.

Relations of Blood Pressure and Head Injury to Regional Cerebral Blood Flow

PubMed Central

Allen, Allyssa J.; Katzel, Leslie I.; Wendell, Carrington R.; Siegel, Eliot L.; Lefkowitz, David; Waldstein, Shari R.

2016-01-01

Hypertension confers increased risk for cognitive decline, dementia, and cerebrovascular disease. These associations have been attributed, in part, to cerebral hypoperfusion. Here we posit that relations of higher blood pressure to lower levels of cerebral perfusion may be potentiated by a prior head injury. Participants were 87 community-dwelling older adults -69% men, 90% white, mean age= 66.9 years, 27.6% with a history of mild traumatic brain injury (mTBI) defined as a loss of consciousness

Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms.

PubMed

Shin, Hwa Kyoung; Salomone, Salvatore; Potts, E Michelle; Lee, Sae-Won; Millican, Eric; Noma, Kensuke; Huang, Paul L; Boas, David A; Liao, James K; Moskowitz, Michael A; Ayata, Cenk

2007-05-01

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.

Cryptotanshinone exhibits therapeutical effects on cerebral stroke through the PI3K/AKT‑eNOS signaling pathway.

PubMed

Zhu, Weixin; Qiu, Weihong; Lu, Ailan

2017-12-01

Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.

Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

PubMed Central

Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

2013-01-01

Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

The direct pathway from the brainstem reticular formation to the cerebral cortex in the ascending reticular activating system: A diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2015-10-08

Precise evaluation of the ascending reticular activating system (ARAS) is important for diagnosis, prediction of prognosis, and management of patients with disorders of impaired consciousness. In the current study, we attempted to reconstruct the direct neural pathway between the brainstem reticular formation (RF) and the cerebral cortex in normal subjects, using diffusion tensor imaging (DTI). Forty-one healthy subjects were recruited for this study. DTIs were performed using a sensitivity-encoding head coil at 1.5Tesla with FMRIB Software Library. For connectivity of the brainstem RF, we used two regions of interest (ROIs) for the brainstem RF (seed ROI) and the thalamus and hypothalamus (exclusion ROI). Connectivity was defined as the incidence of connection between the brainstem RF and target brain regions at the threshold of 5 and 50 streamlines. Regarding the thresholds of 5 and 50, the brainstem RF showed high connectivity to the lateral prefrontal cortex (lPFC, 67.1% and 20.7%) and ventromedial prefrontal cortex (vmPFC, 50.0% and 18.3%), respectively. In contrast, the brainstem RF showed low connectivity to the primary motor cortex (31.7% and 3.7%), premotor cortex (24.4% and 3.7%), primary somatosensory cortex (23.2% and 2.4%), orbitofrontal cortex (17.1% and 7.3%), and posterior parietal cortex (12.2% and 0%), respectively. The brainstem RF was mainly connected to the prefrontal cortex, particularly lPFC and vmPFC. We believe that the methodology and results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Functional Neuroanatomy for Posture and Gait Control

PubMed Central

Takakusaki, Kaoru

2017-01-01

Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling. PMID:28122432

[Effect of Reading a Book on a Tablet Computer on Cerebral Blood Flow in the Prefrontal Cortex].

PubMed

Sugiura, Akihiro; Eto, Takuya; Kinoshita, Fumiya; Takada, Hiroki

2018-01-01

By measuring cerebral blood flow in the prefrontal cortex, we aimed to determine how reading a book on a tablet computer affects sleep. Seven students (7 men age range, 21-32 years) participated in this study. In a controlled illuminance environment, the subjects read a novel in printed form or on a tablet computer from any distance. As the subjects were reading, the cerebral blood flow in their prefrontal cortex was measured by near-infrared spectroscopy. The study protocol was as follows. 1) Subjects mentally counted a sequence of numbers for 30 s as a pretest to standardized thinking and then 2) read the novel for 10 min, using the printed book or tablet computer. In step 2), the use of the book or tablet computer was in a random sequence. Subjects rested between the two tasks. Significantly increased brain activity (increase in regional cerebral blood flow) was observed following reading a novel on a tablet computer compared with that after reading a printed book. Furthermore, the region around Broca's area was more active when reading on a tablet computer than when reading a printed book. Considering the results of this study and previous studies on physiological characteristics during nonrapid eye movement sleep, we concluded that reading a book on a tablet computer before the onset of sleep leads to the potential inhibition of sound sleep through mechanisms other than the suppression of melatonin secretion.

Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model.

PubMed

Robertson, Nicola J; Kato, Takenori; Bainbridge, Alan; Chandrasekaran, Manigandan; Iwata, Osuke; Kapetanakis, Andrew; Faulkner, Stuart; Cheong, Jeanie; Iwata, Sachiko; Hristova, Mariya; Cady, Ernest; Raivich, Gennadij

2013-03-01

Na⁺/H⁺ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (³¹P) and proton (¹H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model. © 2012 International Society for Neurochemistry.

Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†

PubMed Central

Deng, Jiao; Zhang, Junfeng; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

2014-01-01

Aims About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia. Methods and results Six-week-old male CD1, C57BL/6J, and MMP-9−/− mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood–brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9−/− mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice. Conclusion HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects. PMID:24935427

Spatial embedding of structural similarity in the cerebral cortex

PubMed Central

Song, H. Francis; Kennedy, Henry; Wang, Xiao-Jing

2014-01-01

Recent anatomical tracing studies have yielded substantial amounts of data on the areal connectivity underlying distributed processing in cortex, yet the fundamental principles that govern the large-scale organization of cortex remain unknown. Here we show that functional similarity between areas as defined by the pattern of shared inputs or outputs is a key to understanding the areal network of cortex. In particular, we report a systematic relation in the monkey, human, and mouse cortex between the occurrence of connections from one area to another and their similarity distance. This characteristic relation is rooted in the wiring distance dependence of connections in the brain. We introduce a weighted, spatially embedded random network model that robustly gives rise to this structure, as well as many other spatial and topological properties observed in cortex. These include features that were not accounted for in any previous model, such as the wide range of interareal connection weights. Connections in the model emerge from an underlying distribution of spatially embedded axons, thereby integrating the two scales of cortical connectivity—individual axons and interareal pathways—into a common geometric framework. These results provide insights into the origin of large-scale connectivity in cortex and have important implications for theories of cortical organization. PMID:25368200

Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex.

PubMed

Romanova, G A; Mirzoev, T K; Barskov, I V; Victorov, I V; Gudasheva, T A; Ostrovskaya, R U

2000-09-01

Antiamnestic effect of acyl-prolyl-containing dipeptide GVS-111 was demonstrated in rats with bilateral compression-induced damage to the frontal cortex. Both intraperitoneal and oral administration of the dipeptide improved retrieval of passive avoidance responses in rats with compression-induced cerebral ischemia compared to untreated controls.

Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes.

PubMed Central

Guard, S.; Watson, S. P.; Maggio, J. E.; Too, H. P.; Watling, K. J.

1990-01-01

1. The binding properties and pharmacological specificity of the selective NK3 tachykinin receptor agonist [3H))-senktide [( 3H]-succinyl[Asp6,MePhe8] substance P (6-11] have been examined in homogenates of guinea-pig ileum longitudinal muscle-myenteric plexus (LM/MP) and cerebral cortex. 2. Scatchard analysis of saturation binding studies in guinea-pig ileum LM/MP and cerebral cortex membranes indicated that [3H]-senktide bound to a single site with apparent high affinity, KD = 2.21 +/- 0.65 nM; Bmax = 13.49 +/- 0.04 fmol mg-1 protein in ileum and KD = 8.52 +/- 0.45 nM; Bmax = 76.3 +/- 1.6 fmol mg-1 protein in cortex (values are means +/- ranges; n = 2). 3. The pharmacological profile for tachykinins and analogues in displacing [3H]-senktide from ileum membranes was: [MePhe7] neurokinin B greater than neurokinin B (NKB) congruent to senktide greater than eledoisin greater than substance P (SP) greater than neurokinin A(NKA) greater than physalaemin greater than [Sar9,Met(O2)11]SP greater than [Nle10]NKA(4-10) = [Glp6,L-Pro9]-SP(6-11) greater than substance P methyl ester, consistent with [3H]-senktide binding to an NK3 subtype of tachykinin receptor. A similar rank order of affinity was obtained for these peptides in displacing [3H]-senktide from cortex membranes. 4. Several tachykinin receptor agonists were tested for their ability to displace [3H]-senktide from ileal and cortical NK3 binding sites and were found to be either weak displacers (pIC50 less than 5.00) or inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1694464

Changes in oxidative metabolism and memory and learning in an cerebral hypoperfusion model in rats.

PubMed

Castaño Guerrero, Y; González Fraguela, M E; Fernández Verdecia, I; Horruitiner Gutiérrez, I; Piedras Carpio, S

2013-01-01

Chronic hypoperfusion in rats produces memory and learning impairments due to permanent occlusion of commun carotid arteries (POCCA). Molecular mechanisms leading to behavioural disorders have been poorly studied. For this reason, the aim of the present study was to characterise oxidative metabolism disorders and their implications in memory and learning impairments. Superoxide dismutase (SOD) and catalase (CAT) activities were determined in cortex, hippocampus and striatum homogenates at 24 hours and at 22 days after the lesion. Haematoxylin-eosin staining and glial fibrillary acidic protein (GFAP) immunoreactivity were performed on coronal sections. Behavioural impairments were explored using the Morris water maze (MWM). Escape latencies were determined in all behavioural studies. The lesion induced a significant increase (P<.01) in CAT activity in the cortex at 24 hours, while SOD activity was significantly higher (P<.01) in the cortex and hippocampus at 22 days. An intense vacuolization was observed in the cortex and striatum as a result of the lesion. A neuronal loss in the striatum and hippocampus was observed. The glial reaction increased in the cortex and striatum. Visual alterations were observed in the lesion group with the lowest evolution time (P<.001). Escape latencies, corresponding to MWM schemes for long-term and short-term memory evaluation increased significantly (P<.05) in both groups of lesioned animals. It was concluded that changes in SOD and CAT activities indicate a possible implication of oxidative imbalance in the pathology associated with chronic cerebral hypoperfusion. In addition, the POCCA model in rats is useful for understanding mechanisms by which cerebral hypoperfusion produces memory and learning impairments. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

[A case of MM1+2 Creutzfeldt-Jakob disease with a longitudinal study of EEG and MRI].

PubMed

Katsube, Mizuho; Shiota, Yuri; Harada, Takayuki; Shibata, Hiroshi; Nagai, Atsushi

2013-11-01

We report a case of definite MM1 + 2 sporadic Creutzfeldt-Jakob disease (sCJD). A 66-year-old woman was admitted to our hospital with memory disturbance and disorientation for three months. On admission she presented a progressive cognitive insufficiency. Electroencephalography (EEG) revealed a frontal intermittent rhythmical delta activity (FIRDA) and the brain magnetic resonance imaging (MRI) showed high signal intensities in cerebral cortex on diffusion weighted images (DWI). After four months from the onset, she reached the akinetic mutism state followed by myoclonus. Follow up examination revealed that periodic synchronous discharge (PSD) was found in EEG, and DWI revealed enlargement of high signal intensity lesions in cerebral cortex. At seven months from the onset, PSD and high signal intensities of cortex became unclear with disappearance of myoclonus, and brain white matter lesions were evident on MRI. Serial studies of EEG and MRI revealed that PSD generalized from frontal lobe dominant pattern, while high signal intensity lesions of cortex diffusely increased on DWI. At ten months from the onset patient died. Pathological examination in brain showed moderate and diffuse neuronal cell loss and gliosis in cerebral cortex corresponding with DWI changes. The genotype at codon 129 of the prion protein (PrP) was homozygous methionine (MM) and the type of protease-resistant PrP (PrPres) was the mixed type of 1 and 2 in Western blot analysis. It has been rare to analyze the changes of EEG and MRI in the entire stage and to investigate pathological finding in the case of sCJD-MM1 + 2. A longitudinal examination of EEG and MRI is useful for early diagnosis of CJD. Also we could correlate these findings with clinical and histopathological phenotype.

Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

PubMed

Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

2017-01-01

Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1 H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P < 0.01) and [glutamate]/[glutamine] ratio (P < 0.05). Lower taurine concentrations were observed in the hippocampus (P < 0.01) and striatum (P < 0.05). IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.

PubMed

Kinze, S; Schöneberg, T; Meyer, R; Martin, H; Kaufmann, R

1996-10-11

In this paper, cholecystokinin (CCK) B-type binding sites were characterized with receptor binding studies in different human brain regions (various parts of cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellar cortex) collected from 22 human postmortem brains. With the exception of the thalamus, where no specific CCK binding sites were found, a pharmacological characterization demonstrated a single class of high affinity CCK sites in all brain areas investigated. Receptor densities ranged from 0.5 fmol/mg protein (hippocampus) to 8.4 fmol/mg protein (nucleus caudatus). These CCK binding sites displayed a typical CCKA binding profile as shown in competition studies by using different CCK-related compounds and non peptide CCK antagonists discriminating between CCKA and CCKB sites. The rank order of agonist or antagonist potency in inhibiting specific sulphated [propionyl-3H]cholecystokinin octapeptide binding was similar and highly correlated for the brain regions investigated as demonstrated by a computer-assisted analysis. Therefore it is concluded that CCKB binding sites in human cerebral cortex, basal ganglia, cerebellar cortex share identical ligand binding characteristics.

Increasing CNS norepinephrine levels by the precursor L-DOPS facilitates beam-walking recovery after sensorimotor cortex ablation in rats.

PubMed

Kikuchi, K; Nishino, K; Ohyu, H

2000-03-31

The present investigation was conducted to document a role of L-threo-3,4-dihydroxyphenylserine (L-DOPS), precursor of L-norepinephrine (NE), in the functional recovery from beam-walking performance deficits in rats after unilateral sensorimotor cortex ablation. L-DOPS was administered simultaneously with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor), and the regional contents of NE in the cerebral cortex, hippocampus, and cerebellum were assayed. Behavioral recovery was demonstrated by the rats treated with L-DOPS and BSZ, and the rate of recovery was significantly different from that of either BSZ-treated or vehicle-treated control rats. The NE tissue levels in the three discrete regions of the rat brain were significantly elevated in the experimental rats receiving both L-DOPS and BSZ. The present studies indicate that increasing NE levels by the precursor L-DOPS may be responsible for facilitating behavioral recovery from beam-walking performance deficits in rats, and further suggest that L-DOPS may become one of the candidate compounds for further clinical human trials promoting functional recovery after injuries to the cerebral cortex.

Progesterone receptor isoforms expression pattern in the rat brain during the estrous cycle.

PubMed

Guerra-Araiza, C; Cerbón, M A; Morimoto, S; Camacho-Arroyo, I

2000-03-24

Progesterone receptor (PR) isoforms expression was determined in the hypothalamus, the preoptic area, the hippocampus and the frontal cerebral cortex of the rat at 12:00 h on each day of the estrous cycle by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10 h light-dark cycle, with lights on at 06:00 h were used. We found that PR-B isoform was predominant in the hypothalamus, the preoptic area and the frontal cerebral cortex. Both PR isoforms were similarly expressed in the hippocampus. The highest PR-B expression was found on proestrus day in the hypothalamus; on metestrus in the preoptic area; and on diestrus in the frontal cortex. We observed no changes in PR isoforms expression in the hippocampus during the estrous cycle. These results indicate that PR isoforms expression is differentially regulated during the estrous cycle in distinct brain regions and that PR-B may be involved in progesterone actions upon the hypothalamus, the preoptic area and the frontal cortex of the rat.

Changes in canine cerebral perfusion after accelerated high frequency repetitive transcranial magnetic stimulation (HF-rTMS): A proof of concept study.

PubMed

Dockx, R; Baeken, C; Duprat, R; De Vos, F; Saunders, J H; Polis, I; Audenaert, K; Peremans, K

2018-04-01

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for several neuropsychiatric disorders in human beings, but the neurobiological effects of rTMS in dogs have not been investigated to date. A proof of concept study was designed to evaluate the effect of rTMS on cerebral perfusion, measured with single photon emission computed tomography (SPECT), in dogs. An accelerated high frequency (aHF)-rTMS (20Hz) protocol was applied to the canine left frontal cortex. To accurately target this area, eight dogs underwent a 3 Tesla magnetic resonance imaging (MRI) scan before stimulation. The left frontal cortex was subjected to five consecutive aHF-rTMS sessions with a figure-of-eight coil designed for human beings at an intensity of 110% of the motor threshold. The dogs underwent 99m Tc-d,1 hexamethylpropylene amine oxime (HMPAO) SPECT scans 1 week prior to and 1day after the stimulations. Perfusion indices (PIs) were determined semi-quantitatively; aHF-rTMS resulted in significantly increased PIs in the left frontal cortex and the subcortical region, whereas no significant differences were noted for the other regions. Behaviour was not influenced by the stimulation sessions. As has been observed in human beings, aHF-rTMS applied to the left frontal cortex alters regional cerebral perfusion in dogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations.

PubMed

Beinfeld, Margery C; Blum, Alissa; Vishnuvardhan, Daesety; Fanous, Sanya; Marchand, James E

2005-11-18

Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain. To examine its role in cholecystokinin processing, cholecystokinin levels were measured in dissected brain regions from prohormone convertase 2 knock-out mice. Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice. In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type. Female mice were more affected by the loss of prohormone convertase 2 than male mice. The decrease in cholecystokinin levels in these brain regions shows that prohormone convertase 2 is important for cholecystokinin processing. Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression. They revealed that cholecystokinin and prohormone convertase 1 mRNA levels in cerebral cortex and olfactory bulb were actually lower in knock-out than wild type, whereas their expression in other brain regions of knock-out mouse brain was the same as wild type. Female mice frequently had higher expression of cholecystokinin and prohormone convertase 1, 2, and 5 mRNA than male mice. The loss of prohormone convertase 2 alters CCK processing in specific brain regions. This loss also appears to trigger compensatory mechanisms in cerebral cortex and olfactory bulb that produce elevated levels of cholecystokinin but do not involve increased expression of cholecystokinin, prohormone convertase 1 or 5 mRNA.

Excessive daytime sleepiness in Parkinson disease: a SPECT study.

PubMed

Matsui, Hideaki; Nishinaka, Kazuto; Oda, Masaya; Hara, Narihiro; Komatsu, Kenichi; Kubori, Tamotsu; Udaka, Fukashi

2006-07-01

The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. Clinical study. Sumitomo Hospital. Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Prefrontal Hemodynamics in Toddlers at Rest: A Pilot Study of Developmental Variability

PubMed Central

Anderson, Afrouz A.; Smith, Elizabeth; Chowdhry, Fatima A.; Thurm, Audrey; Condy, Emma; Swineford, Lauren; Manwaring, Stacy S.; Amyot, Franck; Matthews, Dennis; Gandjbakhche, Amir H.

2017-01-01

Functional near infrared spectroscopy (fNIRS) is a non-invasive functional neuroimaging modality. Although, it is amenable to use in infants and young children, there is a lack of fNIRS research within the toddler age range. In this study, we used fNIRS to measure cerebral hemodynamics in the prefrontal cortex (PFC) in 18–36 months old toddlers (n = 29) as part of a longitudinal study that enrolled typically-developing toddlers as well as those “at risk” for language and other delays based on presence of early language delays. In these toddlers, we explored two hemodynamic response indices during periods of rest during which time audiovisual children's programming was presented. First, we investigate Lateralization Index, based on differences in oxy-hemoglobin saturation from left and right prefrontal cortex. Then, we measure oxygenation variability (OV) index, based on variability in oxygen saturation at frequencies attributed to cerebral autoregulation. Preliminary findings show that lower cognitive (including language) abilities are associated with fNIRS measures of both lower OV index and more extreme Lateralization index values. These preliminary findings show the feasibility of using fNIRS in toddlers, including those at risk for developmental delay, and lay the groundwork for future studies. PMID:28611578

The protocadherin 11X/Y (PCDH11X/Y) gene pair as determinant of cerebral asymmetry in modern Homo sapiens.

PubMed

Priddle, Thomas H; Crow, Timothy J

2013-06-01

Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single "right-shift" gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X-Y homologous region of the sex chromosomes. The Xq21.3/Yp11.2 human-specific region of homology includes the protocadherin 11X/Y (PCDH11X/Y) gene pair, which encode cell adhesion molecules subject to accelerated evolution following the separation of the human and chimpanzee lineages six million years ago. PCDH11X and PCDH11Y, differentially regulated by retinoic acid, are highly expressed in the ventricular zone, subplate, and cortical plate of the developing cerebral cortex. Both proteins interact with β-catenin, a protein that plays a role in determining axis formation and regulating cortical size. In this way, the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens. © 2013 New York Academy of Sciences.

Bereitschaftspotential as an indicator of movement preparation in supplementary motor area and motor cortex.

PubMed

Deecke, L

1987-01-01

Topographical studies in humans of the Bereitschaftspotential (BP, or readiness potential, as averaged from the electroencephalogram) and the Bereitschaftsmagnetfeld (BM, or readiness magnetic field, as averaged from the magnetoencephalogram) revealed a widespread distribution of motor preparation over both hemispheres even before unilateral movement. This indicates the existence of several generators responsible for the BP, including generators in the ipsilateral hemisphere, which is in agreement with measurements of regional cerebral blood flow or regional cerebral energy metabolism. Nevertheless, two principal generators seem to prevail: (1) An early generator, starting its activity 1s or more before the motor act, with its maximum at the vertex. For this and other reasons, early BP generation probably stems from cortical tissue representing or including the supplementary motor area (SMA). (2) A later generator, starting its activity about 0.5s before the onset of movement and biased towards the contralateral hemisphere (contralateral preponderance of negativity, CPN). For unilateral finger movements the CPN succeeds the BP's initial bilateral symmetry in the later preparation period. Thus, this lateralized BP component probably stems from the primary motor area, MI (area 4, hand representation). While regional cerebral blood flow or regional cerebral energy metabolism show that the SMA is active in conjunction with motor acts, these data do not permit the conclusion that SMA activity precedes motor acts. This can only be shown by the Bereitschaftspotential, which proves that SMA activity occurs before the onset of movement and, what is more, before the onset of MI activity. This important order of events (first SMA, then MI activation) has been elucidated by our BP studies. It gives the SMA an important functional role: the initiation of voluntary movement. The recording of movement-related potentials associated with manual hand-tracking and motor learning points to the SMA and frontal cortex having an important role in these functions.

Manipulating neuronal activity with low frequency transcranial ultrasound

NASA Astrophysics Data System (ADS)

Moore, Michele Elizabeth

Stimulation of the rodent cerebral cortex is used to investigate the underlying biological basis for the restorative effects of slow wave sleep. Neuronal activation by optogenetic and ultrasound stimulation elicits changes in action potentials across the cerebral cortex that are recorded as electroencephalograms. Optogenetic stimulation requires an invasive implantation procedure limiting its application in human studies. We sought to determine whether ultrasound stimulation could be as effective as optogenetic techniques currently used, in an effort to further understand the physiological and metabolic requirements of sleep. We successfully recorded electroencephalograms in response to transcranial ultrasound stimulation of the barrel cortex at 1 and 7 Hz frequencies, comparing them to those recorded in response to optogenetic stimuli applied at the same frequencies. Our results showed application of a 473 nm blue LED positioned 6 cm above the skull and ultrasound stimulation at an output voltage of 1000 mVpp produced electroencephalograms with physiological responses of similar amplitude. We concluded that there exists an intensity-proportionate response in the optogenetic stimulation, but not with ultrasound stimulation at the frequencies we surveyed. Activation of neuronal cells in response to optogenetic stimulation in a Thy1-ChR2 transgenic mouse line is specifically targeted to pyramidal cells in the cerebral cortex. ChR2 responses to optogenetic stimulation are mediated by a focal activation of neuronal ion channels. We measured electrophysiological responses to ultrasound stimulation, comparing them to those recorded from optogenetic stimuli. Our results show striking similarities between ultrasound-induced responses and optogenetically-induced responses, which may indicate that transcranial ultrasound stimulation is also mediated by ion channel dependent processes in cerebral cortical neurons. The biophysical substrates for electrical excitability of neurons impose temporal constraints on their response to stimulation. If ultrasound-mediated responses are, in fact, ion channel mediated responses, ultrasound-induced responses should exhibit time-dependence characteristics similar to those of optogenetically-triggered responses. Minimal stimulus duration thresholds and the temporal limits of paired pulse facilitation for ultrasound stimulation were identical to those of optogenetic stimulation. Collectively, these experiments demonstrate an electrophysiological basis for low-frequency transcranial ultrasound stimulation of cerebral cortical neuronal activity.

The use of in vivo fluorescence image sequences to indicate the occurrence and propagation of transient focal depolarizations in cerebral ischemia.

PubMed

Strong, A J; Harland, S P; Meldrum, B S; Whittington, D J

1996-05-01

A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.

Transcranial direct current stimulation combined with upper limb functional training in children with spastic, hemiparetic cerebral palsy: study protocol for a randomized controlled trial.

PubMed

Moura, Renata Calhes Franco; Santos, Cibele Almeida; Grecco, Luanda André Collange; Lazzari, Roberta Delasta; Dumont, Arislander Jonathan Lopes; Duarte, Natalia Carvalho de Almeida; Braun, Luiz Alfredo; Lopes, Jamile Benite Palma; Santos, Ligia Abram Dos; Rodrigues, Eliane Lopes Souza; Albertini, Giorgio; Cimolin, Veronica; Galli, Manuela; Oliveira, Claudia Santos

2016-08-17

The aim of the proposed study is to perform a comparative analysis of functional training effects for the paretic upper limb with and without transcranial direct current stimulation over the primary motor cortex in children with spastic hemiparetic cerebral palsy. The sample will comprise 34 individuals with spastic hemiparetic cerebral palsy, 6 to 16 years old, classified at level I, II, or III of the Manual Ability Classification System. Participants will be randomly allocated to two groups: (1) functional training of the paretic upper limb combined with anodic transcranial stimulation; (2) functional training of the paretic upper limb combined with sham transcranial stimulation. Evaluation will involve three-dimensional movement analysis and electromyography using the SMART-D 140® system (BTS Engineering) and the FREEEMG® system (BTS Engineering), the Quality of Upper Extremity Skills Test, to assess functional mobility, the Portable Device and Ashworth Scale, to measure movement resistance and spasticity, and the Pediatric Evaluation of Disability Inventory, to evaluate performance. Functional reach training of the paretic upper limb will include a range of manual activities using educational toys associated with an induced constraint of the non-paretic limb during the training. Training will be performed in five weekly 20-minute sessions for two weeks. Transcranial stimulation over the primary motor cortex will be performed during the training sessions at an intensity of 1 mA. Findings will be analyzed statistically considering a 5 % significance level (P ≤ 0.05). This paper presents a detailed description of a prospective, randomized, controlled, double-blind, clinical trial designed to demonstrate the effects of combining transcranial direct current stimulation over the primary motor cortex and functional training of the paretic limb in children with cerebral palsy classified at level I, II, or III of the Manual Ability Classification System. The results will be published and evidence found may contribute to the use of transcranial stimulation for this population. ReBEC RBR-6V4Y3K . Registered on 11 February 2015.

Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction.

PubMed

Yano, Kazuo; Kawasaki, Koh; Hattori, Tsuyoshi; Tawara, Shunsuke; Toshima, Yoshinori; Ikegaki, Ichiro; Sasaki, Yasuo; Satoh, Shin-ichi; Asano, Toshio; Seto, Minoru

2008-10-10

Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

PubMed Central

de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

2015-01-01

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

PubMed

McCarthy, Deirdre M; Bhide, Pradeep G

2012-01-01

Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

Electrical Cerebral Stimulation Modifies Inhibitory Systems

NASA Astrophysics Data System (ADS)

Cuéllar-Herrera, M.; Rocha, L.

2003-09-01

Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

Computer Modeling of Acceleration Effects on Cerebral Oxygen Saturation

DTIC Science & Technology

2007-04-01

a significant physiological threat to etrate the cranium and enter the cerebral cortex. Hongo high-performance aircraft pilots since the development...et al. and Hongo et al. (7,8). blackened out and all that could be seen was the target, The primary focus of this effort was to build a model i.e...O6GInduced.html. 87:402. 12. Tripp LD, Arnold A, Bagian J, et al. Psychophysiological effects 8. Hongo K, Kobayashi S, Okudera H, et al. Noninvasive cerebral of

Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex

PubMed Central

Thomson, Rachel E; Kind, Peter C; Graham, Nicholas A; Etherson, Michelle L; Kennedy, John; Fernandes, Ana C; Marques, Catia S; Hevner, Robert F; Iwata, Tomoko

2009-01-01

Background Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown. Results In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis. Conclusion Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex. PMID:19192266

An ovine model of cerebral catheter venography for implantation of an endovascular neural interface.

PubMed

Oxley, Thomas James; Opie, Nicholas Lachlan; Rind, Gil Simon; Liyanage, Kishan; John, Sam Emmanuel; Ronayne, Stephen; McDonald, Alan James; Dornom, Anthony; Lovell, Timothy John Haynes; Mitchell, Peter John; Bennett, Iwan; Bauquier, Sebastien; Warne, Leon Norris; Steward, Chris; Grayden, David Bruce; Desmond, Patricia; Davis, Stephen M; O'Brien, Terence John; May, Clive N

2018-04-01

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Embedding Task-Based Neural Models into a Connectome-Based Model of the Cerebral Cortex.

PubMed

Ulloa, Antonio; Horwitz, Barry

2016-01-01

A number of recent efforts have used large-scale, biologically realistic, neural models to help understand the neural basis for the patterns of activity observed in both resting state and task-related functional neural imaging data. An example of the former is The Virtual Brain (TVB) software platform, which allows one to apply large-scale neural modeling in a whole brain framework. TVB provides a set of structural connectomes of the human cerebral cortex, a collection of neural processing units for each connectome node, and various forward models that can convert simulated neural activity into a variety of functional brain imaging signals. In this paper, we demonstrate how to embed a previously or newly constructed task-based large-scale neural model into the TVB platform. We tested our method on a previously constructed large-scale neural model (LSNM) of visual object processing that consisted of interconnected neural populations that represent, primary and secondary visual, inferotemporal, and prefrontal cortex. Some neural elements in the original model were "non-task-specific" (NS) neurons that served as noise generators to "task-specific" neurons that processed shapes during a delayed match-to-sample (DMS) task. We replaced the NS neurons with an anatomical TVB connectome model of the cerebral cortex comprising 998 regions of interest interconnected by white matter fiber tract weights. We embedded our LSNM of visual object processing into corresponding nodes within the TVB connectome. Reciprocal connections between TVB nodes and our task-based modules were included in this framework. We ran visual object processing simulations and showed that the TVB simulator successfully replaced the noise generation originally provided by NS neurons; i.e., the DMS tasks performed with the hybrid LSNM/TVB simulator generated equivalent neural and fMRI activity to that of the original task-based models. Additionally, we found partial agreement between the functional connectivities using the hybrid LSNM/TVB model and the original LSNM. Our framework thus presents a way to embed task-based neural models into the TVB platform, enabling a better comparison between empirical and computational data, which in turn can lead to a better understanding of how interacting neural populations give rise to human cognitive behaviors.

Developmental Markers Expressed in Neocortical Layers Are Differentially Exhibited in Olfactory Cortex

PubMed Central

Brunjes, Peter C.; Osterberg, Stephen K.

2015-01-01

Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle) expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas. For example, while the AONpP, APC and PPC all broadly expressed the deep cortical marker CTIP2, NOR1 (NR4a3) levels were higher in AONpP and DAARP-32 was more prevalent in the APC and PPC. Similar findings were encountered for superficial cortical markers: all three regions broadly expressed CUX1, but CART was only observed in the APC and PPC. Furthermore, regional variations were observed even within single structures (e.g., NOR1 was found primarily in in the dorsal region of AONpP and CART expression was observed in a discrete band in the middle of layer 2 of both the APC and PPC). Experiments using the mitotic marker EDU verified that the olfactory cortices and neocortex share similar patterns of neuronal production: olfactory cells that express markers found in the deep neocortex are produced earlier than those that express superficial makers. Projection neurons were filled by retrograde tracers injected into the olfactory bulb to see if olfactory neurons with deep and superficial markers had different axonal targets. Unlike the cerebral cortex, no specificity was observed: neurons with each of the transcription factors examined were found to be labelled. Together the results indicate that olfactory cortices are complex: they differ from each other and each is formed from a variable mosaic of neurons. The results suggest that the olfactory cortices are not merely a remnant architype of the primordial forebrain but varied and independent regions. PMID:26407299

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System

PubMed Central

Steininger, Stefanie C.; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M.; Prüssmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. Methods: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Results: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Conclusion: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD. PMID:24672483

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

PubMed

Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

2014-01-01

Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

Temporal processing asymmetries between the cerebral hemispheres: evidence and implications.

PubMed

Nicholls, M E

1996-07-01

This paper reviews a large body of research which has investigated the capacities of the cerebral hemispheres to process temporal information. This research includes clinical, non-clinical, and electrophysiological experimentation. On the whole, the research supports the notion of a left hemisphere advantage for temporal resolution. The existence of such an asymmetry demonstrates that cerebral lateralisation is not limited to the higher-order functions such as language. The capacity for the resolution of fine temporal events appears to play an important role in other left hemisphere functions which require a rapid sequential processor. The functions that are facilitated by such a processor include verbal, textual, and fine movement skills. The co-development of these functions with an efficient temporal processor can be accounted for with reference to a number of evolutionary scenarios. Physiological evidence favours a temporal processing mechanism located within the left temporal cortex. The function of this mechanism may be described in terms of intermittency or travelling moment models of temporal processing. The travelling moment model provides the most plausible account of the asymmetry.

Combined magnitude and phase-based segmentation of the cerebral cortex in 7T MR images of the elderly.

PubMed

Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; Webb, Andrew G; van der Grond, Jeroen; van Buchem, Mark A; Reiber, Johan H C; Milles, Julien

2012-07-01

To propose a new method that integrates both magnitude and phase information obtained from magnetic resonance (MR) T*(2) -weighted scans for cerebral cortex segmentation of the elderly. This method makes use of K-means clustering on magnitude and phase images to compute an initial segmentation, which is further refined by means of transformation with reconstruction criteria. The method was evaluated against the manual segmentation of 7T in vivo MR data of 20 elderly subjects (age = 67.7 ± 10.9). The added value of combining magnitude and phase was also evaluated by comparing the performance of the proposed method with the results obtained when limiting the available data to either magnitude or phase. The proposed method shows good overlap agreement, as quantified by the Dice Index (0.79 ± 0.04), limited bias (average relative volume difference = 2.94%), and reasonable volumetric correlation (R = 0.555, p = 0.011). Using the combined magnitude and phase information significantly improves the segmentation accuracy compared with using either magnitude or phase. This study suggests that the proposed method is an accurate and robust approach for cerebral cortex segmentation in datasets presenting low gray/white matter contrast. Copyright © 2012 Wiley Periodicals, Inc.

Spatial eigenmodes and synchronous oscillation: co-incidence detection in simulated cerebral cortex.

PubMed

Chapman, Clare L; Wright, James J; Bourke, Paul D

2002-07-01

Zero-lag synchronisation arises between points on the cerebral cortex receiving concurrent independent inputs; an observation generally ascribed to nonlinear mechanisms. Using simulations of cerebral cortex and Principal Component Analysis (PCA) we show patterns of zero-lag synchronisation (associated with empirically realistic spectral content) can arise from both linear and nonlinear mechanisms. For low levels of activation, we show the synchronous field is described by the eigenmodes of the resultant damped wave activity. The first and second spatial eigenmodes (which capture most of the signal variance) arise from the even and odd components of the independent input signals. The pattern of zero-lag synchronisation can be accounted for by the relative dominance of the first mode over the second, in the near-field of the inputs. The simulated cortical surface can act as a few millisecond response coincidence detector for concurrent, but uncorrelated, inputs. As cortical activation levels are increased, local damped oscillations in the gamma band undergo a transition to highly nonlinear undamped activity with 40 Hz dominant frequency. This is associated with "locking" between active sites and spatially segregated phase patterns. The damped wave synchronisation and the locked nonlinear oscillations may combine to permit fast representation of multiple patterns of activity within the same field of neurons.

The Bat as a New Model of Cortical Development.

PubMed

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Ariza, Jeanelle; Rogers, Hailee; Horton-Sparks, Kayla; Kreutz, Anna; Behringer, Richard; Rasweiler, John J; Noctor, Stephen C

2017-11-09

The organization of the mammalian cerebral cortex shares fundamental features across species. However, while the radial thickness of grey matter varies within one order of magnitude, the tangential spread of the cortical sheet varies by orders of magnitude across species. A broader sample of model species may provide additional clues for understanding mechanisms that drive cortical expansion. Here, we introduce the bat Carollia perspicillata as a new model species. The brain of C. perspicillata is similar in size to that of mouse but has a cortical neurogenic period at least 5 times longer than mouse, and nearly as long as that of the rhesus macaque, whose brain is 100 times larger. We describe the development of laminar and regional structures, neural precursor cell identity and distribution, immune cell distribution, and a novel population of Tbr2+ cells in the caudal ganglionic eminence of the developing neocortex of C. perspicillata. Our data indicate that unique mechanisms guide bat cortical development, particularly concerning cell cycle length. The bat model provides new perspective on the evolution of developmental programs that regulate neurogenesis in mammalian cerebral cortex, and offers insight into mechanisms that contribute to tangential expansion and gyri formation in the cerebral cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A comparison of the effects of substance P and shorter analogues on the synaptosomal ATPases activities in the rat brain.

PubMed

Lachowicz, L; Janiszewska, G

1987-01-01

The influence in vitro of SP and C-terminal fragments of analogues SP(5-11) (pyroGlu5, Tyr8); SP(6-11) (pyroGlu6, Tyr8); SP(6-11) (pyroGlu6, D-Phe7); SP(6-11) (pyroGlu6, D-Phe8) on the (Ca, Mg) and (Na, K) ATPases activities from synaptosomal membranes of cerebral cortex and hippocampus of rat brain were compared. The data obtained in this study indicate the following: 1. Substance P stimulates the activities of (Na, K) and (Ca, Mg) ATPases more effectively in synaptosomal membranes from hippocampus than cerebral cortex. 2. Heptapeptide SP(5-11) (pyroGlu5, Tyr8) causes a more distinct increase of (Ca, Mg) ATPase activity in cortical synaptosomal membranes than SP does. 3. The change of L-Phe conformation to D in position 7 in hexapeptide induces reduction of enzymes activities in hippocampus. 4. Especially important for the maintenance of biological activity of drugs is the replacement of Gln5 with pyroGlu6 and conformation of Phe residues. 5. SP and shorter analogues of fragments SP C-terminal SP regulate the active cation transport in synaptosomal membranes of cerebral cortex and hippocampus.

Absolute quantitation of phosphorus metabolites in the cerebral cortex of the newborn human infant and in the forearm muscles of young adults using a double-tuned surface coil

NASA Astrophysics Data System (ADS)

Cady, Ernest B.

The application of a double-tuned surface coil with strong coupling for both 31P and 1H to the in vivo measurement of metabolite concentrations by NMR spectroscopy is demonstrated. It is shown that sample loading, although important for a coil tuned to a single frequency, does not necessarily have a significant effect on absolute quantitation results if the coil is strongly coupled to the sample for both nuclei. For the coil used in the present study, the spectrometer calibration coefficient is almost independent of loading and the 1H and 31P flip angles at the coil center produced by fixed length pulses could be arranged to be nearly equal over a range of loading conditions. In seven normal infants, of gestational plus postnatal age 35 to 37 weeks, the cerebral cortex nucleotide triphosphate concentration was 3.7 ± 0.6 m M/liter wet (mean ± SD). Metabolite concentrations were low in the cerebral cortex of a severely birth asphyxiated infant. The adenosine triphosphate concentration in the resting, fresh forearm muscles of six young adults was 6.3 ± 0.8 m M/liter wet.

Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.

2014-01-08

Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreasedmore » pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.« less

Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex

PubMed Central

Linninger, A. A.; Gould, I. G.; Marinnan, T.; Hsu, C.-Y.; Chojecki, M.; Alaraj, A.

2013-01-01

The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm3 subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection–diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty. PMID:23842693

Apigenin attenuates diabetes-associated cognitive decline in rats via suppressing oxidative stress and nitric oxide synthase pathway

PubMed Central

Mao, Xiao-Yuan; Yu, Jing; Liu, Zhao-Qian; Zhou, Hong-Hao

2015-01-01

Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway. PMID:26629041

[Effect of GABA, sodium glutamate and glycine on evoked potentials in the dental zones of the cerebral cortex].

PubMed

Degtiarev, V P

1979-01-01

Intraventricular administration of gamma-aminobutyric acid (GABA) and glycine decreased, whereas sodium glutamate increased the amplitude of primary responses of dental zones of the somatosensory cortex, which arose during electric stimulation of the pulp of the rabbit upper incisors. No changes in the latent periods were recorded.

Reduction of Na+, K+-ATPase activity and expression in cerebral cortex of glutaryl-CoA dehydrogenase deficient mice: a possible mechanism for brain injury in glutaric aciduria type I.

PubMed

Amaral, Alexandre Umpierrez; Seminotti, Bianca; Cecatto, Cristiane; Fernandes, Carolina Gonçalves; Busanello, Estela Natacha Brandt; Zanatta, Ângela; Kist, Luiza Wilges; Bogo, Maurício Reis; de Souza, Diogo Onofre Gomes; Woontner, Michael; Goodman, Stephen; Koeller, David M; Wajner, Moacir

2012-11-01

Mitochondrial dysfunction has been proposed to play an important role in the neuropathology of glutaric acidemia type I (GA I). However, the relevance of bioenergetics disruption and the exact mechanisms responsible for the cortical leukodystrophy and the striatum degeneration presented by GA I patients are not yet fully understood. Therefore, in the present work we measured the respiratory chain complexes activities I-IV, mitochondrial respiratory parameters state 3, state 4, the respiratory control ratio and dinitrophenol (DNP)-stimulated respiration (uncoupled state), as well as the activities of α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and Na+, K+-ATPase in cerebral cortex, striatum and hippocampus from 30-day-old Gcdh-/- and wild type (WT) mice fed with a normal or a high Lys (4.7%) diet. When a baseline (0.9% Lys) diet was given, we verified mild alterations of the activities of some respiratory chain complexes in cerebral cortex and hippocampus, but not in striatum from Gcdh-/- mice as compared to WT animals. Furthermore, the mitochondrial respiratory parameters and the activities of α-KGDH and CK were not modified in all brain structures from Gcdh-/- mice. In contrast, we found a significant reduction of Na(+), K(+)-ATPase activity associated with a lower degree of its expression in cerebral cortex from Gcdh-/- mice. Furthermore, a high Lys (4.7%) diet did not accentuate the biochemical alterations observed in Gcdh-/- mice fed with a normal diet. Since Na(+), K(+)-ATPase activity is required for cell volume regulation and to maintain the membrane potential necessary for a normal neurotransmission, it is presumed that reduction of this enzyme activity may represent a potential underlying mechanism involved in the brain swelling and cortical abnormalities (cortical atrophy with leukodystrophy) observed in patients affected by GA I. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring.

PubMed

Zhang, Tianliang; Zheng, Xinrui; Wang, Xia; Zhao, Hui; Wang, Tingting; Zhang, Hongxia; Li, Wanwei; Shen, Hua; Yu, Li

2018-01-16

Air pollution is a serious environmental health problem closely related to the occurrence of central nervous system diseases. Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM 2.5 ) during pregnancy may affect the growth and development of infants. The present study was to investigate the effects of maternal exposure to PM 2.5 during pregnancy on brain development in mice offspring. Pregnant mice were randomly divided into experimental groups of low-, medium-, or high-dosages of PM 2.5 , a mock-treated group which was treated with the same amount of phosphate buffer solution (PBS), and acontrol group which was untreated. The ethology of offspring mice on postnatal days 1, 7, 14, 21, and 30, along with neuronal development and apoptosis in the cerebral cortex were investigated. Compared with the control, neuronal mitochondrial cristae fracture, changed autophagy characteristics, significantly increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cell rate, and mRNA levels of apoptosis-related caspase-8 and caspase-9 were found in cerebral cortex of mice offspring from the treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased. Treatment groups also demonstrated enhanced protein expressions of apoptosis-related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with declined proliferating cell nuclear antigen (PCNA), Bcl-2, and ratio of Bcl-2 to Bax. Open field experiments and tail suspension experiments showed that exposure to high dosage of PM 2.5 resulted in decreased spontaneous activities but increased static accumulation time in mice offspring, indicating anxiety, depression, and social behavioral changes. Our results suggested that maternal exposure to PM 2.5 during pregnancy might interfere with cerebral cortex development in mice offspring by affecting cell apoptosis.

Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, Xia; Center for New Drugs Evaluation, Shandong University, Jinan 250012; Qu, Xian-Jun

Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at dosesmore » of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-{kappa}B p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 {+-} 0.7 to 1.2 {+-} 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-{kappa}B p65.« less

Abnormal Resting-State Functional Connectivity of the Anterior Cingulate Cortex in Unilateral Chronic Tinnitus Patients

PubMed Central

Chen, Yu-Chen; Liu, Shenghua; Lv, Han; Bo, Fan; Feng, Yuan; Chen, Huiyou; Xu, Jin-Jing; Yin, Xindao; Wang, Shukui; Gu, Jian-Ping

2018-01-01

Purpose: The anterior cingulate cortex (ACC) has been suggested to be involved in chronic subjective tinnitus. Tinnitus may arise from aberrant functional coupling between the ACC and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to illuminate the functional connectivity (FC) network of the ACC subregions in chronic tinnitus patients. Methods: Resting-state fMRI scans were obtained from 31 chronic right-sided tinnitus patients and 40 healthy controls (age, sex, and education well-matched) in this study. Rostral ACC and dorsal ACC were selected as seed regions to investigate the intrinsic FC with the whole brain. The resulting FC patterns were correlated with clinical tinnitus characteristics including the tinnitus duration and tinnitus distress. Results: Compared with healthy controls, chronic tinnitus patients showed disrupted FC patterns of ACC within several brain networks, including the auditory cortex, prefrontal cortex, visual cortex, and default mode network (DMN). The Tinnitus Handicap Questionnaires (THQ) scores showed positive correlations with increased FC between the rostral ACC and left precuneus (r = 0.507, p = 0.008) as well as the dorsal ACC and right inferior parietal lobe (r = 0.447, p = 0.022). Conclusions: Chronic tinnitus patients have abnormal FC networks originating from ACC to other selected brain regions that are associated with specific tinnitus characteristics. Resting-state ACC-cortical FC disturbances may play an important role in neuropathological features underlying chronic tinnitus. PMID:29410609

Optical coherence tomography for the quantitative study of cerebrovascular physiology

PubMed Central

Srinivasan, Vivek J; Atochin, Dmitriy N; Radhakrishnan, Harsha; Jiang, James Y; Ruvinskaya, Svetlana; Wu, Weicheng; Barry, Scott; Cable, Alex E; Ayata, Cenk; Huang, Paul L; Boas, David A

2011-01-01

Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range. PMID:21364599

Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence

PubMed Central

Massimini, Marcello; Postle, Bradley R.; Koch, Christof

2017-01-01

The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues. Dual Perspectives Companion Paper: Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?, by Brian Odegaard, Robert T. Knight, and Hakwan Lau PMID:28978697

Reelin is essential for neuronal migration but not for radial glial elongation in neonatal ferret cortex.

PubMed

Schaefer, Alisa; Poluch, Sylvie; Juliano, Sharon

2008-04-01

Numerous functions related to neuronal migration are linked to the glycoprotein reelin. Reelin also elongates radial glia, which are disrupted in mutant reeler mice. Our lab developed a model of cortical dysplasia in ferrets that shares features with the reeler mouse, including impaired migration of neurons into the cerebral cortex and disrupted radial glia. Explants of normal ferret cortex in coculture with dysplastic ferret cortex restore the deficits in this model. To determine if reelin is integral to the repair, we used explants of P0 mouse cortex either of the wild type (WT) or heterozygous (het) for the reelin gene, as well as P0 reeler cortex (not containing reelin), in coculture with organotypic cultures of dysplastic ferret cortex. This arrangement revealed that all types of mouse cortical explants (WT, het, reeler) elongated radial glia in ferret cortical dysplasia, indicating that reelin is not required for proper radial glial morphology. Migration of cells into ferret neocortex, however, did not improve with explants of reeler cortex, but was almost normal after pairing with WT or het explants. We also placed an exogenous source of reelin in ferret cultures at the pial surface to reveal that migrating cells move toward the reelin source in dysplastic cortex; radial glia in these cultures were also improved toward normal. Our results demonstrate that the normotopic position of reelin is important for proper neuronal positioning, and that reelin is capable of elongating radial glial cells but is not the only radialization factor.

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

PubMed Central

Zilles, Karl; Palomero-Gallagher, Nicola

2017-01-01

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas). Highlights Densities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints. PMID:28970785

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

PubMed Central

Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

2018-01-01

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating the microglial reaction in the peri-infarct cortex. PMID:29568282

Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet

PubMed Central

Bernier, Michel; Wahl, Devin; Ali, Ahmed; Allard, Joanne; Faulkner, Shakeela; Wnorowski, Artur; Sanghvi, Mitesh; Moaddel, Ruin; Alfaras, Irene; Mattison, Julie A.; Tarantini, Stefano; Tucsek, Zsuzsanna; Ungvari, Zoltan; Csiszar, Anna; Pearson, Kevin J.; de Cabo, Rafael

2016-01-01

Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress. PMID:27070252

Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet.

PubMed

Bernier, Michel; Wahl, Devin; Ali, Ahmed; Allard, Joanne; Faulkner, Shakeela; Wnorowski, Artur; Sanghvi, Mitesh; Moaddel, Ruin; Alfaras, Irene; Mattison, Julie A; Tarantini, Stefano; Tucsek, Zsuzsanna; Ungvari, Zoltan; Csiszar, Anna; Pearson, Kevin J; de Cabo, Rafael

2016-05-01

Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.

A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.

PubMed

Marbacher, Serge; Andereggen, Lukas; Neuschmelting, Volker; Widmer, Hans Rudolf; von Gunten, Michael; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2012-07-15

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells. SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%. The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Alterations of apparent diffusion coefficient (ADC) in the brain of rats chronically exposed to lead acetate.

PubMed

López-Larrubia, Pilar; Cauli, Omar

2011-03-15

Diffusion-weighted imaging (DWI) allows the assessment of the water apparent diffusion coefficient (ADC), a measure of tissue water diffusivity which is altered during different pathological conditions such as cerebral oedema. By means of DWI, we repeatedly measured in the same rats apparent diffusion coefficient ADC in different brain areas (motor cortex (MCx), somato-sensory cortex (SCx), caudate-putamen (CPu), hippocampus (Hip), mesencephalic reticular formation (RF), corpus callosum (CC) and cerebellum (Cb)) after 1 week, 4 and 12 weeks of lead acetate exposure via drinking water (50 or 500 ppm). After 12 weeks of lead exposure rats received albumin-Evans blue complex administration and were sacrificed 1h later. Blood-brain barrier permeability and water tissue content were determined in order to evaluate their relationship with ADC changes. Chronic exposure to lead acetate (500 ppm) for 4 weeks increased ADC values in Hip, RF and Cb but no in other brain areas. After 12 weeks of lead acetate exposure at 500 ppm ADC is significantly increased also in CPu and CC. Brain areas displaying high ADC values after lead exposure showed also an increased water content and increased BBB permeability to Evans blue-albumin complex. Exposure to 50 ppm for 12 weeks increased ADC values and BBB permeability in the RF and Cb. In summary, chronic lead exposure induces cerebral oedema in the adult brain depending on the brain area and the dose of exposure. RF and Cb appeared the most sensitive brain areas whereas cerebral cortex appears resistant to lead-induced cerebral oedema. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Mild Hypothermia Attenuates Mitochondrial Oxidative Stress by Protecting Respiratory Enzymes and Upregulating MnSOD in a Pig Model of Cardiac Arrest

PubMed Central

Gong, Ping; Li, Chun-Sheng; Hua, Rong; Zhao, Hong; Tang, Zi-Ren; Mei, Xue; Zhang, Ming-Yue; Cui, Juan

2012-01-01

Mild hypothermia is the only effective treatment confirmed clinically to improve neurological outcomes for comatose patients with cardiac arrest. However, the underlying mechanism is not fully elucidated. In this study, our aim was to determine the effect of mild hypothermia on mitochondrial oxidative stress in the cerebral cortex. We intravascularly induced mild hypothermia (33°C), maintained this temperature for 12 h, and actively rewarmed in the inbred Chinese Wuzhishan minipigs successfully resuscitated after 8 min of untreated ventricular fibrillation. Cerebral samples were collected at 24 and 72 h following return of spontaneous circulation (ROSC). We found that mitochondrial malondialdehyde and protein carbonyl levels were significantly increased in the cerebral cortex in normothermic pigs even at 24 h after ROSC, whereas mild hypothermia attenuated this increase. Moreover, mild hypothermia attenuated the decrease in Complex I and Complex III (i.e., major sites of reactive oxygen species production) activities of the mitochondrial respiratory chain and increased antioxidant enzyme manganese superoxide dismutase (MnSOD) activity. This increase in MnSOD activity was consistent with the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein expressions, and with the increase of Nrf2 nuclear translocation in normothermic pigs at 24 and 72 h following ROSC, whereas mild hypothermia enhanced these tendencies. Thus, our findings indicate that mild hypothermia attenuates mitochondrial oxidative stress in the cerebral cortex, which may be associated with reduced impairment of mitochondrial respiratory chain enzymes, and enhancement of MnSOD activity and expression via Nrf2 activation. PMID:22532848

Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

PubMed

Innes, Carrie R H; Kelly, Paul T; Hlavac, Michael; Melzer, Tracy R; Jones, Richard D

2015-05-01

To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). N/A. There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes. © 2015 Associated Professional Sleep Societies, LLC.

Cerebral morphology and dopamine D2/D3receptor distribution in humans: A combined [18F]fallypride and voxel-based morphometry study

PubMed Central

Woodward, Neil D.; Zald, David H.; Ding, Zhaohua; Riccardi, Patrizia; Ansari, M. Sib; Baldwin, Ronald M.; Cowan, Ronald L.; Li, Rui; Kessler, Robert M.

2009-01-01

The relationship between cerebral morphology and the expression of dopamine receptors has not been extensively studied in humans. Elucidation of such relationships may have important methodological implications for clinical studies of dopamine receptor ligand binding differences between control and patient groups. The association between cerebral morphology and dopamine receptor distribution was examined in 45 healthy subjects who completed T1-weighted structural MRI and PET scanning with the D2/D3 ligand [18F]fallypride. Optimized voxel-based morphometry was used to create grey matter volume and density images. Grey matter volume and density images were correlated with binding potential (BPND) images on a voxel-by-voxel basis using the Biological Parametric Mapping toolbox. Associations between cerebral morphology and BPND were also examined for selected regions-of-interest (ROIs) after spatial normalization. Voxel-wise analyses indicated that grey matter volume and density positively correlated with BPND throughout the midbrain, including the substantia nigra. Positive correlations were observed in medial cortical areas, including anterior cingulate and medial prefrontal cortex, and circumscribed regions of the temporal, frontal, and parietal lobes. ROI analyses revealed significant positive correlations between BPND and cerebral morphology in the caudate, thalamus, and amygdala. Few negative correlations between morphology and BPND were observed. Overall, grey matter density appeared more strongly correlated with BPND than grey matter volume. Cerebral morphology, particularly grey matter density, correlates with [18F]fallypride BPND in a regionally specific manner. Clinical studies comparing dopamine receptor availability between clinical and control groups may benefit by accounting for potential differences in cerebral morphology that exist even after spatial normalization. PMID:19457373

Cerebral morphology and dopamine D2/D3 receptor distribution in humans: a combined [18F]fallypride and voxel-based morphometry study.

PubMed

Woodward, Neil D; Zald, David H; Ding, Zhaohua; Riccardi, Patrizia; Ansari, M Sib; Baldwin, Ronald M; Cowan, Ronald L; Li, Rui; Kessler, Robert M

2009-05-15

The relationship between cerebral morphology and the expression of dopamine receptors has not been extensively studied in humans. Elucidation of such relationships may have important methodological implications for clinical studies of dopamine receptor ligand binding differences between control and patient groups. The association between cerebral morphology and dopamine receptor distribution was examined in 45 healthy subjects who completed T1-weighted structural MRI and PET scanning with the D(2)/D(3) ligand [(18)F]fallypride. Optimized voxel-based morphometry was used to create grey matter volume and density images. Grey matter volume and density images were correlated with binding potential (BP(ND)) images on a voxel-by-voxel basis using the Biological Parametric Mapping toolbox. Associations between cerebral morphology and BP(ND) were also examined for selected regions-of-interest (ROIs) after spatial normalization. Voxel-wise analyses indicated that grey matter volume and density positively correlated with BP(ND) throughout the midbrain, including the substantia nigra. Positive correlations were observed in medial cortical areas, including anterior cingulate and medial prefrontal cortex, and circumscribed regions of the temporal, frontal, and parietal lobes. ROI analyses revealed significant positive correlations between BP(ND) and cerebral morphology in the caudate, thalamus, and amygdala. Few negative correlations between morphology and BP(ND) were observed. Overall, grey matter density appeared more strongly correlated with BP(ND) than grey matter volume. Cerebral morphology, particularly grey matter density, correlates with [(18)F]fallypride BP(ND) in a regionally specific manner. Clinical studies comparing dopamine receptor availability between clinical and control groups may benefit by accounting for potential differences in cerebral morphology that exist even after spatial normalization.

Contribution of different regions of the prefrontal cortex and lesion laterality to deficit of decision-making on the Iowa Gambling Task.

PubMed

Ouerchefani, Riadh; Ouerchefani, Naoufel; Allain, Philippe; Ben Rejeb, Mohamed Riadh; Le Gall, Didier

2017-02-01

Few studies have examined the contribution of different sub-regions of the prefrontal cortex and lesion laterality to decision-making abilities. In addition, there are inconsistent findings about the role of ventromedial and dorsolateral lesions in decision-making deficit. In this study, decision-making processes are investigated following different damaged areas of the prefrontal cortex. We paid particular attention to the contribution of laterality, lesion location and lesion volume in decision-making deficit. Twenty-seven patients with discrete ventromedial lesions, dorsolateral lesions or extended-frontal lesions were compared with normal subjects on the Iowa Gambling Task (IGT). Our results showed that all frontal subgroups were impaired on the IGT in comparison with normal subjects. We noted also that IGT performance did not vary systematically based on lesion laterality or location. More precisely, our lesion analysis revealed that decision-making processes depend on a large cerebral network, including both ventromedial and dorsolateral areas of the prefrontal cortex. Consistent with past findings, our results support the claim that IGT deficit is not solitarily associated with ventromedial prefrontal cortex lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage

PubMed Central

Baron, Jean-Claude; Farid, Karim; Dolan, Eamon; Turc, Guillaume; Marrapu, Siva T; O'Brien, Eoin; Aigbirhio, Franklin I; Fryer, Tim D; Menon, David K; Warburton, Elizabeth A; Hong, Young T

2014-01-01

By detecting β-amyloid (Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (l-ICH). No previous study has directly assessed the diagnostic value of 11C-Pittsburgh compound B (PiB) PET in probable CAA-related l-ICH against healthy controls (HCs). 11C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic l-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity=91%, specificity=55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, 11C-PiB-PET has low specificity for CAA due to the frequent occurrence of high 11C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials. PMID:24619277

SO2 inhalation contributes to the development and progression of ischemic stroke in the brain.

PubMed

Sang, Nan; Yun, Yang; Li, Hongyan; Hou, Li; Han, Ming; Li, Guangke

2010-04-01

Epidemiological literatures show an association between air pollution and ischemic stroke, and effective pollutants may include SO(2), NO(x), O(3), CO, and particulates. However, existing experimental studies lack evidence as to the presence of effects for SO(2), which has been the focus in developing countries with increasing use of coal as the main resource. In the present study, we treated Wistar rats with SO(2) at various concentrations and determined endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule 1 (ICAM-1) messenger RNA (mRNA) and protein expression in the cortex. The results show that SO(2) elevated the levels of ET-1, iNOS, COX-2, and ICAM-1 mRNA and protein in a concentration-dependent manner. Then, we set up rat model of ischemic stroke using middle cerebral artery occlusion (MCAO) and further treated the model rats with filtered air and lower concentration SO(2) for the same period. As expected, elevated expression of ET-1, iNOS, COX-2, and ICAM-1 occurred in the cortex of MCAO model rats exposed to filtered air, followed by increased activation of caspase-3 and cerebral infarct volume. Interestingly, SO(2) inhalation after MCAO significantly amplified above effects. It implies that SO(2) inhalation caused brain injuries similar to that of cerebral ischemia, and its exposure in atmospheric environment contributed to the development and progression of ischemic stroke.

Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

PubMed

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

2017-04-01

Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristics of seizure-induced signal changes on MRI in patients with first seizures.

PubMed

Kim, Si Eun; Lee, Byung In; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Park, Kang Min; Kim, Hyung Chan; Lee, Joonwon; Bae, Soo-Young; Lee, Dongah; Kim, Sung Eun

2017-05-01

The aim of this study was to investigate the predictive factors and identify the characteristics of the seizure-induced signal changes on MRI (SCM) in patients with first seizures. We conducted a retrospective study of patients with first seizures from March 2010 to August 2014. The inclusion criteria for this study were patients with 1) first seizures, and 2) MRI and EEG performed within 24h of the first seizures. The definition of SCM was hyper-intensities in the brain not applying to cerebral arterial territories. Multivariate logistic regression was performed with or without SCM as a dependent variable. Of 431 patients with seizures visiting the ER, 69 patients met the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently significant variable predicting the presence of SCM in patients with first seizures. In addition, the topography of SCM was as follows; i) ipsilateral hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11), iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus (1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI exhibited unilateral cortical hyperperfusion with ipsilateral thalamic involvement reflecting unrestricted vascular territories. There is an association between epileptiform discharges and SCM. Additionally, the involvement of the unilateral cortex and ipsilateral thalamus in SCM and its hyperperfusion state could be helpful in differentiating the consequences of epileptic seizures from other pathologies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Vestibular signals in primate cortex for self-motion perception.

PubMed

Gu, Yong

2018-04-21

The vestibular peripheral organs in our inner ears detect transient motion of the head in everyday life. This information is sent to the central nervous system for automatic processes such as vestibulo-ocular reflexes, balance and postural control, and higher cognitive functions including perception of self-motion and spatial orientation. Recent neurophysiological studies have discovered a prominent vestibular network in the primate cerebral cortex. Many of the areas involved are multisensory: their neurons are modulated by both vestibular signals and visual optic flow, potentially facilitating more robust heading estimation through cue integration. Combining psychophysics, computation, physiological recording and causal manipulation techniques, recent work has addressed both the encoding and decoding of vestibular signals for self-motion perception. Copyright © 2018. Published by Elsevier Ltd.

Decreased cerebral blood flow of the right anterior cingulate cortex in long-term and short-term abstinent methamphetamine users.

PubMed

Hwang, Jaeuk; Lyoo, In Kyoon; Kim, Seog Ju; Sung, Young Hoon; Bae, Soojeong; Cho, Sung-Nam; Lee, Ho Young; Lee, Dong Soo; Renshaw, Perry F

2006-04-28

The aim of the current study was to explore changes of relative regional cerebral blood flow (rCBF) in short-term and long-term abstinent methamphetamine (MA) users. Relative rCBF in 40 abstinent MA users and 23 healthy comparison subjects was compared by the technetium-99m-hexamethyl-propylene amine oxime ((99m)Tc-HMPAO) single photon emission computed tomography (SPECT). Relative rCBF in areas that were found to differ significantly was also compared in groups of MA users with short-term (<6 months) and long-term (>or=6 months) abstinence. MA users showed decreased relative rCBF in the right anterior cingulate cortex (Brodmann area 32) relative to healthy comparison subjects. Long-term abstinent MA users had significantly greater rCBF than short-term abstinent MA users. We report that abstinent MA users have decreased rCBF in the anterior cingulate cortex with smaller relative decreases in subjects with prolonged abstinence.

Effects of neonatal medial versus lateral temporal cortex injury: theoretical comment on Malkova et al. (2010).

PubMed

Kolb, Bryan

2010-12-01

The article by Malkova, Mishkin, Suomo, and Bachevalier (2010, this issue) adds an important piece to our understanding of the role of the medial versus lateral temporal regions in socioemotional behavior. In their paper, they evaluate the effect of infant and adult amygdala lesions and infant inferotemporal cortex lesions on the social interactions of monkeys in infancy and adulthood. The results show that medial temporal lesions performed in infants produce greater effects on socioaffective behavior than similar lesions in adulthood and that infant monkeys with inferotemporal lesions exhibit social deficits that are resolved by adulthood. These results are relevant to three significant issues: (1) the role of the medial temporal and lateral temporal cortex in the symptoms of the Kluver-Bucy syndrome; (2) the role of age at injury in behavioral change after cerebral injuries; and (3) the importance of lesion locus and behavioral measure for recovery from infant and adult cerebral injury. © 2010 APA, all rights reserved.

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice.

PubMed

Yang, Yue; Aloi, Macarena S; Cudaback, Eiron; Josephsen, Samuel R; Rice, Samantha J; Jorstad, Nikolas L; Keene, C Dirk; Montine, Thomas J

2014-11-01

Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow (BM)-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes BM-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn(+/+) (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin-deficient (Grn(-/-)) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn(-/-) mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn(-/-) mice that was partially to fully reversed 5 months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases.

An integrated software suite for surface-based analyses of cerebral cortex.

PubMed

Van Essen, D C; Drury, H A; Dickson, J; Harwell, J; Hanlon, D; Anderson, C H

2001-01-01

The authors describe and illustrate an integrated trio of software programs for carrying out surface-based analyses of cerebral cortex. The first component of this trio, SureFit (Surface Reconstruction by Filtering and Intensity Transformations), is used primarily for cortical segmentation, volume visualization, surface generation, and the mapping of functional neuroimaging data onto surfaces. The second component, Caret (Computerized Anatomical Reconstruction and Editing Tool Kit), provides a wide range of surface visualization and analysis options as well as capabilities for surface flattening, surface-based deformation, and other surface manipulations. The third component, SuMS (Surface Management System), is a database and associated user interface for surface-related data. It provides for efficient insertion, searching, and extraction of surface and volume data from the database.

Effects of analogues of substance P fragments on the MAO activity in rat brain.

PubMed

Turska, E; Lachowicz, L; Koziołkiewicz, W; Wasiak, T

1985-01-01

The influence in vitro of analogues of Sp5-11 and SP6-11 substance P fragments on the activity of monoamine oxidase (MAO) in homogenates and crude mitochondrial fractions of rat brain was examined. The rat brain was divided into: I--cerebral cortex, II--hippocampus, III--midbrain, IV--thalamus with hypothalamus, V--cerebellum and VI--medulla oblongata. The obtained results proved that the analogues of SP fragments inhibit selectively the activity of the enzyme in the homogenates of cerebral cortex, hippocampus, midbrain and cerebellum. In the crude mitochondrial fractions the applied analogues of SP fragments caused a slight increase of the enzyme activity. The most significant changes in the activity of MAO were observed in hippocampus homogenate fraction.

An integrated software suite for surface-based analyses of cerebral cortex

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.; Dickson, J.; Harwell, J.; Hanlon, D.; Anderson, C. H.

2001-01-01

The authors describe and illustrate an integrated trio of software programs for carrying out surface-based analyses of cerebral cortex. The first component of this trio, SureFit (Surface Reconstruction by Filtering and Intensity Transformations), is used primarily for cortical segmentation, volume visualization, surface generation, and the mapping of functional neuroimaging data onto surfaces. The second component, Caret (Computerized Anatomical Reconstruction and Editing Tool Kit), provides a wide range of surface visualization and analysis options as well as capabilities for surface flattening, surface-based deformation, and other surface manipulations. The third component, SuMS (Surface Management System), is a database and associated user interface for surface-related data. It provides for efficient insertion, searching, and extraction of surface and volume data from the database.

Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type.

PubMed

Pilz, Gregor-Alexander; Shitamukai, Atsunori; Reillo, Isabel; Pacary, Emilie; Schwausch, Julia; Stahl, Ronny; Ninkovic, Jovica; Snippert, Hugo J; Clevers, Hans; Godinho, Leanne; Guillemot, Francois; Borrell, Victor; Matsuzaki, Fumio; Götz, Magdalena

2013-01-01

The mechanisms governing the expansion of neuron number in specific brain regions are still poorly understood. Enlarged neuron numbers in different species are often anticipated by increased numbers of progenitors dividing in the subventricular zone. Here we present live imaging analysis of radial glial cells and their progeny in the ventral telencephalon, the region with the largest subventricular zone in the murine brain during neurogenesis. We observe lineage amplification by a new type of progenitor, including bipolar radial glial cells dividing at subapical positions and generating further proliferating progeny. The frequency of this new type of progenitor is increased not only in larger clones of the mouse lateral ganglionic eminence but also in cerebral cortices of gyrated species, and upon inducing gyrification in the murine cerebral cortex. This implies key roles of this new type of radial glia in ontogeny and phylogeny.

Corticocortical evoked potentials reveal projectors and integrators in human brain networks.

PubMed

Keller, Corey J; Honey, Christopher J; Entz, Laszlo; Bickel, Stephan; Groppe, David M; Toth, Emilia; Ulbert, Istvan; Lado, Fred A; Mehta, Ashesh D

2014-07-02

The cerebral cortex is composed of subregions whose functional specialization is largely determined by their incoming and outgoing connections with each other. In the present study, we asked which cortical regions can exert the greatest influence over other regions and the cortical network as a whole. Previous research on this question has relied on coarse anatomy (mapping large fiber pathways) or functional connectivity (mapping inter-regional statistical dependencies in ongoing activity). Here we combined direct electrical stimulation with recordings from the cortical surface to provide a novel insight into directed, inter-regional influence within the cerebral cortex of awake humans. These networks of directed interaction were reproducible across strength thresholds and across subjects. Directed network properties included (1) a decrease in the reciprocity of connections with distance; (2) major projector nodes (sources of influence) were found in peri-Rolandic cortex and posterior, basal and polar regions of the temporal lobe; and (3) major receiver nodes (receivers of influence) were found in anterolateral frontal, superior parietal, and superior temporal regions. Connectivity maps derived from electrical stimulation and from resting electrocorticography (ECoG) correlations showed similar spatial distributions for the same source node. However, higher-level network topology analysis revealed differences between electrical stimulation and ECoG that were partially related to the reciprocity of connections. Together, these findings inform our understanding of large-scale corticocortical influence as well as the interpretation of functional connectivity networks. Copyright © 2014 the authors 0270-6474/14/349152-12$15.00/0.

In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

PubMed

Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

2017-05-01

Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Principles of ipsilateral and contralateral cortico-cortical connectivity in the mouse.

PubMed

Goulas, Alexandros; Uylings, Harry B M; Hilgetag, Claus C

2017-04-01

Structural connectivity among cortical areas provides the substrate for information exchange in the cerebral cortex and is characterized by systematic patterns of presence or absence of connections. What principles govern this cortical wiring diagram? Here, we investigate the relation of physical distance and cytoarchitecture with the connectional architecture of the mouse cortex. Moreover, we examine the relation between patterns of ipsilateral and contralateral connections. Our analysis reveals a mirrored and attenuated organization of contralateral connections when compared with ipsilateral connections. Both physical distance and cytoarchitectonic similarity of cortical areas are related to the presence or absence of connections. Notably, our analysis demonstrates that the combination of these factors relates better to cortico-cortical connectivity than each factor in isolation and that the two factors relate differently to ipsilateral and contralateral connectivity. Physical distance is more tightly related to the presence or absence of ipsilateral connections, but its relevance greatly diminishes for contralateral connections, while the contribution of cytoarchitectonic similarity remains relatively stable. Our results, together with similar findings in the cat and macaque cortex, suggest that a common set of principles underlies the macroscale wiring of the mammalian cerebral cortex.

Bilateral recruitment of prefrontal cortex in working memory is associated with task demand but not with age

PubMed Central

Höller-Wallscheid, Melanie S.; Thier, Peter; Pomper, Jörn K.; Lindner, Axel

2017-01-01

Elderly adults may master challenging cognitive demands by additionally recruiting the cross-hemispheric counterparts of otherwise unilaterally engaged brain regions, a strategy that seems to be at odds with the notion of lateralized functions in cerebral cortex. We wondered whether bilateral activation might be a general coping strategy that is independent of age, task content and brain region. While using functional magnetic resonance imaging (fMRI), we pushed young and old subjects to their working memory (WM) capacity limits in verbal, spatial, and object domains. Then, we compared the fMRI signal reflecting WM maintenance between hemispheric counterparts of various task-relevant cerebral regions that are known to exhibit lateralization. Whereas language-related areas kept their lateralized activation pattern independent of age in difficult tasks, we observed bilaterality in dorsolateral and anterior prefrontal cortex across WM domains and age groups. In summary, the additional recruitment of cross-hemispheric counterparts seems to be an age-independent domain-general strategy to master cognitive challenges. This phenomenon is largely confined to prefrontal cortex, which is arguably less specialized and more flexible than other parts of the brain. PMID:28096364

Therapeutic effects of various methods of MSC transplantation on cerebral resuscitation following cardiac arrest in rats

PubMed Central

LEONG, KA-HONG; ZHOU, LI-LI; LIN, QING-MING; WANG, PENG; YAO, LAN; HUANG, ZI-TONG

2016-01-01

In the present study, mesenchymal stem cells (MSCs) were transplanted into the brain of rats following cardiopulmonary resuscitation (CPR) by three different methods: Direct stereotaxic injection into the lateral cerebral ventricle (LV), intra-carotid administration (A), and femoral venous infusion (V). The three different methods were compared by observing the effects of MSCs on neurological function following global cerebral hypoxia-ischemia, in order to determine the optimum method for MSC transplantation. MSCs were transplanted in groups A, V and LV following the restoration of spontaneous circulation. Neurological deficit scale scores were higher in the transplantation groups, as compared with the control group. Neuronal damage, brain water content and serum levels of S100 calcium-binding protein B were reduced in the hippo-campus and temporal cortex of the transplantation groups, as compared with the control rats following resuscitation. MSCs were able to migrate inside the brain tissue following transplantation, and were predominantly distributed in the hippocampus and temporal cortex where the neurons were vulnerable during global cerebral ischemia. These results suggest that transplantation of MSCs may notably improve neurological function following CPR in a rat model. Of the three different methods of MSC transplantation tested in the present study, LV induced the highest concentration of MSCs in brain areas vulnerable to global cerebral ischemia, and therefore, produced the best neurological outcome. PMID:26935023

Gray-matter structural variability in the human cerebellum: Lobule-specific differences across sex and hemisphere.

PubMed

Steele, Christopher J; Chakravarty, M Mallar

2018-04-15

Though commonly thought of as a "motor structure", we now know that the cerebellum's reciprocal connections to the cerebral cortex underlie contributions to both motor and non-motor behavior. Further, recent research has shown that cerebellar dysfunction may contribute to a wide range of neuropsychiatric disorders. However, there has been little characterization of normative variability at the level of cerebellar structure that can facilitate and further our understanding of disease biomarkers. In this manuscript we examine normative variation of the cerebellum using data from the Human Connectome Project (HCP). The Multiple Automatically Generated Templates (MAGeT) segmentation tool was used to identify the cerebella and 33 anatomically-defined lobules from 327 individuals from the HCP. To characterize normative variation, we estimated population mean volume and variability, assessed differences in hemisphere and sex, and related lobular volume to motor and non-motor behavior. We found that the effects of hemisphere and sex were not homogeneous across all lobules of the cerebellum. Greater volume in the right hemisphere was primarily driven by lobules Crus I, II, and H VIIB, with H VIIIA exhibiting the greatest left>right asymmetry. Relative to total cerebellar gray-matter volume, females had larger Crus II (known to be connected with non-motor regions of the cerebral cortex) while males had larger motor-connected lobules including H V, and VIIIA/B. When relating lobular volume to memory, motor performance, and emotional behavior, we found some evidence for relationships that have previously been identified in the literature. Our observations of normative cerebellar structure and variability in young adults provide evidence for lobule-specific differences in volume and the relationship with sex and behavior - indicating that the cerebellum cannot be considered a single structure with uniform function, but as a set of regions with functions that are likely as diverse as their connectivity with the cerebral cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

PubMed

Banerjee, S; Poddar, M K

2016-04-05

Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

PubMed

Delwing-de Lima, Daniela; Fröhlich, Monique; Dalmedico, Leticia; Aurélio, Juliana Gruenwaldt Maia; Delwing-Dal Magro, Débora; Pereira, Eduardo Manoel; Wyse, Angela T S

2017-04-01

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

PubMed

Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

2013-03-01

We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

PubMed

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

PubMed Central

Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

2011-01-01

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

Modeling fluid diffusion in cerebral white matter with random walks in complex environments

NASA Astrophysics Data System (ADS)

Levy, Amichai; Cwilich, Gabriel; Buldyrev, Sergey V.; Weeden, Van J.

2012-02-01

Recent studies with diffusion MRI have shown new aspects of geometric order in the brain, including complex path coherence within the cerebral cortex, and organization of cerebral white matter and connectivity across multiple scales. The main assumption of these studies is that water molecules diffuse along myelin sheaths of neuron axons in the white matter and thus the anisotropy of their diffusion tensor observed by MRI can provide information about the direction of the axons connecting different parts of the brain. We model the diffusion of particles confined in the space of between the bundles of cylindrical obstacles representing fibrous structures of various orientations. We have investigated the directional properties of the diffusion, by studying the angular distribution of the end point of the random walks as a function of their length, to understand the scale over which the distribution randomizes. We will show evidence of qualitative change in the behavior of the diffusion for different volume fractions of obstacles. Comparisons with three-dimensional MRI images will be illustrated.

Embolic stroke associated with injection of buprenorphine tablets.

PubMed

Lim, C C Tchoyoson; Lee, Sze Haur; Wong, Yee-Choon; Hui, Francis

2009-09-15

Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets. Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed. Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery. Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kajimoto, Masaki; Ledee, Dolena R.; Olson, Aaron K.

Rationale: Deep hypothermic circulatory arrest (DHCA) is often required for the repair of complex congenital cardiac defects in infants. However, DHCA induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion (SCP) theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. Objectives: We tested the hypothesis that SCP modulates glucose entry into the citric acid cycle, and ameliorates abnormalities in glutamate flux which occur in association neuroapoptosis during DHCA. Methods and Results: Eighteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups of 7 (DHCA or DHCAmore » with SCP for 60 minutes at 18 °C) and 4 control pigs without cardiopulmonary bypass support. After the completion of rewarming from DHCA, 13-Carbon-labeled (13C) glucose as a metabolic tracer was infused. We used gas chromatography-mass spectrometry (GCMS) and nuclear magnetic resonance for metabolic analysis in the frontal cortex. Following 2.5 hours of cerebral reperfusion, we observed similar cerebral ATP levels, absolute levels of lactate and citric acid cycle intermediates, and 13C-enrichment. However, DHCA induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid (GABA)/glutamate along with neuroapoptosis (TUNEL), which were all prevented by SCP. Conclusions: DHCA alone induces abnormalities in cycling of the major neurotransmitters in association with neuroapoptosis, but does not alter cerebral glucose utilization during reperfusion. The data suggest that SCP prevents these modifications in glutamate/glutamine/GABA cycling and protects the cerebral cortex from neuroapoptosis.« less

Combined treatment of methylprednisolone pulse and memantine hydrochloride prompts recovery from neurological dysfunction and cerebral hypoperfusion in carbon monoxide poisoning: a case report.

PubMed

Iwamoto, Konosuke; Ikeda, Ken; Mizumura, Sunao; Tachiki, Kazuhiro; Yanagihashi, Masaru; Iwasaki, Yasuo

2014-03-01

A 49-year-old healthy man developed sudden unconsciousness under inadequate ventilation. Blood gas analysis showed carboxyhemoglobin of 7.3%. After normobaric oxygen therapy, he recovered completely 7 days later. At 3 weeks after carbon monoxide (CO) exposures, memory and gait disturbances appeared. Neurological examination revealed Mini-Mental State Examination (MMSE) score of 5 of 30 points, leg hyper-reflexia with Babinski signs, and Parkinsonism. Brain fluid-attenuated inversion recovery imaging disclosed symmetric hypointense lesions in the thalamus and the globus pallidus, and hyperintense lesions in the cerebral white matter. Brain single-photon emission tomography (SPECT) scanning with (99m)Technesium-ethyl cysteinate dimer displayed marked hypoperfusion in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. He was diagnosed as CO poisoning and treated with hyperbaric oxygen therapy. The neurological deficits were not ameliorated. At 9 weeks after neurological onset, methylprednisolone (1000 mg/day, intravenous, 3 days) and memantine hydrochloride (20 mg/day, per os) were administered. Three days later, MMSE score was increased from 3 to 20 points. Neurological examination was normal 3 weeks later. Brain SPECT exhibited 20% increase of regional cerebral blood flows in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. These clinicoradiological changes supported that the treatment with steroid pulse and memantine hydrochloride could prompt recovery from neurological dysfunction and cerebral hypoperfusion. Further clinical trials are warranted whether such combined therapy can attenuate neurological deficits and cerebral hypoperfusion in patients with CO poisoning. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Orbitofrontal cortex mediates pain inhibition by monetary reward.

PubMed

Becker, Susanne; Gandhi, Wiebke; Pomares, Florence; Wager, Tor D; Schweinhardt, Petra

2017-04-01

Pleasurable stimuli, including reward, inhibit pain, but the level of the neuraxis at which they do so and the cerebral processes involved are unknown. Here, we characterized a brain circuitry mediating pain inhibition by reward. Twenty-four healthy participants underwent functional magnetic resonance imaging while playing a wheel of fortune game with simultaneous thermal pain stimuli and monetary wins or losses. As expected, winning decreased pain perception compared to losing. Inter-individual differences in pain modulation by monetary wins relative to losses correlated with activation in the medial orbitofrontal cortex (mOFC). When pain and reward occured simultaneously, mOFCs functional connectivity changed: the signal time course in the mOFC condition-dependent correlated negatively with the signal time courses in the rostral anterior insula, anterior-dorsal cingulate cortex and primary somatosensory cortex, which might signify moment-to-moment down-regulation of these regions by the mOFC. Monetary wins and losses did not change the magnitude of pain-related activation, including in regions that code perceived pain intensity when nociceptive input varies and/or receive direct nociceptive input. Pain inhibition by reward appears to involve brain regions not typically involved in nociceptive intensity coding but likely mediate changes in the significance and/or value of pain. © The Author (2017). Published by Oxford University Press.

Effect of transcranial direct-current stimulation combined with treadmill training on balance and functional performance in children with cerebral palsy: a double-blind randomized controlled trial.

PubMed

Duarte, Natália de Almeida Carvalho; Grecco, Luanda André Collange; Galli, Manuela; Fregni, Felipe; Oliveira, Cláudia Santos

2014-01-01

Cerebral palsy refers to permanent, mutable motor development disorders stemming from a primary brain lesion, causing secondary musculoskeletal problems and limitations in activities of daily living. The aim of the present study was to determine the effects of gait training combined with transcranial direct-current stimulation over the primary motor cortex on balance and functional performance in children with cerebral palsy. A double-blind randomized controlled study was carried out with 24 children aged five to 12 years with cerebral palsy randomly allocated to two intervention groups (blocks of six and stratified based on GMFCS level (levels I-II or level III).The experimental group (12 children) was submitted to treadmill training and anodal stimulation of the primary motor cortex. The control group (12 children) was submitted to treadmill training and placebo transcranial direct-current stimulation. Training was performed in five weekly sessions for 2 weeks. Evaluations consisted of stabilometric analysis as well as the administration of the Pediatric Balance Scale and Pediatric Evaluation of Disability Inventory one week before the intervention, one week after the completion of the intervention and one month after the completion of the intervention. All patients and two examiners were blinded to the allocation of the children to the different groups. The experimental group exhibited better results in comparison to the control group with regard to anteroposterior sway (eyes open and closed; p<0.05), mediolateral sway (eyes closed; p<0.05) and the Pediatric Balance Scale both one week and one month after the completion of the protocol. Gait training on a treadmill combined with anodal stimulation of the primary motor cortex led to improvements in static balance and functional performance in children with cerebral palsy. Ensaiosclinicos.gov.br/RBR-9B5DH7.

Factors influencing frontal cortex development and recovery from early frontal injury.

PubMed

Halliwell, Celeste; Comeau, Wendy; Gibb, Robbin; Frost, Douglas O; Kolb, Bryan

2009-01-01

Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Although most cortical regions are sensitive to a wide range of experiential factors during development and later in life, the prefrontal cortex appears to be unusually sensitive to perinatal experiences and relatively immune to many adulthood experiences relative to other neocortical regions. One way to examine experience-dependent prefrontal development is to conduct studies in which experiential perturbations are related neuronal morphology. This review of the research reveals both pre- and post-natal factors have important effects on prefrontal development and behaviour. Such factors include psychoactive drugs, including both illicit drugs and prescription drugs, stress, gonadal hormones and sensory and motor stimulation. A second method of study is to examine both the effects of perinatal prefrontal injury on the development of the remaining cerebral mantle and correlated behaviours as well as the effects of post-injury rehabilitation programmes on the anatomical and behavioural measures. Prefrontal injury alters cerebral development in a developmental-stage dependent manner with perinatal injuries having far more deleterious effects than similar injuries later in infancy. The outcome of perinatal injuries can be modified, however, by rehabilitation with many of the factors shown to influence prefrontal development in the otherwise normal brain.

ADNP: in search for molecular mechanisms and innovative therapeutic strategies for frontotemporal degeneration

PubMed Central

Gozes, Illana; Ivashko-Pachima, Yanina

2015-01-01

Activity-dependent neuroprotective protein (ADNP) is deregulated in Alzheimer's disease (AD) and in schizophrenia and mutated in autism. In mice, ADNP is essential for brain formation and ADNP haploinsufficiency is associated with cognitive and social deficits and tauopathy. Tauopathy, a major pathology in AD, is also found in ~45% of frontotemporal dementias (FTDs). Tau transcript, a product of a single gene, undergoes alternative splicing. Tau splicing seems to be altered in FTD brain. In transgenic mice overexpressing a mutated tau in the cerebral cortex, significant increases in ADNP transcript expression were observed in the cerebral cortex of young transgenic mice (~disease onset) and a marked decrease with aging as compared to control littermates. ADNP is a member of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex also associated with alternative splicing, including tau transcript splicing. Further cellular interactions of ADNP include association with microtubules, with tau being a microtubule—associated protein. NAP (davundetide), a novel drug candidate derived from ADNP, increases ADNP-microtubule association and protects against tauopathy and cognitive deficiencies in mice. Although, NAP did not provide protection in progressive supranuclear palsy (PSP), a pure tauopathy, it increased cognitive scores in amnestic mild cognitively impaired patients and protected functional activity in schizophrenia patients. This mini-review focuses on ADNP in the context of FTD and tau/microtubules and proposes NAP as a novel drug target for future clinical evaluations. PMID:26578950

An experimental model for the study of cognitive disorders: the hippocampus and associative learning in mice.

PubMed

Delgado-García, José M; Gruart, Agnès

2008-12-01

The availability of transgenic mice mimicking selective human neurodegenerative and psychiatric disorders calls for new electrophysiological and microstimulation techniques capable of being applied in vivo in this species. In this article, we will concentrate on experiments and techniques developed in our laboratory during the past few years. Thus we have developed different techniques for the study of learning and memory capabilities of wild-type and transgenic mice with deficits in cognitive functions, using classical conditioning procedures. These techniques include different trace (tone/SHOCK and shock/SHOCK) conditioning procedures ? that is, a classical conditioning task involving the cerebral cortex, including the hippocampus. We have also developed implantation and recording techniques for evoking long-term potentiation (LTP) in behaving mice and for recording the evolution of field excitatory postsynaptic potentials (fEPSP) evoked in the hippocampal CA1 area by the electrical stimulation of the commissural/Schaffer collateral pathway across conditioning sessions. Computer programs have also been developed to quantify the appearance and evolution of eyelid conditioned responses and the slope of evoked fEPSPs. According to the present results, the in vivo recording of the electrical activity of selected hippocampal sites during classical conditioning of eyelid responses appears to be a suitable experimental procedure for studying learning capabilities in genetically modified mice, and an excellent model for the study of selected neuropsychiatric disorders compromising cerebral cortex functioning.

Clinical values of intraoperative indocyanine green fluorescence video angiography with Flow 800 software in cerebrovascular surgery.

PubMed

Ye, Xun; Liu, Xing-Ju; Ma, Li; Liu, Ling-Tong; Wang, Wen-Lei; Wang, Shuo; Cao, Yong; Zhang, Dong; Wang, Rong; Zhao, Ji-Zong; Zhao, Yuan-Li

2013-11-01

Microscope-integrated near-infrared indocyanine green video angiography (ICG-VA) has been used in neurosurgery for a decade. This study aimed to assess the value of intraoperative indocyanine green (ICG) video angiography with Flow 800 software in cerebrovascular surgery and to discover its hemodynamic features and changes of cerebrovascular diseases during surgery. A total of 87 patients who received ICG-VA during various surgical procedures were enrolled in this study. Among them, 45 cases were cerebral aneurysms, 25 were cerebral arteriovenous malformations (AVMs), and 17 were moyamoya disease (MMD). A surgical microscope integrating an infrared fluorescence module was used to confirm the residual aneurysms and blocking of perforating arteries in aneurysms. Feeder arteries, draining veins, and normal cortical vessels were identified by the time delay color mode of Flow 800 software. Hemodynamic parameters were recorded. All data were analyzed by SPSS version 18.0 (SPSS Inc., USA). T-test was used to analyze the hemodynamic features of AVMs and MMDs, the influence on peripheral cortex after resection in AVMs, and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in MMDs. The visual delay map obtained by Flow 800 software had more advantages than the traditional playback mode in identifying the feeder arteries, draining veins, and their relations to normal cortex vessels. The maximum fluorescence intensity (MFI) and the slope of ICG fluorescence curve of feeder arteries and draining veins were higher than normal peripheral vessels (MFI: 584.24±85.86 vs. 382.94 ± 91.50, slope: 144.95 ± 38.08 vs. 69.20 ± 13.08, P < 0.05). The arteriovenous transit time in AVM was significantly shorter than in normal cortical vessels ((0.60 ± 0.27) vs. (2.08 ± 1.42) seconds, P < 0.05). After resection of AVM, the slope of artery in the cortex increased, which reflected the increased cerebral flow. In patients with MMD, after STA-MCA bypass, cortex perfusion of corresponding branches region increased and local cycle time became shorter. Intraoperative ICG video angiography combined with hemodynamic parameter analysis obtained by Flow 800 software appears to be useful for intraoperative monitoring of regional cerebral blood flow in cerebrovascular disease.

Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E ("Europa").

PubMed

Sacks, Justin; Ray, M Jordan; Williams, Sue; Opatowsky, Michael J

2012-10-01

We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or "Europa." Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer "designer" psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We describe magnetic resonance imaging (MRI) findings to include selective diffuse toxic injury of the cerebral white matter with sparing of the cortex and most of the deep gray nuclei. To our knowledge, this is the first reported description of cerebral findings on MRI that are likely related to a lethal ingestion of 2C-E.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

PubMed

Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway.

PubMed

Zhang, Fan; Chen, Jian; Lin, Xinyue; Peng, Shiqiao; Yu, Xiaohui; Shan, Zhongyan; Teng, Weiping

2018-05-01

Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH) on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Female adult Wistar rats were randomly divided into three groups ( n  = 15 per group): control (CON) group, SCH group and overt hypothyroidism (OH) group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP) and Morris water-maze (MWM) test. The protein expression of the p75 neurotrophin receptor (p75 NTR ), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting. The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75 NTR , p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex. © 2018 The authors.

Different effects of transcutaneous electric nerve stimulation and electroacupuncture at ST36–ST37 on the cerebral cortex

PubMed Central

Kang, Yu-Tien; Liao, Yi-Sheng; Hsieh, Ching-Liang

2015-01-01

Background The effects of transcutaneous electric nerve stimulation (TENS) and electroacupuncture (EA) on the cerebral cortex are largely unclear. The purpose of the present study was to investigate the effect of TENS and EA on the cerebral cortex by examining their effect on the median nerve-somatosensory evoked potentials (MN-SEPs). Methods Twenty volunteers were studied. The cortical and cervical spinal potentials were recorded by median nerve stimulation at the left wrist. Sham TENS, 2 Hz TENS and 2 Hz EA were applied to both ST36 and ST37. MN-SEPs were recorded during sham TENS, 2 Hz TENS and 2 Hz EA, with at least 1 week interval for each subject. One-way analysis of variance was used to determine the differences in latency and amplitude of the MN-SEPs observed in the stimulation and post-stimulation periods compared with baseline. Scheffe's post hoc correction was employed to identify pairwise differences. Results No differences in mean latency were found between the stimulation procedures during the stimulation and post-stimulation periods. 2 Hz EA but not sham TENS or 2 Hz TENS caused higher mean amplitudes in N20 and N30 during the stimulation and post-stimulation periods. Conclusions EA, but not TENS, induces changes in certain components of the signal. PMID:25432425

Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring

PubMed Central

Wang, Yanyan; Surzenko, Natalia; Friday, Walter B.; Zeisel, Steven H.

2015-01-01

Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline supply between embryonic day (E)11 and E17 of gestation, the number of 2 types of cortical neural progenitor cells (NPCs)—radial glial cells and intermediate progenitor cells—was reduced in fetal brains (P < 0.01). Furthermore, the number of upper layer cortical neurons was decreased in the offspring of dams fed an LC diet at both E17 (P < 0.001) and 4 mo of age (P < 0.001). These effects of LC maternal diet were mediated by a decrease in epidermal growth factor receptor (EGFR) signaling in NPCs related to the disruption of EGFR posttranscriptional regulation. Our findings describe a novel mechanism whereby low maternal dietary intake of choline alters brain development.—Wang, Y., Surzenko, N., Friday, W. B., Zeisel, S. H. Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring. PMID:26700730

Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

PubMed

Wang, Yanyan; Surzenko, Natalia; Friday, Walter B; Zeisel, Steven H

2016-04-01

Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline supply between embryonic day (E)11 and E17 of gestation, the number of 2 types of cortical neural progenitor cells (NPCs)-radial glial cells and intermediate progenitor cells-was reduced in fetal brains (P< 0.01). Furthermore, the number of upper layer cortical neurons was decreased in the offspring of dams fed an LC diet at both E17 (P< 0.001) and 4 mo of age (P< 0.001). These effects of LC maternal diet were mediated by a decrease in epidermal growth factor receptor (EGFR) signaling in NPCs related to the disruption of EGFR posttranscriptional regulation. Our findings describe a novel mechanism whereby low maternal dietary intake of choline alters brain development.-Wang, Y., Surzenko, N., Friday, W. B., Zeisel, S. H. Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring. © FASEB.

Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

PubMed Central

Holmes, Ben; Jung, Seung Ho; Lu, Jing; Wagner, Jessica A.; Rubbi, Liudmilla; Pellegrini, Matteo

2016-01-01

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied. PMID:28119786

Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide.

PubMed

Del Angel-Meza, A R; Dávalos-Marín, A J; Ontiveros-Martinez, L L; Ortiz, G G; Beas-Zarate, C; Chaparro-Huerta, V; Torres-Mendoza, B M; Bitzer-Quintero, O K

2011-06-01

Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome

PubMed Central

SOGUT, IBRAHIM; OGLAKCI, AYSEGUL; KARTKAYA, KAZIM; OL, KEVSER KUSAT; SOGUT, MELIS SAVASAN; KANBAK, GUNGOR; INAL, MINE ERDEN

2015-01-01

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (P<0.05), the MDA level in the alcohol + boric acid group was shown to be significantly decreased compared with that in the alcohol group (P<0.01). The CAT activity of the alcohol + boric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure. PMID:25667671

Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome.

PubMed

Sogut, Ibrahim; Oglakci, Aysegul; Kartkaya, Kazim; Ol, Kevser Kusat; Sogut, Melis Savasan; Kanbak, Gungor; Inal, Mine Erden

2015-03-01

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (P<0.05), the MDA level in the alcohol + boric acid group was shown to be significantly decreased compared with that in the alcohol group (P<0.01). The CAT activity of the alcohol + boric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure.

Distribution of vesicular glutamate transporters in the human brain

PubMed Central

Vigneault, Érika; Poirel, Odile; Riad, Mustapha; Prud'homme, Josée; Dumas, Sylvie; Turecki, Gustavo; Fasano, Caroline; Mechawar, Naguib; El Mestikawy, Salah

2015-01-01

Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3) are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe) while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains. PMID:25798091

Distribution of vesicular glutamate transporters in the human brain.

PubMed

Vigneault, Érika; Poirel, Odile; Riad, Mustapha; Prud'homme, Josée; Dumas, Sylvie; Turecki, Gustavo; Fasano, Caroline; Mechawar, Naguib; El Mestikawy, Salah

2015-01-01

Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3) are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe) while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

The search of "canonical" explanations for the cerebral cortex.

PubMed

Plebe, Alessio

2018-06-15

This paper addresses a fundamental line of research in neuroscience: the identification of a putative neural processing core of the cerebral cortex, often claimed to be "canonical". This "canonical" core would be shared by the entire cortex, and would explain why it is so powerful and diversified in tasks and functions, yet so uniform in architecture. The purpose of this paper is to analyze the search for canonical explanations over the past 40 years, discussing the theoretical frameworks informing this research. It will highlight a bias that, in my opinion, has limited the success of this research project, that of overlooking the dimension of cortical development. The earliest explanation of the cerebral cortex as canonical was attempted by David Marr, deriving putative cortical circuits from general mathematical laws, loosely following a deductive-nomological account. Although Marr's theory turned out to be incorrect, one of its merits was to have put the issue of cortical circuit development at the top of his agenda. This aspect has been largely neglected in much of the research on canonical models that has followed. Models proposed in the 1980s were conceived as mechanistic. They identified a small number of components that interacted as a basic circuit, with each component defined as a function. More recent models have been presented as idealized canonical computations, distinct from mechanistic explanations, due to the lack of identifiable cortical components. Currently, the entire enterprise of coming up with a single canonical explanation has been criticized as being misguided, and the premise of the uniformity of the cortex has been strongly challenged. This debate is analyzed here. The legacy of the canonical circuit concept is reflected in both positive and negative ways in recent large-scale brain projects, such as the Human Brain Project. One positive aspect is that these projects might achieve the aim of producing detailed simulations of cortical electrical activity, a negative one regards whether they will be able to find ways of simulating how circuits actually develop.

Effect of chronic treatment with conventional and organic purple grape juices (Vitis labrusca) on rats fed with high-fat diet.

PubMed

Cardozo, Marcia Gilceane; Medeiros, Niara; Lacerda, Denise dos Santos; de Almeida, Daniela Campos; Henriques, João Antônio Pegas; Dani, Caroline; Funchal, Cláudia

2013-11-01

Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage.

Uptake of (/sup 14/C)deoxyglucose into brain of young rats with inherited hydrocephalus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richards, H.K.; Bucknall, R.M.; Jones, H.C.

1989-02-01

The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of (14C)deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain (14C) concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous atmore » 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of (14C) was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days.« less

The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study.

PubMed

Mascalchi, Mario; Ginestroni, Andrea; Toschi, Nicola; Poggesi, Anna; Cecchi, Paolo; Salvadori, Emilia; Tessa, Carlo; Cosottini, Mirco; De Stefano, Nicola; Pracucci, Giovanni; Pantoni, Leonardo; Inzitari, Domenico; Diciotti, Stefano

2014-03-01

The term leuko-araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate-to-severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate-to-severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA. Copyright © 2012 Wiley Periodicals, Inc.

Metabolic Response of the Cerebral Cortex Following Gentle Sleep Deprivation and Modafinil Administration

PubMed Central

Petit, Jean-Marie; Tobler, Irene; Kopp, Caroline; Morgenthaler, Florence; Borbély, Alexander A.; Magistretti, Pierre J.

2010-01-01

Study Objectives: The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness, followed (or not) by 3 hours of sleep recovery, on the expression of genes related to brain energy metabolism. Design: Sleep deprivation for 6–7 hours. Setting: Animal sleep research laboratory. Participants: Adults OF1 mice. Interventions: Wakefulness was maintained by “gentle sleep deprivation” method (GSD) or by administration of the wakefulness-promoting drug modafinil (MOD) (200 mg/kg i.p.). Measurements and Results: Levels of mRNAs encoding proteins related to energy metabolism were measured by quantitative real-time PCR in the cerebral cortex. The mRNAs encoding protein targeting to glycogen (PTG) and the glial glucose transporter were significantly increased following both procedures used to prolong wakefulness. Glycogenin mRNA levels were increased only after GSD, while neuronal glucose transporter mRNA only after MOD. These effects were reversed after sleep recovery. A significant enhancement of glycogen synthase activity without any changes in glycogen levels was observed in both conditions. Conclusions: These results indicate the existence of a metabolic adaptation of astrocytes aimed at maintaining brain energy homeostasis during the sleep-wake cycle. Citation: Petit, JM; Tobler I; Kopp C; Morgenthaler F; Borbély AA; Magistretti PJ. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration. SLEEP 2010;33(7):901–908. PMID:20614850

Apoptotic signaling pathways induced by acute administration of branched-chain amino acids in an animal model of maple syrup urine disease.

PubMed

Vilela, Thais C; Scaini, Giselli; Furlanetto, Camila B; Pasquali, Matheus A B; Santos, João Paulo A; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

2017-02-01

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. The affected patients present severe neurological symptoms, such as coma and seizures, as well as edema and cerebral atrophy. Considering that the mechanisms of the neurological symptoms presented by MSUD patients are still poorly understood, in this study, protein levels of apoptotic factors are measured, such as Bcl-2, Bcl-xL, Bax, caspase-3 and -8 in hippocampus and cerebral cortex of rats submitted to acute administration of branched-chain amino acids during their development. The results in this study demonstrated that BCAA acute exposure during the early postnatal period did not significantly change Bcl-2, Bcl-xL, Bax and caspase-8 protein levels. However, the Bax/Bcl-2 ratio and procaspase-3 protein levels were decreased in hippocampus. On the other hand, acute administration of BCAA in 30-day-old rats increase in Bax/Bcl-2 ratio followed by an increased caspase-3 activity in cerebral cortex, whereas BCAA induces apoptosis in hippocampus through activation and cleavage of caspase-3 and -8 without changing the Bax/Bcl-2 ratio. In conclusion, the results suggest that apoptosis could be of pivotal importance in the developmental neurotoxic effects of BCAA. In addition, the current studies also suggest that multiple mechanisms may be involved in BCAA-induced apoptosis in the cerebral cortex and hippocampus.

A comparison of the apoptotic effect of Delta(9)-tetrahydrocannabinol in the neonatal and adult rat cerebral cortex.

PubMed

Downer, Eric J; Gowran, Aoife; Campbell, Veronica A

2007-10-17

The maternal use of cannabis during pregnancy results in a number of cognitive deficits in the offspring that persist into adulthood. The endocannabinoid system has a role to play in neurodevelopmental processes such as neurogenesis, migration and synaptogenesis. However, exposure to phytocannabinoids, such as Delta(9)-tetrahydrocannabinol, during gestation may interfere with these events to cause abnormal patterns of neuronal wiring and subsequent cognitive impairments. Aberrant cell death evoked by Delta(9)-tetrahydrocannabinol may also contribute to cognitive deficits and in cultured neurones Delta(9)-tetrahydrocannabinol induces apoptosis via the CB(1) cannabinoid receptor. In this study we report that Delta(9)-tetrahydrocannabinol (5-50 microM) activates the stress-activated protein kinase, c-jun N-terminal kinase, and the pro-apoptotic protease, caspase-3, in in vitro cerebral cortical slices obtained from the neonatal rat brain. The proclivity of Delta(9)-tetrahydrocannabinol to impact on these pro-apoptotic signalling molecules was not observed in in vitro cortical slices obtained from the adult rat brain. In vivo, subcutaneous administration of Delta(9)-tetrahydrocannabinol (1-30 mg/kg) activated c-jun N-terminal kinase, caspase-3 and cathepsin-D, and induced DNA fragmentation in the cerebral cortex of neonatal rats. In contrast, in vivo administration of Delta(9)-tetrahydrocannabinol to adult rats was not associated with the apoptotic pathway in the cerebral cortex. The data provide evidence which supports the hypothesis that the neonatal rat brain is more vulnerable to the neurotoxic influence of Delta(9)-tetrahydrocannabinol, suggesting that the cognitive deficits that are observed in humans exposed to marijuana during gestation may be due, in part, to abnormal engagement of the apoptotic cascade during brain development.

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.

PubMed

Le Heron, Campbell J; Wright, Sarah L; Melzer, Tracy R; Myall, Daniel J; MacAskill, Michael R; Livingston, Leslie; Keenan, Ross J; Watts, Richard; Dalrymple-Alford, John C; Anderson, Tim J

2014-06-01

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

Functional specializations in human cerebral cortex analyzed using the Visible Man surface-based atlas

NASA Technical Reports Server (NTRS)

Drury, H. A.; Van Essen, D. C.

1997-01-01

We used surface-based representations to analyze functional specializations in the human cerebral cortex. A computerized reconstruction of the cortical surface of the Visible Man digital atlas was generated and transformed to the Talairach coordinate system. This surface was also flattened and used to establish a surface-based coordinate system that respects the topology of the cortical sheet. The linkage between two-dimensional and three-dimensional representations allows the locations of published neuroimaging activation foci to be stereotaxically projected onto the Visible Man cortical flat map. An analysis of two activation studies related to the hearing and reading of music and of words illustrates how this approach permits the systematic estimation of the degree of functional segregation and of potential functional overlap for different aspects of sensory processing.

An Integrated Software Suite for Surface-based Analyses of Cerebral Cortex

PubMed Central

Van Essen, David C.; Drury, Heather A.; Dickson, James; Harwell, John; Hanlon, Donna; Anderson, Charles H.

2001-01-01

The authors describe and illustrate an integrated trio of software programs for carrying out surface-based analyses of cerebral cortex. The first component of this trio, SureFit (Surface Reconstruction by Filtering and Intensity Transformations), is used primarily for cortical segmentation, volume visualization, surface generation, and the mapping of functional neuroimaging data onto surfaces. The second component, Caret (Computerized Anatomical Reconstruction and Editing Tool Kit), provides a wide range of surface visualization and analysis options as well as capabilities for surface flattening, surface-based deformation, and other surface manipulations. The third component, SuMS (Surface Management System), is a database and associated user interface for surface-related data. It provides for efficient insertion, searching, and extraction of surface and volume data from the database. PMID:11522765

Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.

PubMed

Pederzolli, Carolina Didonet; Mescka, Caroline Paula; Zandoná, Bernardo Remuzzi; de Moura Coelho, Daniella; Sgaravatti, Angela Malysz; Sgarbi, Mirian Bonaldi; de Souza Wyse, Angela Terezinha; Duval Wannmacher, Clóvis Milton; Wajner, Moacir; Vargas, Carmen Regla; Dutra-Filho, Carlos Severo

2010-06-01

5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.

Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under hypobaric hypoxia and the preventative effect of puerarin.

PubMed

Wang, Chi; Yan, Muyang; Jiang, Hui; Wang, Qi; He, Shang; Chen, Jingwen; Wang, Chengbin

2018-01-15

We aim to investigate the mechanism of aquaporin 4 (AQP 4) up-regulation during high-altitude cerebral edema (HACE) in rats under hypobaric hypoxia and preventative effect of puerarin. Rats were exposed to a hypobaric chamber with or without the preventative treatment of puerarin or dexamethasone. Morriz water maze was used to evaluate the spatial memory injury. HE staining and W/D ratio were used to evaluate edema injury. Rat astrocytes and microglia were co-cultured under the condition of hypoxia with the administration of p38 inhibitor, NF-κB inhibitor or puerarin. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF α) of cortex and culture supernatant were measured with ELISA. AQP4, phosphorylation of MAPKs, NF-κB pathway of cortex and astrocytes were measured by Western blot. Weakened spatial memory and cerebral edema were observed after hypobaric hypoxia exposure. AQP4, phosphorylation of NF-κB and MAPK signal pathway of cortex increased after hypoxia exposure and decreased with preventative treatment of puerarin. Hypoxia increased TNF-α and IL-6 levels in cortex and microglia and puerarin could prevent the increase of them. AQP4 of astrocytes increased after co-cultured with microglia when both were exposed to hypoxia. AQP4 showed a decrease after administered with p38 inhibitor, NF-κB inhibitor or puerarin. Hypoxia triggers inflammatory response, during which AQP4 of astrocytes can be up regulated through the release of TNF-α and IL-6 from microglia. Puerarin can exert a preventative effect on the increase of AQP4 through inhibiting the release of TNF-α and phosphorylation of NF-κB, MAPK pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress and combined exposure to low doses of pyridostigmine bromide, DEET, and permethrin produce neurochemical and neuropathological alterations in cerebral cortex, hippocampus, and cerebellum.

PubMed

Abdel-Rahman, A; Abou-Donia, Suzanne; El-Masry, Eman; Shetty, Ashok; Abou-Donia, Mohamed

2004-01-23

Exposure to a combination of stress and low doses of the chemicals pyridostigmine bromide (PB), DEET, and permethrin in adult rats, a model of Gulf War exposure, produces blood-brain barrier (BBB) disruption and neuronal cell death in the cingulate cortex, dentate gyrus, thalamus, and hypothalamus. In this study, neuropathological alterations in other areas of the brain where no apparent BBB disruption was observed was studied following such exposure. Animals exposed to both stress and chemical exhibited decreased brain acetylcholinesterase (AChE) activity in the midbrain, brainstem, and cerebellum and decreased m2 muscarinic acetylcholine (ACh) receptor ligand binding in the midbrain and cerebellum. These alterations were associated with significant neuronal cell death, reduced microtubule-associated protein (MAP-2) expression, and increased glial fibrillary acidic protein (GFAP) expression in the cerebral cortex and the hippocampal subfields CA1 and CA3. In the cerebellum, the neurochemical alterations were associated with Purkinje cell loss and increased GFAP immunoreactivity in the white matter. However, animals subjected to either stress or chemicals alone did not show any of these changes in comparison to vehicle-treated controls. Collectively, these results suggest that prolonged exposure to a combination of stress and the chemicals PB, DEET, and permethrin can produce significant damage to the cerebral cortex, hippocampus, and cerebellum, even in the absence of apparent BBB damage. As these areas of the brain are respectively important for the maintenance of motor and sensory functions, learning and memory, and gait and coordination of movements, such alterations could lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction.

Converging PET and fMRI evidence for a common area involved in human focal epilepsies

PubMed Central

Laufs, H.; Richardson, M.P.; Salek-Haddadi, A.; Vollmar, C.; Duncan, J.S.; Gale, K.; Lemieux, L.; Löscher, W.

2011-01-01

Objectives: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known. Methods: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [11C]flumazenil PET (n = 18). Results: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABAA receptor binding in the same area was reduced in patients with more frequent seizures. Conclusions: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery. PMID:21849655

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

PubMed

Wolf, Robert Christian; Walter, Henrik; Vasic, Nenad

2010-01-01

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

Adult Visual Cortical Plasticity

PubMed Central

Gilbert, Charles D.; Li, Wu

2012-01-01

The visual cortex has the capacity for experience dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate level vision - contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex. PMID:22841310

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

PubMed Central

Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

2017-01-01

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system.

PubMed

Ziel, R; Krupp, P

1976-11-15

The biotransformation of arachidonic acid to prostaglandins in vitro is specifically augmented by endogenous pyrogen to a degree depending on the concentration applied, providing that the microsomal fraction of the cerebral cortex is used as prostaglandin-synthetase system. This effect is inhibited by non-steroidal anti-inflammatory agents. These findings are compatible with the hypothesis that prostaglandins might act as mediators of the febrile reaction induced by endogenous pyrogen.

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

PubMed

Massé, Ian O; Guillemette, Sonia; Laramée, Marie-Eve; Bronchti, Gilles; Boire, Denis

2014-11-07

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks. Copyright © 2014 Elsevier B.V. All rights reserved.

Ketosis proportionately spares glucose utilization in brain.

PubMed

Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

2013-08-01

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

Increased GABA-A receptor binding and reduced connectivity at the motor cortex in children with hemiplegic cerebral palsy: a multimodal investigation using 18F-fluoroflumazenil PET, immunohistochemistry, and MR imaging.

PubMed

Park, Hae-Jeong; Kim, Chul Hoon; Park, Eun Sook; Park, Bumhee; Oh, So Ra; Oh, Maeng-Keun; Park, Chang Il; Lee, Jong Doo

2013-08-01

γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

The fate of glucose during the period of decreased metabolism after fluid percussion injury: a 13C NMR study.

PubMed

Bartnik, Brenda L; Lee, Stefan M; Hovda, David A; Sutton, Richard L

2007-07-01

The present study determined the metabolic fate of [1, 2 13C2] glucose in male control rats and in rats with moderate lateral fluid percussion injured (FPI) at 3.5 h and 24 h post-surgery. After a 3-h infusion, the amount of 13C-labeled glucose increased bilaterally (26% in left/injured cerebral cortex and 45% in right cerebral cortex) at 3.5 h after FPI and in injured cortex (45%) at 24 h after injury, indicating an accumulation of unmetabolised glucose not seen in controls. No evidence of an increase in anaerobic glycolysis above control levels was found after FPI, as 13C-labeled lactate tended to decrease at both time points and was significantly reduced (33%) in the injured cortex at 24 h post-FPI. A bilateral decrease in the 13C-labeling of both glutamate and glutamine was observed in the FPI rats at 3.5 h and the glutamine pool remained significantly decreased in the injured cortex at 24 h, suggesting reduced oxidative metabolism in both neuronal and astrocyte compartments after injury. The percentage of glucose metabolism through the pentose phosphate pathway (PPP) increased in the injured (13%) and contralateral (11%) cortex at 3.5 h post-FPI and in the injured cortex (9%) at 24 h post-injury. Based upon the changes in metabolite pools, our results show an injury-induced decrease in glucose utilization and oxidation within the first 24 h after FPI. Increased metabolism through the PPP would result in increased NADPH synthesis, suggesting a need for reducing equivalents after FPI to help restore the intracellular redox state and/or in response to free radical stress.

Intraocular pressure and cerebral oxygenation during prolonged headward acceleration.

PubMed

Eiken, Ola; Keramidas, Michail E; Taylor, Nigel A S; Grönkvist, Mikael

2017-01-01

Supra-tolerance head-to-foot directed gravitoinertial load (+Gz) typically induces a sequence of symptoms/signs, including loss of: peripheral vision-central vision-consciousness. The risk of unconsciousness is greater when anti-G-garment failure occurs after prolonged rather than brief exposures, presumably because, in the former condition, mental signs are not consistently preceded by impaired vision. The aims were to investigate if prolonged exposure to moderately elevated +Gz reduces intraocular pressure (IOP; i.e., improves provisions for retinal perfusion), or the cerebral anoxia reserve. Subjects were exposed to 4-min +Gz plateaux either at 2 and 3 G (n = 10), or at 4 and 5 G (n = 12). Measurements included eye-level mean arterial pressure (MAP), oxygenation of the cerebral frontal cortex, and at 2 and 3 G, IOP. IOP was similar at 1 (14.1 ± 1.6 mmHg), 2 (14.0 ± 1.6 mmHg), and 3 G (14.0 ± 1.6 mmHg). During the G exposures, MAP exhibited an initial prompt drop followed by a partial recovery, end-exposure values being reduced by ≤30 mmHg. Cerebral oxygenation showed a similar initial drop, but without recovery, and was followed by either a plateau or a further slight decrement to a minimum of about -14 μM. Gz loading did not affect IOP. That cerebral oxygenation remained suppressed throughout these G exposures, despite a concomitant partial recovery of MAP, suggests that the increased risk of unconsciousness upon G-garment failure after prolonged +Gz exposure is due to reduced cerebral anoxia reserve.

Female exposure to high G: effects of simulated combat sorties on cerebral and arterial O2 saturation.

PubMed

Tripp, L D; Chelette, T; Savul, S; Widman, R A

1998-09-01

One of the key factors in maintaining optimal cognitive performance in the high-G environment is the adequate delivery of oxygen to the cerebral tissue. As eye-level blood pressure is compromised at 22 mmHg x G(-1), perfusion to the peripheral cerebral tissues (cerebral cortex) may not be adequate to support the mental demands of flight. This study measured the effect of closed-loop flight simulations (3 min) on cerebral oxygen saturation changes (rSO2), arterial oxygen saturation (SAO2), and heart rate (HR), in both rested (8 h of rest) and sleepless (24 h without sleep) conditions. Subjects (16; 8 males and 8 females) were subjected to G-exposures via closed-loop flight simulations in a series of four 3-min sorties flown by subjects on the Dynamic Environment Simulator (centrifuge) in either a rested or a sleepless state. Prior to the centrifuge flight, subjects were instrumented with sensors for measurement of arterial oxygen saturation (SAO2) and regional cerebral tissue oxygenation (rSO2). Subjects wore the standard flight suit, boots, CSU-13B/P anti-G suit, and the COMBAT EDGE positive-pressure breathing for G-protection system. Significant changes in cerebral and arterial oxygen saturation were observed within groups when comparing pretest baselines and minimum values during the test and pre- and post-G rSO2, SAO2, and HR in both the rested and sleepless state, (p # 0.01), respectively, for each group. Comparisons between groups showed women to have significantly smaller regional cerebral cortex oxygen decreases than men (p # 0.01). No significant changes in SAO2, however, were observed between groups. Both men and women showed a slow recovery of rSO2 values to the prebaseline levels. Sleeplessness had no effect on the rSO2, SAO2, and HR compared with the rested condition. During acceleration, regional cerebral tissue oxygen decreased 13% in men compared with 9% in women. The recovery of cerebral tissue oxygen levels to prebaseline values was retarded somewhat when compared with the recovery response of arterial oxygen saturation.

Transcranial direct current stimulation over prefrontal cortex diminishes degree of risk aversion.

PubMed

Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Jia, Yongmin; Luo, Jun

2015-06-26

Previous studies have established that transcranial direct current stimulation (tDCS) is a powerful technique for manipulating the activity of the human cerebral cortex. Many studies have found that weighing the risks and benefits in decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). We studied whether participants change the balance of risky and safe responses after receiving tDCS applied over the right and left prefrontal cortex. A total of 60 healthy volunteers performed a risk task while they received either anodal tDCS over the right prefrontal cortex, with cathodal over the left; anodal tDCS over the left prefrontal cortex, with cathodal over the right; or sham stimulation. The participants tended to choose less risky options after receiving sham stimulation, demonstrating that the task might be highly influenced by the "wealth effect". There was no statistically significant change after either right anodal/left cathodal or left anodal/right cathodal tDCS, indicating that both types of tDCS impact the participants' degrees of risk aversion, and therefore, counteract the wealth effect. We also found gender differences in the participants' choices. These findings extend the notion that DLPFC activity is critical for risk decision-making. Application of tDCS to the right/left DLPFC may impact a person's attitude to taking risks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dugway Proving Ground: Closure Plan Module 2, for SWMUs 20, 164, 166 and 170

DTIC Science & Technology

1997-07-01

Lewin and J.H. Holmes, 1972. Syndrome of Dyspraxia and Multifocal Seizure Associated with Chronic Hemodialysis. Trans. Am. Soc. Artif. Intern. Organs. 18...Many cases of nasal mucosal injury (inflamed mucosa, ulcerated or perforated septum) in workers exposed to Cr0 3 have been reported (Bloomfield and...mg/kg chromium for 3 or 6 weeks. These changes included neuronal degeneration in the cerebral cortex, marked O DUG\\0566 07/11/96 4:19pm bpw B.3-69

Embedding Task-Based Neural Models into a Connectome-Based Model of the Cerebral Cortex

PubMed Central

Ulloa, Antonio; Horwitz, Barry

2016-01-01

A number of recent efforts have used large-scale, biologically realistic, neural models to help understand the neural basis for the patterns of activity observed in both resting state and task-related functional neural imaging data. An example of the former is The Virtual Brain (TVB) software platform, which allows one to apply large-scale neural modeling in a whole brain framework. TVB provides a set of structural connectomes of the human cerebral cortex, a collection of neural processing units for each connectome node, and various forward models that can convert simulated neural activity into a variety of functional brain imaging signals. In this paper, we demonstrate how to embed a previously or newly constructed task-based large-scale neural model into the TVB platform. We tested our method on a previously constructed large-scale neural model (LSNM) of visual object processing that consisted of interconnected neural populations that represent, primary and secondary visual, inferotemporal, and prefrontal cortex. Some neural elements in the original model were “non-task-specific” (NS) neurons that served as noise generators to “task-specific” neurons that processed shapes during a delayed match-to-sample (DMS) task. We replaced the NS neurons with an anatomical TVB connectome model of the cerebral cortex comprising 998 regions of interest interconnected by white matter fiber tract weights. We embedded our LSNM of visual object processing into corresponding nodes within the TVB connectome. Reciprocal connections between TVB nodes and our task-based modules were included in this framework. We ran visual object processing simulations and showed that the TVB simulator successfully replaced the noise generation originally provided by NS neurons; i.e., the DMS tasks performed with the hybrid LSNM/TVB simulator generated equivalent neural and fMRI activity to that of the original task-based models. Additionally, we found partial agreement between the functional connectivities using the hybrid LSNM/TVB model and the original LSNM. Our framework thus presents a way to embed task-based neural models into the TVB platform, enabling a better comparison between empirical and computational data, which in turn can lead to a better understanding of how interacting neural populations give rise to human cognitive behaviors. PMID:27536235

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

PubMed Central

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Opiate receptors in idiopathic generalised epilepsy measured with [11C]diprenorphine and positron emission tomography.

PubMed

Prevett, M C; Cunningham, V J; Brooks, D J; Fish, D R; Duncan, J S

1994-09-01

The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.

Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease.

PubMed

de Haas, Ria; Das, Devashish; Garanto, Alejandro; Renkema, Herma G; Greupink, Rick; van den Broek, Petra; Pertijs, Jeanne; Collin, Rob W J; Willems, Peter; Beyrath, Julien; Heerschap, Arend; Russel, Frans G; Smeitink, Jan A

2017-09-15

Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 -/- mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 -/- mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 -/- mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 -/- mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing.

Effect of 3,5,3'-triiodothyronine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolic responses.

PubMed

Chopra, I J; Huang, T S; Hurd, R E; Solomon, D H

1984-04-01

We studied the effect of T3-induced hyperthyroidism on the outer ring (5' or 3') monodeiodination of T4 (to T3) and 3',5'-diiodothyronine [3',5'-T2; to 3'-monoiodothyronine (3'-T1)] and on the inner ring (3 or 5) monodeiodination of 3,5-T2 (to 3-T1) by various rat tissues. Weight-matched pairs of male Sprague-Dawley rats were given either saline or T3 (20 micrograms/100 g BW daily) ip for 3 days. The metabolism of the iodothyronines was studied on day 4 in homogenates of the tissues in the presence of 25 mM dithiothreitol. Hyperthyroidism was associated with a significant (P less than 0.05) increase in T4 to T3 monodeiodinating activity in the liver (mean, 95%), kidney (mean, 60%), and heart (mean, 153%), but not in skeletal muscle, small intestine, spleen, testis, cerebral cortex, or cerebellum. The monodeiodinating activity converting 3',5'-T2 to 3'-T1 was greatly increased (P less than 0.05) in the heart (mean, 750%), spleen (mean, 462%), and skeletal muscle (mean, 167%), but not in liver, kidney, small intestine, testis, cerebral cortex, or cerebellum. In the case of liver and kidney, however, there was evidence of an activation of 3',5'-T2 monodeiodinating activity, as suggested by a significant increase in the activity in the absence of added dithiothreitol. The monodeiodination of 3,5-T2 to 3-T1 increased significantly only in the cerebral cortex (mean, 525%) and liver (mean, 69%) and not in any other tissue. The time course of the above-mentioned changes in iodothyronine metabolism was studied in groups of rats (five per group) given T3 (20 micrograms 100 g BW-1 day-1) 6-72 h before death. Significant increases in 3',5'-T2 (to 3'-T1) monodeiodination in the heart and 3,5-T2 (to 3-T1) monodeiodination in the cerebral cortex were evident within 6 h of T3 administration. Changes in T4 to T3 monodeiodinating activity in the kidney and liver, however, did not become statistically significant until 24 and 72 h, respectively. The various effects of T3 on the tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Intraoperative application of thermal camera for the assessment of during surgical resection or biopsy of human's brain tumors

NASA Astrophysics Data System (ADS)

Kastek, M.; Piatkowski, T.; Polakowski, H.; Kaczmarska, K.; Czernicki, Z.; Bogucki, J.; Zebala, M.

2014-05-01

Motivation to undertake research on brain surface temperature in clinical practice is based on a strong conviction that the enormous progress in thermal imaging techniques and camera design has a great application potential. Intraoperative imaging of pathological changes and functionally important areas of the brain is not yet fully resolved in neurosurgery and remains a challenge. A study of temperature changes across cerebral cortex was performed for five patients with brain tumors (previously diagnosed using magnetic resonance or computed tomography) during surgical resection or biopsy of tumors. Taking into account their origin and histology the tumors can be divided into the following types: gliomas, with different degrees of malignancy (G2 to G4), with different metabolic activity and various temperatures depending on the malignancy level (3 patients), hypervascular tumor associated with meninges (meningioma), metastatic tumor - lung cancer with a large cyst and noticeable edema. In the case of metastatic tumor with large edema and a liquid-filled space different temperature of a cerebral cortex were recorded depending on metabolic activity. Measurements have shown that the temperature on the surface of the cyst was on average 2.6 K below the temperature of surrounding areas. It has been also observed that during devascularization of a tumor, i.e. cutting off its blood vessels, the tumor temperature lowers significantly in spite of using bipolar coagulation, which causes additional heat emission in the tissue. The results of the measurements taken intra-operatively confirm the capability of a thermal camera to perform noninvasive temperature monitoring of a cerebral cortex. As expected surface temperature of tumors is different from surface temperature of tissues free from pathological changes. The magnitude of this difference depends on histology and the origin of the tumor. These conclusions lead to taking on further experimental research, implementation and further verification of the thermal imaging method and its usefulness in clinical practice. In particular the research will be undertaken on intraoperative temperature changes of active cerebral cortex areas in post-anesthetic recovery.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice.

PubMed

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-03-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice

PubMed Central

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-01-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex. PMID:29257130

Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI.

PubMed

Lerch, Jason P; Worsley, Keith; Shaw, W Philip; Greenstein, Deanna K; Lenroot, Rhoshel K; Giedd, Jay; Evans, Alan C

2006-07-01

We introduce MACACC-Mapping Anatomical Correlations Across Cerebral Cortex-to study correlated changes within and across different cortical networks. The principal topic of investigation is whether the thickness of one area of the cortex changes in a statistically correlated fashion with changes in thickness of other cortical regions. We further extend these methods by introducing techniques to test whether different population groupings exhibit significantly varying MACACC patterns. The methods are described in detail and applied to a normal childhood development population (n = 292), and show that association cortices have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed region revealed MACACC patterns strikingly similar to tractography maps obtained from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with age, older subjects featuring tighter correlations with BA 44 in the anterior portions of the superior temporal gyri. Lastly, IQ-dependent MACACC differences were investigated, revealing steeper correlations between BA 44 and multiple frontal and parietal regions for the higher IQ group, most significantly (t = 4.0) in the anterior cingulate.

Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions

PubMed Central

Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; Robles, Victor; Yuste, Rafael; DeFelipe, Javier

2013-01-01

Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms. PMID:22710613

Label-free imaging of cortical structures with multiphoton microscopy

NASA Astrophysics Data System (ADS)

Wang, Shu; Chen, Xiuqiang; Wu, Weilin; Chen, Zhida; Lin, Ruolan; Lin, Peihua; Wang, Xingfu; Fu, Yu Vincent; Chen, Jianxin

2017-02-01

Cortical structures in the central nervous system exhibit an ordered laminar organization. Defined cell layers are significant to our understanding of brain structure and function. In this work, multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), which was applied for qualitatively visualizing the structure of cerebral and cerebellar cortex from the fresh, unfixed, and unstained specimen. MPM is able to effectively identify neurons and neurites in cerebral cortex, as well as glial cells, Purkinje cells, and granule cells in cerebellar cortex at subcellular resolution. In addition, the use of automated image processing algorithms can quantify the circularity of neurons and the density distribution of neurites based on the intrinsic nonlinear optical contrast, further providing quantitative characteristics for automatically analyzing the laminar structure of cortical structures. These results suggest that with the development of the feasibility of two-photon fiberscopes and microendoscope probes, the combined MPM and image analysis holds potential to provide supplementary information to augment the diagnostic accuracy of neuropathology and in vivo identification of various neurological illnesses in clinic.

Foxp1 Regulates Cortical Radial Migration and Neuronal Morphogenesis in Developing Cerebral Cortex

PubMed Central

Li, Xue; Xiao, Jian; Fröhlich, Henning; Tu, Xiaomeng; Li, Lianlian; Xu, Yue; Cao, Huateng; Qu, Jia; Rappold, Gudrun A.; Chen, Jie-Guang

2015-01-01

FOXP1 is a member of FOXP subfamily transcription factors. Mutations in FOXP1 gene have been found in various development-related cognitive disorders. However, little is known about the etiology of these symptoms, and specifically the function of FOXP1 in neuronal development. Here, we report that suppression of Foxp1 expression in mouse cerebral cortex led to a neuronal migration defect, which was rescued by overexpression of Foxp1. Mice with Foxp1 knockdown exhibited ectopic neurons in deep layers of the cortex postnatally. The neuronal differentiation of Foxp1-downregulated cells was normal. However, morphological analysis showed that the neurons with Foxp1 deficiency had an inhibited axonal growth in vitro and a weakened transition from multipolar to bipolar in vivo. Moreover, we found that the expression of Foxp1 modulated the dendritic maturation of neurons at a late postnatal date. Our results demonstrate critical roles of Foxp1 in the radial migration and morphogenesis of cortical neurons during development. This study may shed light on the complex relationship between neuronal development and the related cognitive disorders. PMID:26010426

Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (/sup 18/F)fluorodeoxyglucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedland, R.P.; Budinger, T.F.; Ganz, E.

1983-08-01

Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using (/sup 18/F)fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in allmore » the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.« less

Brain correlates of stuttering and syllable production. A PET performance-correlation analysis.

PubMed

Fox, P T; Ingham, R J; Ingham, J C; Zamarripa, F; Xiong, J H; Lancaster, J L

2000-10-01

To distinguish the neural systems of normal speech from those of stuttering, PET images of brain blood flow were probed (correlated voxel-wise) with per-trial speech-behaviour scores obtained during PET imaging. Two cohorts were studied: 10 right-handed men who stuttered and 10 right-handed, age- and sex-matched non-stuttering controls. Ninety PET blood flow images were obtained in each cohort (nine per subject as three trials of each of three conditions) from which r-value statistical parametric images (SPI¿r¿) were computed. Brain correlates of stutter rate and syllable rate showed striking differences in both laterality and sign (i.e. positive or negative correlations). Stutter-rate correlates, both positive and negative, were strongly lateralized to the right cerebral and left cerebellar hemispheres. Syllable correlates in both cohorts were bilateral, with a bias towards the left cerebral and right cerebellar hemispheres, in keeping with the left-cerebral dominance for language and motor skills typical of right-handed subjects. For both stutters and syllables, the brain regions that were correlated positively were those of speech production: the mouth representation in the primary motor cortex; the supplementary motor area; the inferior lateral premotor cortex (Broca's area); the anterior insula; and the cerebellum. The principal difference between syllable-rate and stutter-rate positive correlates was hemispheric laterality. A notable exception to this rule was that cerebellar positive correlates for syllable rate were far more extensive in the stuttering cohort than in the control cohort, which suggests a specific role for the cerebellum in enabling fluent utterances in persons who stutter. Stutters were negatively correlated with right-cerebral regions (superior and middle temporal gyrus) associated with auditory perception and processing, regions which were positively correlated with syllables in both the stuttering and control cohorts. These findings support long-held theories that the brain correlates of stuttering are the speech-motor regions of the non-dominant (right) cerebral hemisphere, and extend this theory to include the non-dominant (left) cerebellar hemisphere. The present findings also indicate a specific role of the cerebellum in the fluent utterances of persons who stutter. Support is also offered for theories that implicate auditory processing problems in stuttering.

Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

PubMed

Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

2005-12-15

We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

Homolateral ataxia and crural paresis: a crossed cerebral-cerebellar diaschisis.

PubMed Central

Giroud, M; Creisson, E; Fayolle, H; Gras, P; Vion, P; Brunotte, F; Dumas, R

1994-01-01

A patient developed weakness of the right leg and homolateral ataxia of the arm, caused by a subcortical infarct in the area supplied by the anterior cerebral artery in the left paracentral region, demonstrated by CT and MRI. Cerebral blood flow studied by technetium-labelled hexamethyl-propylene-amine oxime using single photon emission computed tomography showed decreased blood flow in the left lateral frontal cortex and in the right cerebellar hemisphere ("crossed cerebral-cerebellar diaschisis"). The homolateral ataxia of the arm may be caused by decreased function of the right cerebellar hemisphere, because of a lesion of the corticopontine-cerebellar tracts, whereas crural hemiparesis is caused by a lesion of the upper part of the corona radiata. Images PMID:8126511

The theory of an agnosic right shift gene in schizophrenia and autism.

PubMed

Annett, M

1999-10-19

The right shift (RS) theory (Annett, M., 1972. The distribution of manual asymmetry. Br. J. Psychol. 63, 343-358; Annett, M., 1985. Left, Right, Hand and Brain: The Right Shift Theory. Lawrence Erlbaum, London) suggests that the typical pattern of human cerebral and manual asymmetries depends on a single gene (RS+) which impairs speech-related cortex of the right hemisphere. The theory offers solutions to several puzzles, including the distribution of handedness in families (Annett, M., 1978. A Single Gene Explanation of Right and Left Handedness and Brainedness. Lanchester Polytechnic, Coventry; Annett, M., 1996. In defense of the right shift theory. Percept. Motor Skills 82, 115-137), relations between handedness and cerebral speech laterality (Annett, M., 1975. Hand preference and the laterality of cerebral speech. Cortex 11, 305-328; Annett, M., Alexander, M.P., 1996. Atypical cerebral dominance: predictions and tests of the right shift theory. Neuropsychologia 34, 1215-1227) and handedness and dyslexia (Annett, M. et al., 1996. Types of dyslexia and the shift to dextrality. J. Child Psychol. Psychiatry 37, 167-180). If Crow's (Crow, T.J. et al., 1989. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch. Gen. Psychiatry 46, 1145-1150; Crow, T.J., 1997. Is schizophrenia the price that Homo sapiens pays for language? Schizophr. Res. 28, 127-141) theory that schizophrenia is due to an anomaly of cerebral dominance is correct, and if the RS theory is correct, schizophrenia could be due to an anomaly of the RS+ gene. If the RS+ gene were at risk for a mutation which caused a loss of directional coding, the mutant could be described as 'agnosic' for left and right. Such a gene would impair either hemisphere at random. When paired with another RS+ gene, both hemispheres would be impaired in 50% of cases. The other 50% and people in whom the agnosic gene is paired with an RS-allele (neutral for asymmetry and not giving hemisphere impairment) would have one unaffected hemisphere and, thus, normal development. Quantitative predictions based on the RS genetic theory as previously developed, plus an agnosic mutant with frequency required to give schizophrenia in 1% of the population, are consistent with estimates of concordance for schizophrenia in relatives. Homozygotes of the agnosic mutant would occur at about the rate estimated for autism.

Effects of dexmedetomidine on microregional O2 balance during reperfusion after focal cerebral ischemia.

PubMed

Chi, Oak Z; Grayson, Jeremy; Barsoum, Sylviana; Liu, Xia; Dinani, Aliraza; Weiss, Harvey R

2015-01-01

This study was performed to determine whether there is an association between microregional O2 balance and neuronal survival in cerebral ischemia-reperfusion using dexmedetomidine, an α2-adrenoreceptor agonist and a sedative. Rats were subjected to 1 hour middle cerebral artery occlusion and a 2-hour reperfusion. During reperfusion, normal saline (n = 14) or dexmedetomidine 1 μg/kg/minute (n = 14) was infused intravenously. At 2 hours of reperfusion, regional cerebral blood flow using (14)C-iodoantipyrine autoradiography, microregional arterial and venous (20-60 μm in diameter) O2 saturation (SvO2) using cryomicrospectrophotometry, and the size of cortical infarction were determined. Ischemia-reperfusion decreased microregional SvO2 (52.9 ± 3.7% vs. 61.1 ± .6%, P < .005) with increased variation or heterogeneity (P < .0001) with similar regional cerebral blood flow and O2 consumption. Dexmedetomidine during reperfusion decreased the heterogeneity of SvO2 that was analyzed with an analysis of variance (P < .01) and reported as coefficient of variation (100 × standard deviation/Mean) (11.8 vs. 16.4). The number of veins with O2 saturation less than 50% decreased with dexmedetomidine (13/80 vs. 27/81, P < .01). The percentage of cortical infarct in total cortex was smaller with dexmedetomidine (8.3 ± 2.2% vs. 12.6 ± 1.5%, P < .005). In the cerebral ischemic reperfused cortex, dexmedetomidine decreased the heterogeneity of SvO2 and the number of small veins with low O2 saturation suggesting improved microregional O2 supply/consumption balance. The improvement was accompanied by the reduced size of cortical infarction. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization

PubMed Central

Rengifo Valbuena, Carlos Augusto; Ávila Rodríguez, Marco Fidel; Céspedes Rubio, Angel

2013-01-01

Introduction: The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemia can be used to evaluate the cellular response phenomena and possible neurological protection by drugs. Objective: To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. Methods: Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with α-bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 μL) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). Results: Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in the somato-sensory cortex and CA1 (p <0.001). Conclusions: The regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture , gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemia in the acute phase. PMID:24892319

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory

PubMed Central

Bastos, André M.; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K.

2018-01-01

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50–250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4–22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. PMID:29339471

Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder.

PubMed

Bremner, J Douglas; Vermetten, Eric; Vythilingam, Meena; Afzal, Nadeem; Schmahl, Christian; Elzinga, Bernet; Charney, Dennis S

2004-03-15

The anterior cingulate and medial prefrontal cortex play an important role in the inhibition of responses, as measured by the Stroop task, as well as in emotional regulation. Dysfunction of the anterior cingulate/medial prefrontal cortex has been implicated in posttraumatic stress disorder (PTSD). The purpose of this study was to use the Stroop task as a probe of anterior cingulate function in PTSD. Women with early childhood sexual abuse-related PTSD (n = 12) and women with abuse but without PTSD (n = 9) underwent positron emission tomographic measurement of cerebral blood flow during exposure to control, color Stroop, and emotional Stroop conditions. Women with abuse with PTSD (but not abused non-PTSD women) had a relative decrease in anterior cingulate blood flow during exposure to the emotional (but not color) classic Stroop task. During the color Stroop there were also relatively greater increases in blood flow in non-PTSD compared with PTSD women in right visual association cortex, cuneus, and right inferior parietal lobule. These findings add further evidence for dysfunction of a network of brain regions, including anterior cingulate and visual and parietal cortex, in abuse-related PTSD.

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

PubMed

Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

2018-01-30

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

Evolution and development of the mammalian cerebral cortex.

PubMed

Molnár, Zoltán; Kaas, Jon H; de Carlos, Juan A; Hevner, Robert F; Lein, Ed; Němec, Pavel

2014-01-01

Comparative developmental studies of the mammalian brain can identify key changes that can generate the diverse structures and functions of the brain. We have studied how the neocortex of early mammals became organized into functionally distinct areas, and how the current level of cortical cellular and laminar specialization arose from the simpler premammalian cortex. We demonstrate the neocortical organization in early mammals, which helps to elucidate how the large, complex human brain evolved from a long line of ancestors. The radial and tangential enlargement of the cortex was driven by changes in the patterns of cortical neurogenesis, including alterations in the proportions of distinct progenitor types. Some cortical cell populations travel to the cortex through tangential migration whereas others migrate radially. A number of recent studies have begun to characterize the chick, mouse and human and nonhuman primate cortical transcriptome to help us understand how gene expression relates to the development and anatomical and functional organization of the adult neocortex. Although all mammalian forms share the basic layout of cortical areas, the areal proportions and distributions are driven by distinct evolutionary pressures acting on sensory and motor experiences during the individual ontogenies. © 2014 S. Karger AG, Basel.

Neurophysiology and functional neuroanatomy of pain perception.

PubMed

Schnitzler, A; Ploner, M

2000-11-01

The traditional view that the cerebral cortex is not involved in pain processing has been abandoned during the past decades based on anatomic and physiologic investigations in animals, and lesion, functional neuroimaging, and neurophysiologic studies in humans. These studies have revealed an extensive central network associated with nociception that consistently includes the thalamus, the primary (SI) and secondary (SII) somatosensory cortices, the insula, and the anterior cingulate cortex (ACC). Anatomic and electrophysiologic data show that these cortical regions receive direct nociceptive thalamic input. From the results of human studies there is growing evidence that these different cortical structures contribute to different dimensions of pain experience. The SI cortex appears to be mainly involved in sensory-discriminative aspects of pain. The SII cortex seems to have an important role in recognition, learning, and memory of painful events. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in affective aspects of pain-related learning and memory. The ACC is closely related to pain unpleasantness and may subserve the integration of general affect, cognition, and response selection. The authors review the evidence on which the proposed relationship between cortical areas, pain-related neural activations, and components of pain perception is based.

A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

PubMed Central

Markov, N. T.; Ercsey-Ravasz, M. M.; Ribeiro Gomes, A. R.; Lamy, C.; Magrou, L.; Vezoli, J.; Misery, P.; Falchier, A.; Quilodran, R.; Gariel, M. A.; Sallet, J.; Gamanut, R.; Huissoud, C.; Clavagnier, S.; Giroud, P.; Sappey-Marinier, D.; Barone, P.; Dehay, C.; Toroczkai, Z.; Knoblauch, K.; Van Essen, D. C.; Kennedy, H.

2014-01-01

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks. PMID:23010748

Effects of acupuncture on tissue-oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

Wild Type Bone Marrow Transplant Partially Reverses Neuroinflammation in Progranulin-Deficient Mice

PubMed Central

Yang, Yue; Aloi, Macarena S.; Cudaback, Eiron; Josephsen, Samuel R.; Rice, Samantha J.; Jorstad, Nikolas L.; Keene, C. Dirk; Montine, Thomas J.

2014-01-01

Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases. PMID:25199051

New Information about Albert Einstein's Brain.

PubMed

Falk, Dean

2009-01-01

In order to glean information about hominin (or other) brains that no longer exist, details of external neuroanatomy that are reproduced on endocranial casts (endocasts) from fossilized braincases may be described and interpreted. Despite being, of necessity, speculative, such studies can be very informative when conducted in light of the literature on comparative neuroanatomy, paleontology, and functional imaging studies. Albert Einstein's brain no longer exists in an intact state, but there are photographs of it in various views. Applying techniques developed from paleoanthropology, previously unrecognized details of external neuroanatomy are identified on these photographs. This information should be of interest to paleoneurologists, comparative neuroanatomists, historians of science, and cognitive neuroscientists. The new identifications of cortical features should also be archived for future scholars who will have access to additional information from improved functional imaging technology. Meanwhile, to the extent possible, Einstein's cerebral cortex is investigated in light of available data about variation in human sulcal patterns. Although much of his cortical surface was unremarkable, regions in and near Einstein's primary somatosensory and motor cortices were unusual. It is possible that these atypical aspects of Einstein's cerebral cortex were related to the difficulty with which he acquired language, his preference for thinking in sensory impressions including visual images rather than words, and his early training on the violin.

Functional recovery of neuronal activity in rat whisker-barrel cortex sensory pathway from freezing injury after transplantation of adult bone marrow stromal cells.

PubMed

Mori, Kentaro; Iwata, Junko; Miyazaki, Masahiro; Nakao, Yasuaki; Maeda, Minoru

2005-07-01

The effect of transplantation of adult bone marrow stromal cells (MSCs) into the freeze-lesioned left barrel field cortex in the rat was investigated by measurement of local cerebral glucose utilization (lCMR(glc)) in the anatomic structures of the whisker-to-barrel cortex sensory pathway. Bone marrow stromal cells or phosphate-buffered saline (PBS) were injected intracerebrally into the boundary zone 1 h after induction of the freezing cortical lesion. Three weeks after surgery, the 2-[(14)C]deoxyglucose method was used to measure lCMR(glc) during right whisker stimulation. The volume of the primary necrotic freezing lesion was significantly reduced (P<0.05), and secondary retrograde degeneration in the left ventral posteromedial (VPM) thalamic nucleus was diminished in the MSC-treated group. Local cerebral glucose utilization measurements showed that the freezing cortical lesion did not alter the metabolic responses to stimulation in the brain stem trigeminal nuclei, but eliminated the responses in the left VPM nucleus and periphery of the barrel cortex in the PBS-treated group. The left/right (stimulated/unstimulated) lCMR(glc) ratios were significantly improved in both the VPM nucleus and periphery of the barrel cortex in the MSC-treated group compared with the PBS-treated group (P<0.05). These results indicate that MSC transplantation in adults may stimulate metabolic and functional recovery in injured neuronal pathways.

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

PubMed

Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-Shan R

2015-02-15

The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

A Perfusion MRI Study of Emotional Valence and Arousal in Parkinson's Disease

PubMed Central

Limsoontarakul, Sunsern; Campbell, Meghan C.; Black, Kevin J.

2011-01-01

Background. Brain regions subserving emotion have mostly been studied using functional magnetic resonance imaging (fMRI) during emotion provocation procedures in healthy participants. Objective. To identify neuroanatomical regions associated with spontaneous changes in emotional state over time. Methods. Self-rated emotional valence and arousal scores, and regional cerebral blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random-effects SPM analysis, corrected for multiple comparisons, identified significant clusters of contiguous voxels in which rCBF varied with valence or arousal. Results. Emotional valence correlated positively with rCBF in several brain regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and white matter near putamen, thalamus, insula, and medial PFC. Valence correlated negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC, and precuneus—posterior cingulate cortex (PCC). Arousal correlated positively with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior parietal lobule and correlated negatively in clusters including posterior insula—mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the temporal stability of perfusion MRI allows within-subject investigations of spontaneous fluctuations in mental state, such as mood, over relatively long-time intervals. PMID:21969917

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

PubMed

Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

2002-12-01

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Correlations Decrease with Propagation of Spiking Activity in the Mouse Barrel Cortex

PubMed Central

Ranganathan, Gayathri Nattar; Koester, Helmut Joachim

2011-01-01

Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex. PMID:21629764

Actions of certain amines on cerebral cortical neurones

PubMed Central

Krnjević, K.; Phillis, J. W.

1963-01-01

A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of γ-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action. PMID:14035890

Direct cerebral and cardiac 17O-MRI at 3 Tesla: initial results at natural abundance.

PubMed

Borowiak, Robert; Groebner, Jens; Haas, Martin; Hennig, Jürgen; Bock, Michael

2014-02-01

To establish direct (17)O-magnetic resonance imaging (MRI) for metabolic imaging at a clinical field strength of 3 T. An experimental setup including a surface coil and transmit/receive switch was constructed. Natural abundance in vivo brain images of a volunteer were acquired with a radial three-dimensional (3D) sequence in the visual cortex and in the heart with electrocardiogram (ECG)-gating. In the brain, a signal-to-noise ratio of 36 was found at a nominal resolution of (5.6 mm)(3), and a transverse relaxation time of T(2)* = (1.9 ± 0.2) ms was obtained. In the heart (17)O images were acquired with a temporal resolution of 200 ms. Cerebral and cardiac (17)O-MRI at natural abundance is feasible at 3 T.

Reversal of normal cerebral sexual dimorphism in schizophrenia: evidence and speculations.

PubMed

Mendrek, Adrianna

2007-01-01

Sex differences in epidemiology, clinical course and symptomatology of schizophrenia have been widely documented, but still relatively little is known about the brain sexual dimorphism in this psychiatric disorder. While some neuroanatomical and neuropsychological studies have reported existence of differences between male and female patients in a direction of normal sexual dimorphism, others did not find any effect. A few recent reports point to a peculiar disturbance of normal sexual dimorphism in brain regions implicated in the processing of emotions, including amygdala, orbitofrontal cortex and anterior cingulate. Prompted by these findings we compared cerebral activations between the sexes during performance of two emotion processing tasks and found overall much more extensive and intense cerebral activations in men than in women with schizophrenia. Moreover, the pattern of obtained sex differences in cerebral activation in patients differed significantly from what has been observed in the general population. Based on these preliminary structural and functional neuroimaging data, as well as some clinical reports, it is hypothesized in the present paper that schizophrenia is characterized by a reversed (or at least seriously disturbed) cerebral sexual dimorphism. It is further argued that this phenomenon stems from masculinization and/or un-feminization of females and feminizations and/or un-masculinization of males by sex steroid hormones, such as estrogen and testosterone, during both organizational and activational stages of neurodevelopment.

Effects of bioactive tetrapeptides on free-radical processes.

PubMed

Kozina, L S

2007-06-01

Injections of epithalon and cortagen to rats decreased the content of LPO products and reduced oxidative modification of proteins, which was paralleled by suppression of antioxidant activity in rat serum and cerebral cortex.

Nutrition and the Nervous System: The Historical Background

ERIC Educational Resources Information Center

Widdowson, E. M.

1972-01-01

Discusses the reciprocal relationship between food and behavior, dealing with the subject as a two-way system; two parts of the brain are particularly involved, the hypothalamus and the cerebral cortex. (Author/JM)

[Influence of toxin botulin on walk stereotype of children with juvenile cerebral palsy. The functional examination performed by BTS, comprehensive movement analysis system. A preliminary report].

PubMed

Kwiecień-Czerwieniec, Ilona; Krukowska, Jolanta; Woldańska-Okońska, Marta

2014-01-01

Juvenile Cerebral Palsy--is caused by damage of the motor control centers of the developing brain (cerebral refers to the cerebrum, which is the affected area of the brain, although the disorder probably involves connections between the cortex and other parts of the brain and palsy refers to disorder of movement). The clinical symptoms of juvenile cerebral palsy are very diversified and include gross and fine motor-coordination disorders, manual ability, locomotion, perception and response, speech, psychomotor retardation, emotional disorders. The primary therapeutic problem in children with cerebral palsy is learning to move in a lower position and learning to walk. The aim of this research is evaluation the action of the botulinum toxin on gait pattern of children with cerebral palsy. Application of a comprehensive BTS analysis of gait will get accurate, consistent EBM (Evidence Base Medicine) results. The children with pyramidal syndrome of juvenile cerebral palsy have been included in the examinations. The children have been divided into 2 random groups: group I--children treated with standard therapy a neurodevelopmental rehabilitation and classic kinesiotherapy, group II--hildren treated with standard therapy --eurodevelopmental rehabilitation, classic kinesiotherapy and a botulinum toxin. The children were examined three times: before the therapy, after 6 weeks of treatment and after 3 months of treatment. In the research BTS comprehensive motion analysis system have been used where influence of toxin botulin on walk stereotype of children was assessed. The treatment connected with standard rehabilitation and using botulinum toxin brings quicker walk improvement. Comparing the above treatment methods of influence on the walk stereotype of children with juvenile cerebral palsy, we can confirm, that standard treatment brings regular improvement, still, it requires longer period of time, often even 3 months. Using botulinum toxin brings quicker walk improvement, after 6 weeks only, which is a clear, but short-term result. Botulinum toxin has a positive effect on gait parameters in children, especially until 3 months, after this time parameters are not better..Concomitant treatment with standard therapy and botulinum toxin should be used becouse it is possitive treatment for locomotion of children with cerebral palsy.

Evidence for a single class of somatostatin receptors in ground squirrel cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krantic, S.; Petrovic, V.M.; Quirion, R.

1989-01-01

In the present study we characterized high-affinity somatostatin (SRIF) binding sites (Kd = 2.06 +/- 0.32 nM and Bmax = 295 +/- 28 fmol/mg protein) in cerebral cortex membrane preparations of European ground squirrel using /sup 125/I-(Tyr0-D-Trp8)-SRIF14 as a radioligand. The inhibition of radioligand specific binding by SRIF14, as well as by its agonists (SRIF28, Tyr0-D-Trp8-SRIF14, SMS 201 995) was complete and monophasic, thus revealing a single population of somatostatinergic binding sites. Radioautographic analysis of /sup 125/I-(Tyr0-D-Trp8)-SRIF14 labeled brain sections confirmed the results of our biochemical study. The homogeneity of SRIF binding sites in the ground squirrel neocortex was notmore » dependent on the animal's life-cycle phase.« less

Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

PubMed Central

Morales, Juan; Benavides-Piccione, Ruth; Pastor, Luis; Yuste, Rafael; DeFelipe, Javier

2014-01-01

Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns. PMID:22644869

A comparison of the effects of morphine, enkephalin, kyotorphin and D-phenylalanine on rat central neurones.

PubMed Central

Stone, T. W.

1983-01-01

1 Morphine, Met-enkephalin, kyotorphin and D-phenylalanine have been applied by microiontophoresis to neurones in the globus pallidus and cerebral cortex of rats anaesthetized with urethane. 2 In the pallidum, most cells were inhibited by all the agonists, with a high correspondence between cells inhibited by Met-enkephalin and D-phenylalanine and by Met-enkephalin and kyotorphin. Whereas responses to Met-enkephalin were readily antagonized by naloxone, responses to kyotorphin and D-phenylalanine were not. 3 In the cerebral cortex a high proportion of cells was excited by all four agonists and antagonism by naloxone was less consistent than in pallidum. 4 It is concluded that the naloxone-reversible analgesic effects of kyotorphin and D-phenylalanine may be mediated indirectly, rather through an activation of opiate receptors. PMID:6871550

A comparison of the effects of morphine, enkephalin, kyotorphin and D-phenylalanine on rat central neurones.

PubMed

Stone, T W

1983-05-01

1 Morphine, Met-enkephalin, kyotorphin and D-phenylalanine have been applied by microiontophoresis to neurones in the globus pallidus and cerebral cortex of rats anaesthetized with urethane. 2 In the pallidum, most cells were inhibited by all the agonists, with a high correspondence between cells inhibited by Met-enkephalin and D-phenylalanine and by Met-enkephalin and kyotorphin. Whereas responses to Met-enkephalin were readily antagonized by naloxone, responses to kyotorphin and D-phenylalanine were not. 3 In the cerebral cortex a high proportion of cells was excited by all four agonists and antagonism by naloxone was less consistent than in pallidum. 4 It is concluded that the naloxone-reversible analgesic effects of kyotorphin and D-phenylalanine may be mediated indirectly, rather through an activation of opiate receptors.

[Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Binding of L-[3H]glutamate to synaptic membranes of the rat cerebral cortex].

PubMed

Dambinova, S A; Gorodinskiĭ, A I

1984-01-01

The binding of L-[3H]glutamate to rat cerebral cortex synaptic membranes was investigated. Two types of binding sites, a Na+-independent (Kd = 140-160 nm; Bmax = 3.8-4.5 pmol-mg of protein) and a Na+-dependent (Kd = 2.0 microM; Bmax = 45-50 pmol/mg of protein) ones, were detected. The dependence of Na+-insensitive binding on time and temperature and membrane content in a sample was determined. Mono- and divalent cations (5-10 mM) potentiated specific binding by 2.1-3.3 times. The Na+-dependent binding is associated with active transport systems, while the Na+-independent one-with true receptor binding. The relationship between CNS glutamate receptors and Na+-independent binding sites is discussed.

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

PubMed Central

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-01-01

Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. Results: During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% (p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex (p < 0.001). Conclusions: α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses. PMID:28492488

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling.

PubMed

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-05-11

Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% ( p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex ( p < 0.001). α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses.

Different effects of transcutaneous electric nerve stimulation and electroacupuncture at ST36-ST37 on the cerebral cortex.

PubMed

Kang, Yu-Tien; Liao, Yi-Sheng; Hsieh, Ching-Liang

2015-02-01

The effects of transcutaneous electric nerve stimulation (TENS) and electroacupuncture (EA) on the cerebral cortex are largely unclear. The purpose of the present study was to investigate the effect of TENS and EA on the cerebral cortex by examining their effect on the median nerve-somatosensory evoked potentials (MN-SEPs). Twenty volunteers were studied. The cortical and cervical spinal potentials were recorded by median nerve stimulation at the left wrist. Sham TENS, 2 Hz TENS and 2 Hz EA were applied to both ST36 and ST37. MN-SEPs were recorded during sham TENS, 2 Hz TENS and 2 Hz EA, with at least 1 week interval for each subject. One-way analysis of variance was used to determine the differences in latency and amplitude of the MN-SEPs observed in the stimulation and post-stimulation periods compared with baseline. Scheffe's post hoc correction was employed to identify pairwise differences. No differences in mean latency were found between the stimulation procedures during the stimulation and post-stimulation periods. 2 Hz EA but not sham TENS or 2 Hz TENS caused higher mean amplitudes in N20 and N30 during the stimulation and post-stimulation periods. EA, but not TENS, induces changes in certain components of the signal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.