Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus.

PubMed

O'Riordan, Kenneth J; Hu, Neng-Wei; Rowan, Michael J

2018-02-20

Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble oligomers of amyloid-β (Aß) has been proposed to underlie synaptic dysfunction in Alzheimer's disease (AD). Previously, LTD was induced by relatively non-specific electrical stimulation. Exploiting optogenetics, we studied LTD using a more physiologically diffuse spatial pattern of selective pathway activation in the rat hippocampus in vivo. This relatively sparse synaptic LTD requires both the ion channel function and GluN2B subunit of the NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor activation. Although in the absence of Aß, there is no evidence of hippocampal LTD asymmetry, in the presence of Aß, the induction of LTD is preferentially enhanced in the left hippocampus in an mGluR5-dependent manner. This circuit-selective disruption of synaptic plasticity by Aß provides a route to understanding the development of aberrant brain lateralization in AD. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Age-dependent changes in vesicular glutamate transporter 1 and 2 expression in the gerbil hippocampus.

PubMed

Jung, Hyo Young; Yoo, Dae Young; Park, Joon Ha; Kim, Jong Whi; Chung, Jin Young; Kim, Dae Won; Won, Moo-Ho; Yoon, Yeo Sung; Hwang, In Koo

2018-05-01

Glutamate is a major excitatory neurotransmitter that is stored in vesicles located in the presynaptic terminal. Glutamate is transported into vesicles via the vesicular glutamate transporter (VGLUT). In the present study, the age‑associated changes of the major VGLUTs, VGLUT1 and VGLUT2, in the hippocampus were investigated, based on immunohistochemistry and western blot analysis at postnatal month 1 (PM1; adolescent), PM6, PM12 (adult group), PM18 and PM24 (the aged groups). VGLUT1 immunoreactivity was primarily detected in the mossy fibers, Schaffer collaterals and stratum lacunosum‑moleculare. By contrast, VGLUT2 immunoreactivity was observed in the granule cell layer and the outer molecular layer of the dentate gyrus, stratum pyramidale, Schaffer collaterals and stratum lacunosum‑moleculare in the hippocampal CA1‑3 regions. VGLUT1 immunoreactivity and protein levels remained constant across all age groups. However, VGLUT2 immunoreactivity and protein levels decreased in the PM3 group when compared with the PM1 group. VGLUT2 immunoreactivity and protein levels were not altered in the PM12 group; however, they increased in the PM18 group. In addition, in the PM18 group, highly immunoreactive VGLUT2 cells were also identified in the stratum radiatum and oriens of the hippocampal CA1 region. In the PM24 group, VGLUT2 immunoreactivity and protein levels were significantly decreased and were the lowest levels observed amongst the different groups. These results suggested that VGLUT1 may be less susceptible to the aging process; however, the increase of VGLUT2 in the non‑pyramidal cells in the PM18 group, and the consequent decrease in VGLUT2, may be closely linked to age‑associated memory impairment in the hippocampus.

Somatostatin type-2 receptor activation inhibits glutamate release and prevents status epilepticus

PubMed Central

Kozhemyakin, Maxim; Rajasekaran, Karthik; Todorovic, Marko S.; Kowalski, Samuel L.; Balint, Corinne; Kapur, Jaideep

2013-01-01

Summary Newer therapies are needed for the treatment of status epilepticus (SE) refractory to benzodiazepines. Enhanced glutamatergic neurotransmission leads to SE, and AMPA receptors are modified during SE. Reducing glutamate release during SE is a potential approach to terminate SE. The neuropeptide somatostatin (SST) is proposed to diminish presynaptic glutamate release by activating SST type-2 receptors (SST2R). SST exerts an anticonvulsant action in some experimental models of seizures. Here, we investigated the mechanism of action of SST on excitatory synaptic transmission at the Schaffer collateral-CA1 synapses and the ability of SST to treat SE in rats using patch-clamp electrophysiology and video-EEG monitoring of seizures. SST reduced action potential-dependent EPSCs (sEPSCs) at Schaffer collateral-CA1 synapses at concentrations up to 1 μM; higher concentrations had no effect or increased the sEPSC frequency. SST also prevented paired-pulse facilitation of evoked EPSCs and did not alter action-potential-independent miniature EPSCs (mEPSCs). The effect of SST on EPSCs was inhibited by the SST2R antagonist cyanamid-154806 and was mimicked by the SST2R agonists, octreotide and lanreotide. Both SST and octreotide reduced the firing rate of CA1 pyramidal neurons. Intraventricular administration of SST, within a range of doses, either prevented or attenuated pilocarpine-induced SE or delayed the median time to the first grade 5 seizure by 11 min. Similarly, octreotide or lanreotide prevented or attenuated SE in more than 65% of animals. Compared to the pilocarpine model, octreotide was highly potent in preventing or attenuating continuous hippocampal stimulation-induced SE in all animals within 60 min of SE onset. Our results demonstrate that SST, through the activation of SST2Rs, diminishes presynaptic glutamate release and attenuates SE. PMID:23473742

Age-dependent changes in vesicular glutamate transporter 1 and 2 expression in the gerbil hippocampus

PubMed Central

Jung, Hyo Young; Yoo, Dae Young; Park, Joon Ha; Kim, Jong Whi; Chung, Jin Young; Kim, Dae Won; Won, Moo-Ho; Yoon, Yeo Sung; Hwang, In Koo

2018-01-01

Glutamate is a major excitatory neurotransmitter that is stored in vesicles located in the presynaptic terminal. Glutamate is transported into vesicles via the vesicular glutamate transporter (VGLUT). In the present study, the age-associated changes of the major VGLUTs, VGLUT1 and VGLUT2, in the hippocampus were investigated, based on immunohistochemistry and western blot analysis at postnatal month 1 (PM1; adolescent), PM6, PM12 (adult group), PM18 and PM24 (the aged groups). VGLUT1 immunoreactivity was primarily detected in the mossy fibers, Schaffer collaterals and stratum lacunosum-moleculare. By contrast, VGLUT2 immunoreactivity was observed in the granule cell layer and the outer molecular layer of the dentate gyrus, stratum pyramidale, Schaffer collaterals and stratum lacunosum-moleculare in the hippocampal CA1-3 regions. VGLUT1 immunoreactivity and protein levels remained constant across all age groups. However, VGLUT2 immunoreactivity and protein levels decreased in the PM3 group when compared with the PM1 group. VGLUT2 immunoreactivity and protein levels were not altered in the PM12 group; however, they increased in the PM18 group. In addition, in the PM18 group, highly immunoreactive VGLUT2 cells were also identified in the stratum radiatum and oriens of the hippocampal CA1 region. In the PM24 group, VGLUT2 immunoreactivity and protein levels were significantly decreased and were the lowest levels observed amongst the different groups. These results suggested that VGLUT1 may be less susceptible to the aging process; however, the increase of VGLUT2 in the non-pyramidal cells in the PM18 group, and the consequent decrease in VGLUT2, may be closely linked to age-associated memory impairment in the hippocampus. PMID:29532891

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro

PubMed Central

Vida, Imre; Halasy, Katalin; Szinyei, Csaba; Somogyi, Peter; Buhl, Eberhard H

1998-01-01

Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n= 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n= 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n= 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n= 2) characterized by their dense, compact axonal and dendritic arbour. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynaptic pyramidal cells. Anatomically recovered R-LM interneurons (n= 22) had a mean resting membrane potential of -56.7 ± 3.6 mV, a membrane time constant of 12.9 ± 7.7 ms and an input resistance of 86.4 ± 29.2 MΩ. Depolarizing current pulses generally elicited overshooting action potentials (70.8 ± 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 ± 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. Basket cells, Schaffer-associated and neurogliaform interneurons elicited small-amplitude (< 2 mV), short-latency IPSPs in postsynaptic pyramids (n= 5, 13 and 1, respectively). Those interactions in which an effect was elicited with the repetitive activation of the presynaptic neuron (n= 13) showed a substantial degree of postsynaptic response summation. Unitary IPSPs had fast kinetics and, whenever tested (n= 5; 1 basket cell and 4 Schaffer-associated interneurons), were abolished by the GABAA receptor antagonist bicuculline. Thus, R-LM interneurons comprise several distinct populations which evoke fast GABAA receptor-mediated IPSPs. The domain-specific innervation of postsynaptic pyramidal cells suggests functionally diverse effects on the integration of afferent information in functionally non-equivalent compartments of pyramidal cells. PMID:9503336

Computed tomographic characteristics of collateral venous pathways in dogs with caudal vena cava obstruction.

PubMed

Specchi, Swan; d'Anjou, Marc-André; Carmel, Eric Norman; Bertolini, Giovanna

2014-01-01

Collateral venous pathways develop in dogs with obstruction or increased blood flow resistance at any level of the caudal vena cava in order to maintain venous drainage to the right atrium. The purpose of this retrospective study was to describe the sites, causes of obstruction, and configurations of venous collateral pathways for a group of dogs with caudal vena cava obstruction. Computed tomography databases from two veterinary hospitals were searched for dogs with a diagnosis of caudal vena cava obstruction and multidetector row computed tomographic angiographic (CTA) scans that included the entire caudal vena cava. Images for each included dog were retrieved and collateral venous pathways were characterized using image postprocessing and a classification system previously reported for humans. A total of nine dogs met inclusion criteria and four major collateral venous pathways were identified: deep (n = 2), portal (n = 2), intermediate (n = 7), and superficial (n = 5). More than one collateral venous pathway was present in 5 dogs. An alternative pathway consisting of renal subcapsular collateral veins, arising mainly from the caudal pole of both kidneys, was found in three dogs. In conclusion, findings indicated that collateral venous pathway patterns similar to those described in humans are also present in dogs with caudal vena cava obstruction. These collateral pathways need to be distinguished from other vascular anomalies in dogs. Postprocessing of multidetector-row CTA images allowed delineation of the course of these complicated venous pathways and may be a helpful adjunct for treatment planning in future cases. © 2014 American College of Veterinary Radiology.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-05-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed Central

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-01-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation. PMID:1975272

Deficits in cognitive function and hippocampal plasticity in GM2/GD2 synthase knockout mice.

PubMed

Sha, Sha; Zhou, Libin; Yin, Jun; Takamiya, Koga; Furukawa, Keiko; Furukawa, Koichi; Sokabe, Masahiro; Chen, Ling

2014-04-01

In this study, we used GM2/GD2 synthase knockout (GM2/GD2−/−) mice to examine the influence of deficiency in ganglioside “a-pathway” and “b-pathway” on cognitive performances and hippocampal synaptic plasticity. Eight-week-old GM2/GD2−/− male mice showed a longer escape-latency in Morris water maze test and a shorter latency in step-down inhibitory avoidance task than wild-type (WT) mice. Schaffer collateral-CA1 synapses in the hippocampal slices from GM2/GD2−/− mice showed an increase in the slope of EPSPs with reduced paired-pulse facilitation, indicating an enhancement of their presynaptic glutamate release. In GM2/GD2−/− mice, NMDA receptor (NMDAr)-dependent LTP could not be induced by high-frequency (100–200 Hz) tetanus or θ-burst conditioning stimulation (CS), whereas NMDAr-independent LTP was induced by medium-frequency CS (20–50 Hz). The application of mono-sialoganglioside GM1 in the slice from GM2/GD2−/− mice, to specifically recover the a-pathway, prevented the increased presynaptic glutamate release and 20 Hz-LTP induction, whereas it could not rescue the impaired NMDAr-dependent LTP. These findings suggest that b-pathway deficiency impairs cognitive function probably through suppression of NMDAr-dependent LTP, while a-pathway deficiency may facilitate NMDAr-independent LTP through enhancing presynaptic glutamate release. As both of the NMDAr-independent LTP and increased presynaptic glutamate release were sensitive to the blockade of L-type voltage-gated Ca2+ channels (L-VGCC), a-pathway deficiency may affect presynaptic L-VGCC.

Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1

PubMed Central

Booth, Clair A; Brown, Jonathan T; Randall, Andrew D

2014-01-01

A t(1;11) balanced chromosomal translocation transects the Disc1 gene in a large Scottish family and produces genome-wide linkage to schizophrenia and recurrent major depressive disorder. This study describes our in vitro investigations into neurophysiological function in hippocampal area CA1 of a transgenic mouse (DISC1tr) that expresses a truncated version of DISC1 designed to reproduce aspects of the genetic situation in the Scottish t(1;11) pedigree. We employed both patch-clamp and extracellular recording methods in vitro to compare intrinsic properties and synaptic function and plasticity between DISC1tr animals and wild-type littermates. Patch-clamp analysis of CA1 pyramidal neurons (CA1-PNs) revealed no genotype dependence in multiple subthreshold parameters, including resting potential, input resistance, hyperpolarization-activated ‘sag’ and resonance properties. Suprathreshold stimuli revealed no alteration to action potential (AP) waveform, although the initial rate of AP production was higher in DISC1tr mice. No difference was observed in afterhyperpolarizing potentials following trains of 5–25 APs at 50 Hz. Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio. Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input–output and short-term plasticity were also unaltered in the temporoammonic (TA) input. However, in DISC1tr mice theta burst-induced long-term potentiation was enhanced in the SC pathway but completely lost in the TA pathway. These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity. PMID:24712988

The effect of propofol on CA1 pyramidal cell excitability and GABAA-mediated inhibition in the rat hippocampal slice.

PubMed

Albertson, T E; Walby, W F; Stark, L G; Joy, R M

1996-05-24

An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of propofol on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid, and electrodes were placed in the CA1 region to record extracellular field population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. The major effect of propofol (7-28 microM) was a dose and time dependent increase in the intensity and duration of GABA-mediated inhibition. This propofol effect could be rapidly and completely reversed by exposure to known GABAA antagonists, including picrotoxin, bicuculline and pentylenetetrazol. It was also reversed by the chloride channel antagonist, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was not antagonized by central (flumazenil) or peripheral (PK11195) benzodiazepine antagonists. Reversal of endogenous inhibition was also noted with the antagonists picrotoxin and pentylenetetrazol. Input/output curves constructed using stimulus propofol caused only a small enhancement of EPSPs at higher stimulus intensities but had no effect on PS amplitudes. These studies are consistent with propofol having a GABAA-chloride channel mechanism causing its effect on recurrent collateral evoked inhibition in the rat hippocampal slice.

Potentiation of Schaffer-Collateral CA1 Synaptic Transmission by eEF2K and p38 MAPK Mediated Mechanisms.

PubMed

Weng, Weiguang; Chen, Ying; Wang, Man; Zhuang, Yinghan; Behnisch, Thomas

2016-01-01

The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity. The eEF2K-inhibition mediated potentiation of synaptic transmission of hippocampal CA1 neurons is most notably independent of protein synthesis and does not rely on protein kinase C, protein kinase A or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1/2. Moreover, the strengthening of synaptic transmission in the response to the inhibition of eEF2K was strongly attenuated by the inhibition of p38 MAPK. In addition, we show the involvement of barium-sensitive and more specific the TWIK-related potassium-1 (TREK-1) channels in the eEF2K-inhibition mediated potentiation of synaptic transmission. These findings reveal a novel pathway of eEF2K mediated regulation of hippocampal synaptic transmission. Further research is required to study whether such compounds could be beneficial for the development of mood disorder treatments with a fast-acting antidepressant response.

Tight coupling of astrocyte energy metabolism to synaptic activity revealed by genetically encoded FRET nanosensors in hippocampal tissue.

PubMed

Ruminot, Iván; Schmälzle, Jana; Leyton, Belén; Barros, L Felipe; Deitmer, Joachim W

2017-01-01

The potassium ion, K + , a neuronal signal that is released during excitatory synaptic activity, produces acute activation of glucose consumption in cultured astrocytes, a phenomenon mediated by the sodium bicarbonate cotransporter NBCe1 ( SLC4A4). We have explored here the relevance of this mechanism in brain tissue by imaging the effect of neuronal activity on pH, glucose, pyruvate and lactate dynamics in hippocampal astrocytes using BCECF and FRET nanosensors. Electrical stimulation of Schaffer collaterals produced fast activation of glucose consumption in astrocytes with a parallel increase in intracellular pyruvate and biphasic changes in lactate . These responses were blocked by TTX and were absent in tissue slices prepared from NBCe1-KO mice. Direct depolarization of astrocytes with elevated extracellular K + or Ba 2+ mimicked the metabolic effects of electrical stimulation. We conclude that the glycolytic pathway of astrocytes in situ is acutely sensitive to neuronal activity, and that extracellular K + and the NBCe1 cotransporter are involved in metabolic crosstalk between neurons and astrocytes. Glycolytic activation of astrocytes in response to neuronal K + helps to provide an adequate supply of lactate, a metabolite that is released by astrocytes and which acts as neuronal fuel and an intercellular signal.

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats.

PubMed

Gordon, Rita; Podolski, Igor; Makarova, Ekaterina; Deev, Alexander; Mugantseva, Ekaterina; Khutsyan, Sergey; Sengpiel, Frank; Murashev, Arkady; Vorobyov, Vasily

2017-01-01

Primary memory impairments associated with increased level of amyloid-β (Aβ) in the brain have been shown to be linked, partially, with early pathological changes in the entorhinal cortex (EC) which spread on the whole limbic system. While the hippocampus is known to play a key role in learning and memory mechanisms, it is as yet unclear how its structures are involved in the EC pathology. In this study, changes in memory and neuronal morphology in male Wistar rats intrahippocampally injected with Aβ25-35 were correlated on days 14 and 45 after the injection to reveal specific cognitive-structural associations. The main focus was on the dentate gyrus (DG) and hippocampal areas of CA1 and CA3 because of their involvement in afferent flows from EC to the hippocampus through tri-synaptic (EC → DG → CA3 → CA1) and/or mono-synaptic (EC → CA1) pathways. Evident memory impairments were observed at both time points after Aβ25-35 injection. However, on day 14, populations of morphological intact neurons were decreased in CA3 and, drastically, in CA1, and the DG supramedial bundle was significantly damaged. On day 45, this bundle largely and CA1 neurons partially recovered, whereas CA3 neurons remained damaged. We suggest that Aβ25-35 primarily affects the tri-synaptic pathway, destroying the granular cells in the DG supramedial area and neurons in CA3 and, through the Schaffer collaterals, in CA1. Intrahippocampal pretreatment with hydrated fullerene C60 allows the neurons and their connections to survive the amyloidosis, thus supporting the memory mechanisms.

High sucrose consumption induces memory impairment in rats associated with electrophysiological modifications but not with metabolic changes in the hippocampus.

PubMed

Lemos, C; Rial, D; Gonçalves, F Q; Pires, J; Silva, H B; Matheus, F C; da Silva, A C; Marques, J M; Rodrigues, R J; Jarak, I; Prediger, R D; Reis, F; Carvalho, R A; Pereira, F C; Cunha, R A

2016-02-19

High sugar consumption is a risk factor for metabolic disturbances leading to memory impairment. Thus, rats subject to high sucrose intake (HSu) develop a metabolic syndrome and display memory deficits. We now investigated if these HSu-induced memory deficits were associated with metabolic and electrophysiological alterations in the hippocampus. Male Wistar rats were submitted for 9 weeks to a sucrose-rich diet (35% sucrose solution) and subsequently to a battery of behavioral tests; after sacrifice, their hippocampi were collected for ex vivo high-resolution magic angle spinning (HRMAS) metabolic characterization and electrophysiological extracellular recordings in slices. HSu rats displayed a decreased memory performance (object displacement and novel object recognition tasks) and helpless behavior (forced swimming test), without altered locomotion (open field). HRMAS analysis indicated a similar hippocampal metabolic profile of HSu and control rats. HSu rats also displayed no change of synaptic transmission and plasticity (long-term potentiation) in hippocampal Schaffer fibers-CA1 pyramid synapses, but had decreased amplitude of long-term depression in the temporoammonic (TA) pathway. Furthermore, HSu rats had an increased density of inhibitory adenosine A1 receptors (A1R), that translated into a greater potency of A1R in Schaffer fiber synapses, but not in the TA pathway, whereas the endogenous activation of A1R in HSu rats was preserved in the TA pathway but abolished in Schaffer fiber synapses. These results suggest that HSu triggers a hippocampal-dependent memory impairment that is not associated with altered hippocampal metabolism but is probably related to modified synaptic plasticity in hippocampal TA synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The perforant path projection to hippocampal area CA1 in the rat hippocampal-entorhinal cortex combined slice.

PubMed

Empson, R M; Heinemann, U

1995-05-01

1. The perforant path projection from layer III of the entorhinal cortex to CA1 of the hippocampus was studied within a hippocampal-entorhinal combined slice preparation. We prevented contamination from the other main hippocampal pathways by removal of CA3 and the dentate gyrus. 2. Initially the projection was mapped using field potential recordings that suggested an excitatory sink in stratum lacunosum moleculare with an associated source in stratum pyramidale. 3. However, recording intracellularly from CA1 cells, stimulation of the perforant path produced prominent fast GABAA and slow GABAB IPSPs often preceded by small EPSPs. In a small number of cells we observed EPSPs only. 4. CNQX blocked excitatory and inhibitory responses. This indicated the presence of an intervening excitatory synapse between the inhibitory interneurone and the pyramidal cell. 5. Focal bicuculline applications revealed that the major site of GABAA inhibitory input was to stratum radiatum of CA1. 6. The inhibition activated by the perforant path was very effective at reducing simultaneously activated Schaffer collateral mediated EPSPs and suprathreshold-stimulated action potentials. 7. Blockade of fast inhibition increased excitability and enhanced slow inhibition. Both increases relied upon the activation of NMDA receptors. 8. Perforant path inputs activated prominent and effective disynaptic inhibition of CA1 cells. This has significance for the output of hippocampal processing during normal behaviour and also under pathological conditions.

Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter release.

PubMed

Choi, Tae-Yong; Kwon, Ji Eun; Durrance, Eunice Sung; Jo, Su-Hyun; Choi, Se-Young; Kim, Kyong-Tai

2014-04-04

Melatonin is involved in various neuronal functions such as circadian rhythmicity and thermoregulation. Melatonin has a wide range of pharmacologically effective concentration levels from the nanomolar to millimolar levels. Recently, the antiepileptic effect of high dose melatonin has been the focus of clinical studies; however, its detailed mechanism especially in relation to neurotransmitter release and synaptic transmission remains unclear. We studied the effect of melatonin at high concentrations on the neurotransmitter release by monitoring norepinephrine release in PC12 cells, and excitatory postsynaptic potential in rat hippocampal slices. Melatonin inhibits the 70mM K(+)-induced Ca(2+) increase at millimolar levels without effect on bradykinin-triggered Ca(2+) increase in PC12 cells. Melatonin (1mM) did not affect A2A adenosine receptor-evoked cAMP production, and classical melatonin receptor antagonists did not reverse the melatonin-induced inhibitory effect, suggesting G-protein coupled receptor independency. Melatonin inhibits the 70mM K(+)-induced norepinephrine release at a similar effective concentration range in PC12 cells. We confirmed that melatonin (100µM) inhibits excitatory synaptic transmission of the hippocampal Schaffer collateral pathway with the decrease in basal synaptic transmission and the increase in paired pulse ratio. These results show that melatonin inhibits neurotransmitter release through the blocking of voltage-sensitive Ca(2+) channels and suggest a possible mechanism for the antiepileptic effect of melatonin. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

PubMed

Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

2016-07-01

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. Copyright © 2016 the American Physiological Society.

ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity

PubMed Central

Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M. T.; Herrup, Karl

2016-01-01

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm−/− animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm−/− mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. PMID:27075534

Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca2+

PubMed Central

Scullin, Chessa S.; Partridge, L. Donald

2010-01-01

The presynaptic Ca2+ signal, which triggers vesicle release, disperses to a broadly distributed residual [Ca2+] ([Ca2+]res) that plays an important role in synaptic plasticity. We have previously reported a slowing in the decay timecourse of [Ca2+]res during the second of paired pulses. In this study, we investigated the contributions of organelle and plasma membrane Ca2+ flux pathways to the reduction of effectiveness of [Ca2+]res clearance during short-term plasticity in Schaffer collateral terminals in the CA1 field of the hippocampus. We show that the slowed decay timecourse is mainly the result of a transport-dependent Ca2+ clearance process; that presynaptic caffeine-sensitive Ca2+ stores are not functionally loaded in the unstimulated terminal, but that these stores can effectively take up Ca2+ even during high frequency trains of stimuli; and that a rate limiting step of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) kinetics following the first pulse is responsible for a large portion of the observed slowing of [Ca2+]res clearance during the second pulse. We were able to accurately fit our [Ca2+]res data with a kinetic model based on these observations and this model predicted a reduction in availability of unbound SERCA during paired pulses, but no saturation of Ca2+ buffer in the endoplasmic reticulum. PMID:20153896

Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons

PubMed Central

Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T.

2016-01-01

Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

PubMed

Chen, Kang; Neu, Axel; Howard, Allyson L; Földy, Csaba; Echegoyen, Julio; Hilgenberg, Lutz; Smith, Martin; Mackie, Ken; Soltesz, Ivan

2007-01-03

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

Molecular basis for impaired collateral artery growth in the spontaneously hypertensive rat: insight from microarray analysis

PubMed Central

Unthank, Joseph L; McClintick, Jeanette N; Labarrere, Carlos A; Li, Lang; DiStasi, Matthew R; Miller, Steven J

2013-01-01

Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals were similar between rat strains. Ingenuity® Pathway Analysis (IPA) identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were downregulated including JUN (−5.2×, P = 0.02), EGR1 (−4.1×, P = 0.01), and NFĸB1 (−1.95×, P = 0.04). Predicted binding sites for NFĸB and AP-1 were present in genes altered in WKY but not SHR collaterals. Immunostaining showed increased NFĸB nuclear translocation in collateral arteries of WKY and apocynin-treated SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral growth in WKY, confirming a functional role of NFkB. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin–angiotensin system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1 with losartan prevented collateral luminal expansion in WKY. Together, these results suggest that collateral growth impairment results from an abnormality in a fundamental regulatory mechanism that occurs at a level between signal transduction and gene transcription and implicate redox-dependent modulation of mechano-sensitive transcription factors such as NFĸB as a potential mechanism. PMID:24303120

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

PubMed

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-07-08

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

Critical role of canonical transient receptor potential channel 7 in initiation of seizures.

PubMed

Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2014-08-05

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.

Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell excitability in the rat hippocampal slice.

PubMed

Joy, R M; Walby, W F; Stark, L G; Albertson, T E

1995-01-01

An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed analyses of the effects of lindane. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. Perfusion with lindane produced both time and dose dependent changes in a number of the responses measured. The most striking effect produced by lindane was the loss of GABAA-mediated recurrent collateral inhibition. This tended to occur rapidly, often before changes in EPSP or PS responses could be detected. With longer exposures to lindane, repetitive discharge of pyramidal cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM) also completely reversed the effects of the injectable anesthetic, propofol, a compound known to potentiate GABAA-mediated inhibition via a direct action on the GABAA receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed that lindane increased EPSP and PS response amplitudes at any given stimulus intensity resulting in a leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low intensity stimuli and became progressively less so as stimulus intensities approached those yielding maximal responses. In addition lindane significantly increased paired pulse facilitation of EPSPs during paired stimulus presentation.

Physiological properties of anatomically identified basket and bistratified cells in the CA1 area of the rat hippocampus in vitro.

PubMed

Buhl, E H; Szilágyi, T; Halasy, K; Somogyi, P

1996-01-01

Basket and bistratified cells form two anatomically distinct classes of GABAergic local-circuit neurons in the CA1 region of the rat hippocampus. A physiological comparison was made of intracellularly recorded basket (n = 13) and bistratified neurons (n = 6), all of which had been anatomically defined by their efferent target profile (Halasy et al., 1996). Basket cells had an average resting membrane potential of -64.2 +/- 7.2 vs. -69.2 +/- 4.6 mV in bistratified cells. The latter had considerably higher mean input resistances (60.2 +/- 42.1 vs. 31.3 +/- 10.9 M Ohms) and longer membrane time constants (18.6 +/- 8.1 vs. 9.8 +/- 4.5 ms) than basket cells. Differences were also apparent in the duration of action potentials, those of basket cells being 364 +/- 77 and those of bistratified cells being 527 +/- 138 microseconds at half-amplitude. Action potentials were generally followed by prominent, fast after-hyperpolarizing potentials which in basket cells were 13.5 +/- 6.7 mV in amplitude vs. 10.5 +/- 5.1 in bistratified cells. The differences in membrane time constant, resting membrane potential, and action potential duration reached statistical significance (P < 0.05). Extracellular stimulation of Schaffer collateral/commissural afferents elicited short-latency excitatory postsynaptic potentials (EPSPs) in both cell types. The average 10-90% rise time and duration (at half-amplitude) of subthreshold EPSPs in basket cells were 1.9 +/- 0.5 and 10.7 +/- 5.6 ms, compared to 3.3 +/- 1.3 and 20.1 +/- 9.7 ms in bistratified cells, the difference in EPSP rise times being statistically significant. Basket and bistratified EPSPs were highly sensitive to a bath applied antagonist of non-N-methyl-D-aspartate (NMDA) receptors, whereas the remaining slow-rise EPSP could be abolished by an NMDA receptor antagonist. Increasing stimulation intensity elicited biphasic inhibitory postsynaptic potentials (IPSPs) in both basket and bistratified cells. In conclusion, basket and bistratified cells in the CA1 area show prominent differences in several of their membrane and firing properties. Both cell classes are activated by Schaffer collateral/commissural axons in a feedforward manner and receive inhibitory input from other, as yet unidentified, local-circuit neurons.

Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

PubMed

Smith, Lindsey A; McMahon, Lori L

2018-02-01

Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides support for this model as a valuable preclinical tool in elucidating pathological mechanisms of early synapse dysfunction in AD. Copyright © 2017. Published by Elsevier Inc.

Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory

PubMed Central

Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M.

2015-01-01

Abstract Aims: This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Results: Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. Innovation and Conclusion: These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment. Antioxid. Redox Signal. 23, 695–710. PMID:25843188

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall

PubMed Central

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-01-01

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall. DOI: http://dx.doi.org/10.7554/eLife.02839.001 PMID:25006034

Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation.

PubMed

Teixeira, Catia M; Rosen, Zev B; Suri, Deepika; Sun, Qian; Hersh, Marc; Sargin, Derya; Dincheva, Iva; Morgan, Ashlea A; Spivack, Stephen; Krok, Anne C; Hirschfeld-Stoler, Tessa; Lambe, Evelyn K; Siegelbaum, Steven A; Ansorge, Mark S

2018-06-06

The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known. Here we applied optogenetic techniques in mice to gain insight into this fundamental biological process. We find that activation of serotonergic terminals in the hippocampal CA1 region both potentiates excitatory transmission at CA3-to-CA1 synapses and enhances spatial memory. Conversely, optogenetic silencing of CA1 5-HT terminals inhibits spatial memory. We furthermore find that synaptic potentiation is mediated by 5-HT4 receptors and that systemic modulation of 5-HT4 receptor function can bidirectionally impact memory formation. Collectively, these data reveal powerful modulatory influence of serotonergic synaptic input on hippocampal function and memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

PubMed

Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

2015-01-01

Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices.

PubMed

Hamon, B; Stanton, P K; Heinemann, U

1987-03-31

Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices.

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

PubMed Central

Hurtado-Zavala, Joaquin I.; Ramachandran, Binu; Ahmed, Saheeb; Halder, Rashi; Bolleyer, Christiane; Awasthi, Ankit; Stahlberg, Markus A.; Wagener, Robin J.; Anderson, Kristin; Drenan, Ryan M.; Lester, Henry A.; Miwa, Julie M.; Staiger, Jochen F.; Fischer, Andre; Dean, Camin

2017-01-01

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity. PMID:28722015

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination

PubMed Central

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K.; Tikhobrazova, Olga; Wulff, Andreas B.; Mironov, Andrey; van Kuppevelt, Toin H.; Oosterhof, Arie; Kochlamazashvili, Gaga

2017-01-01

Abstract Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3–CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. PMID:28119345

Exfoliative dermatitis

MedlinePlus

Bolognia JL, Schaffer JV, Duncan KO, Ko CJ. Erythroderma. In: Bolognia JL, Schaffer JV, Duncan KO, Ko CJ, eds. Dermatology Essentials. Philadelphia, PA: Elsevier; 2014:chap 8. Habif TP. Exanthems and ...

Visualization and Classification of Deeply Seated Collateral Networks in Moyamoya Angiopathy with 7T MRI.

PubMed

Matsushige, T; Kraemer, M; Sato, T; Berlit, P; Forsting, M; Ladd, M E; Jabbarli, R; Sure, U; Khan, N; Schlamann, M; Wrede, K H

2018-06-07

Collateral networks in Moyamoya angiopathy have a complex angioarchitecture difficult to comprehend on conventional examinations. This study aimed to evaluate morphologic patterns and the delineation of deeply seated collateral networks using ultra-high-field MRA in comparison with conventional DSA. Fifteen white patients with Moyamoya angiopathy were investigated in this prospective trial. Sequences acquired at 7T were TOF-MRA with 0.22 × 0.22 × 0.41 mm 3 resolution and MPRAGE with 0.7 × 0.7 × 0.7 mm 3 resolution. Four raters evaluated the presence of deeply seated collateral networks and image quality in a consensus reading of DSA, TOF-MRA, and MPRAGE using a 5-point scale in axial source images and maximum intensity projections. Delineation of deeply seated collateral networks by different imaging modalities was compared by means of the McNemar test, whereas image quality was compared using the Wilcoxon signed-rank test. The relevant deeply seated collateral networks were classified into 2 categories and 6 pathways. A total of 100 collateral networks were detected on DSA; 106, on TOF-MRA; and 73, on MPRAGE. Delineation of deeply seated collateral networks was comparable between TOF-MRA and DSA ( P = .25); however, both were better than MPRAGE ( P < .001). This study demonstrates excellent delineation of 6 distinct deeply seated collateral network pathways in Moyamoya angiopathy in white adults using 7T TOF-MRA, comparable to DSA. © 2018 by American Journal of Neuroradiology.

Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron

PubMed Central

Ishikawa, Yasuyuki; Tamura, Hideki; Shiosaka, Sadao

2011-01-01

Abstract Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer collateral pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging. PMID:21646406

A Comparison of Different Slicing Planes in Preservation of Major Hippocampal Pathway Fibers in the Mouse

PubMed Central

Xiong, Guoxiang; Metheny, Hannah; Johnson, Brian N.; Cohen, Akiva S.

2017-01-01

The hippocampus plays a critical role in learning and memory and higher cognitive functions, and its dysfunction has been implicated in various neuropathological disorders. Electrophysiological recording undertaken in live brain slices is one of the most powerful tools for investigating hippocampal cellular and network activities. The plane for cutting the slices determines which afferent and/or efferent connections are best preserved, and there are three commonly used slices: hippocampal-entorhinal cortex (HEC), coronal and transverse. All three slices have been widely used for studying the major afferent hippocampal pathways including the perforant path (PP), the mossy fibers (MFs) and the Schaffer collaterals (SCs). Surprisingly, there has never been a systematic investigation of the anatomical and functional consequences of slicing at a particular angle. In the present study, we focused on how well fiber pathways are preserved from the entorhinal cortex (EC) to the hippocampus, and within the hippocampus, in slices generated by sectioning at different angles. The postmortem neural tract tracer 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (DiI) was used to label afferent fibers to hippocampal principal neurons in fixed slices or whole brains. Laser scanning confocal microscopy was adopted for imaging DiI-labeled axons and terminals. We demonstrated that PP fibers were well preserved in HEC slices, MFs in both HEC and transverse slices and SCs in all three types of slices. Correspondingly, field excitatory postsynaptic potentials (fEPSPs) could be consistently evoked in HEC slices when stimulating PP fibers and recorded in stratum lacunosum-moleculare (sl-m) of area CA1, and when stimulating the dentate granule cell layer (gcl) and recording in stratum lucidum (sl) of area CA3. The MF evoked fEPSPs could not be recorded in CA3 from coronal slices. In contrast to our DiI-tracing data demonstrating severely truncated PP fibers in coronal slices, fEPSPs could still be recorded in CA1 sl-m in this plane, suggesting that an additional afferent fiber pathway other than PP might be involved. The present study increases our understanding of which hippocampal pathways are best preserved in the three most common brain slice preparations, and will help investigators determine the appropriate slices to use for physiological studies depending on the subregion of interest. PMID:29201002

Hippocampal closed-loop modeling and implications for seizure stimulation design

NASA Astrophysics Data System (ADS)

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2015-10-01

Objective. Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main results. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Influence of slow oscillation on hippocampal activity and ripples through cortico-hippocampal synaptic interactions, analyzed by a cortical-CA3-CA1 network model.

PubMed

Taxidis, Jiannis; Mizuseki, Kenji; Mason, Robert; Owen, Markus R

2013-01-01

Hippocampal sharp wave-ripple complexes (SWRs) involve the synchronous discharge of thousands of cells throughout the CA3-CA1-subiculum-entorhinal cortex axis. Their strong transient output affects cortical targets, rendering SWRs a possible means for memory transfer from the hippocampus to the neocortex for long-term storage. Neurophysiological observations of hippocampal activity modulation by the cortical slow oscillation (SO) during deep sleep and anesthesia, and correlations between ripples and UP states, support the role of SWRs in memory consolidation through a cortico-hippocampal feedback loop. We couple a cortical network exhibiting SO with a hippocampal CA3-CA1 computational network model exhibiting SWRs, in order to model such cortico-hippocampal correlations and uncover important parameters and coupling mechanisms controlling them. The cortical oscillatory output entrains the CA3 network via connections representing the mossy fiber input, and the CA1 network via the temporoammonic pathway (TA). The spiking activity in CA3 and CA1 is shown to depend on the excitation-to-inhibition ratio, induced by combining the two hippocampal inputs, with mossy fiber input controlling the UP-state correlation of CA3 population bursts and corresponding SWRs, whereas the temporoammonic input affects the overall CA1 spiking activity. Ripple characteristics and pyramidal spiking participation to SWRs are shaped by the strength of the Schaffer collateral drive. A set of in vivo recordings from the rat hippocampus confirms a model-predicted segregation of pyramidal cells into subgroups according to the SO state where they preferentially fire and their response to SWRs. These groups can potentially play distinct functional roles in the replay of spike sequences.

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy

PubMed Central

Booth, Clair A.; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W.; Randall, Andrew D.

2016-01-01

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. PMID:26758828

Ephrin-B2 prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity.

PubMed

Planagumà, Jesús; Haselmann, Holger; Mannara, Francesco; Petit-Pedrol, Mar; Grünewald, Benedikt; Aguilar, Esther; Röpke, Luise; Martín-García, Elena; Titulaer, Maarten J; Jercog, Pablo; Graus, Francesc; Maldonado, Rafael; Geis, Christian; Dalmau, Josep

2016-09-01

To demonstrate that ephrin-B2 (the ligand of EphB2 receptor) antagonizes the pathogenic effects of patients' N-methyl-D-aspartate receptor (NMDAR) antibodies on memory and synaptic plasticity. One hundred twenty-two C57BL/6J mice infused with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, with or without ephrin-B2, were investigated. CSF was infused through ventricular catheters connected to subcutaneous osmotic pumps over 14 days. Memory, behavioral tasks, locomotor activity, presence of human antibodies specifically bound to hippocampal NMDAR, and antibody effects on the density of cell-surface and synaptic NMDAR and EphB2 were examined at different time points using reported techniques. Short- and long-term synaptic plasticity were determined in acute brain sections; the Schaffer collateral pathway was stimulated and the field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus. Mice infused with patients' CSF, but not control CSF, developed progressive memory deficit and depressive-like behavior along with deposits of NMDAR antibodies in the hippocampus. These findings were associated with a decrease of the density of cell-surface and synaptic NMDAR and EphB2, and marked impairment of long-term synaptic plasticity without altering short-term plasticity. Administration of ephrin-B2 prevented the pathogenic effects of the antibodies in all the investigated paradigms assessing memory, depressive-like behavior, density of cell-surface and synaptic NMDAR and EphB2, and long-term synaptic plasticity. Administration of ephrin-B2 prevents the pathogenic effects of anti-NMDAR encephalitis antibodies on memory and behavior, levels of cell-surface NMDAR, and synaptic plasticity. These findings reveal a strategy beyond immunotherapy to antagonize patients' antibody effects. Ann Neurol 2016;80:388-400. © 2016 American Neurological Association.

Hippocampal closed-loop modeling and implications for seizure stimulation design.

PubMed

Sandler, Roman A; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W; Marmarelis, Vasilis Z

2015-10-01

Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal Closed-Loop Modeling and Implications for Seizure Stimulation Design

PubMed Central

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2016-01-01

Objective Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the Entorhinal Cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3→CA1, via the Schaffer-Collateral synapse, and CA1→CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (Principal Dynamic Modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main Results Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance DBS is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID:26355815

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

PubMed

Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

2016-01-13

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.

PubMed

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K; Tikhobrazova, Olga; Wulff, Andreas B; Mironov, Andrey; van Kuppevelt, Toin H; Oosterhof, Arie; Kochlamazashvili, Gaga; Dityatev, Alexander; Henneberger, Christian

2017-02-01

Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. © The Author 2017. Published by Oxford University Press.

Role of collateral paths in long-range diffusion in lungs

PubMed Central

Bartel, Seth-Emil T.; Haywood, Susan E.; Woods, Jason C.; Chang, Yulin V.; Menard, Christopher; Yablonskiy, Dmitriy A.; Gierada, David S.; Conradi, Mark S.

2010-01-01

The long-range apparent diffusion coefficient (LRADC) of 3He gas in lungs, measured over times of several seconds and distances of 1–3 cm, probes the connections between the airways. Previous work has shown the LRADC to be small in health and substantially elevated in emphysema, reflecting tissue destruction, which is known to create collateral pathways. To better understand what controls LRADC, we report computer simulations and measurements of 3He gas diffusion in healthy lungs. The lung is generated with a random algorithm using well-defined rules, yielding a three-dimensional set of nodes or junctions, each connected by airways to one parent node and two daughters; airway dimensions are taken from published values. Spin magnetization in the simulated lung is modulated sinusoidally, and the diffusion equation is solved to 1,000 s. The modulated magnetization decays with a time constant corresponding to an LRADC of ~0.001 cm2/s, which is smaller by a factor of ~20 than the values in healthy lungs measured here and previously in vivo and in explanted lungs. It appears that collateral gas pathways, not present in the simulations, are functional in healthy lungs; they provide additional and more direct routes for long-range motion than the canonical airway tree. This is surprising, inasmuch as collateral ventilation is believed to be physiologically insignificant in healthy lungs. We discuss the effect on LRADC of small collateral connections through airway walls and rule out other possible mechanisms. The role of collateral paths is supported by measurements of smaller LRADC in pigs, where collateral ventilation is known to be smaller. PMID:18292298

The effects of lindane and long-term potentiation (LTP) on pyramidal cell excitability in the rat hippocampal slice.

PubMed

Albertson, T E; Walby, W F; Stark, L G; Joy, R M

1997-01-01

An in vitro orthodromic stimulation technique was used to examine the effects of lindane and long-term potentiation (LTP) inducing stimuli, alone or in combination, on the excitatory afferent terminal of CA1 pyramidal cells and on recurrent collateral evoked inhibition using the rat hippocampal slice model. Hippocampal slices of 400 microns thickness were perfused with oxygenated artificial cerebrospinal fluid. Stimulation of Schaffer collateral/commissural fibers produced extracellular excitatory postsynaptic potential (EPSP) and/or populations spike (PS) responses recorded from electrodes in the CA1 region. A paired-pulse technique was used to measure gamma-aminobutyric acid (GABAA)-mediated recurrent inhibition before and after treatments. After both lindane and LTP, larger PS amplitudes for a given stimulus intensity were seen. The resulting leftward shift in the curve of the PS amplitude versus stimulus intensity was larger after LTP than after 25 microM lindane. Both lindane and LTP treatments reduced PS thresholds and reduced or eliminated recurrent inhibition as measured by paired-pulse stimulation at the 15 msec interval. The reduction of recurrent inhibition after both treatments was more pronounced at lower stimulus intensities. When LTP stimuli were applied after lindane exposure a further large shift to the left was seen in the PS amplitude versus stimulus intensity curve. A smaller shift to the left was seen in the PS amplitude versus stimulus intensity curve only at the higher stimuli when lindane exposure occurred after LTP. Only at low stimulus intensities were further argumentations seen in PS amplitudes when the LTP stimuli was followed by a second LTP stimuli. Previous exposure to 25 microM lindane stimuli does not block the development of a further robust LTP in this in vitro model.

Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy.

PubMed

Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam

2017-03-14

Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy

PubMed Central

Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam

2017-01-01

Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management. PMID:28348478

Experimental study of hemodynamics in the Circle of Willis.

PubMed

Zhu, Guangyu; Yuan, Qi; Yang, Jian; Yeo, Joon

2015-01-01

The Circle of Willis (CoW) is an important collateral pathway of the cerebral blood flow. An experimental study of the cerebral blood flow (CBF) distribution in different anatomical variations may help to a better understanding of the collateral mechanism of the CoW. An in-vitro test rig was developed to simulate the physiological cerebral blood flow in the CoW. Ten anatomical variations were considered in this study, include a set of different degrees of stenosis in L-ICA and L-ICA occlusion coexist with common anatomical variations. Volume flow rates of efferent arteries and pressure signals at the end of communicating arteries of each case were recorded. Physiological pressure waveforms were applied as inlet boundary condition. In the development of L-ICA stenosis, the total CBF decreases with the increase of stenosis degree. The blood supply of ipsilateral middle cerebral artery (MCA) was affected most by the stenosis of L-ICA. Anterior communicating artery (ACoA) and ipsilateral posterior communicating artery (PCoA) function as important collateral pathways of cerebral collateral circulation when unilateral stenosis occurred. The blood supply of anterior cerebral circulation was compensated by the posterior cerebral circulation through ipsilateral PCoA when L-ICA stenosis degree is greater than 40% and the affected side was compensated immediately by the unaffected side through ACoA. Blood flow of the anterior circulation and the total CBF reached the minimum among all cases studied when L-ICA occlusion coexist with the absence of PCoA. The results demonstrated the flow distribution patterns of the CoW under anatomical variations and clarified the collateral mechanism of the CoW. The flow ACoA is the most sensitive indexes to the morphology change of ipsilateral ICA. The relative independence of the circulation in anterior and posterior sections of the CoW is not broken and the function of ipsilateral PCoA is not activated until a severe stenosis of unilateral ICA occurs. PCoA is the most important collateral pathway of the collateral circulation and the missing of PCoA has the highest risk of stroke when the ipsilateral ICA has severe stenosis. These findings may provide the basis for future therapeutic and diagnosis applications.

Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Flow Direction Reversal

PubMed Central

Heuslein, Joshua L.; Meisner, Joshua K.; Li, Xuanyue; Song, Ji; Vincentelli, Helena; Leiphart, Ryan J.; Ames, Elizabeth G.; Price, Richard J.

2015-01-01

Objective Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of flow direction reversal, occurring in numerous collateral artery segments after femoral artery ligation (FAL), is unknown. Our objective was to determine if flow direction reversal in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. Approach and Results Collateral segments experiencing flow reversal after FAL in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post-FAL) remodeling. Genome-wide transcriptional analyses on HUVECs exposed to flow reversal conditions mimicking those occurring in-vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (NFκB, VEGF, FGF2, TGFβ) and arteriogenic canonical pathways (PKA, PDE, MAPK). Augmented expression of key pro-arteriogenic molecules (KLF2, ICAM-1, eNOS) was also verified by qRT-PCR, leading us to test whether ICAM-1 and/or eNOS regulate amplified arteriogenesis in flow-reversed collateral segments in-vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after FAL in ICAM-1−/− mice; however, eNOS−/− mice showed no such differences. Conclusions Flow reversal leads to a broad amplification of pro-arteriogenic endothelial signaling and a sustained ICAM-1-dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by flow reversal may lead to more effective and durable therapeutic options for arterial occlusive diseases. PMID:26338297

Extrahepatic Blood Supply to Hepatocellular Carcinoma: Angiographic Demonstration and Transcatheter Arterial Chemoembolization

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

Miyayama, Shiro; Matsui, Osamu; Taki, Keiichi

2006-02-15

Purpose. To evaluate the incidence of each extrahepatic collateral pathway to hepatocellular carcinoma (HCC) and to assess technical success rates and complications of transcatheter arterial chemoembolization (TACE) through each collateral. Methods. We retrospective evaluated extrahepatic collateral pathways to HCC on angiography in 386 procedures on 181 consecutive patients. One hundred and seventy patients had previously undergone TACE. TACE through extrahepatic collaterals using iodized oil and gelatin sponge particles was performed when a catheter was advanced into the tumor-feeding branch to avoid nontarget embolization. Results. A single collateral was revealed in 275 TACE procedures, two were revealed in 74, and threemore » or more were revealed in 34. Incidences of collateral source to HCC were 83% from the right inferior phrenic artery (IPA), 24% from the cystic artery, 13% from the omental artery, 12% from the right renal capsular artery (RCA) and left IPA, 8% from the right internal mammary artery (IMA) and right intercostal artery (ICA), and 7% from the right inferior adrenal artery (IAA). Technical success rates of TACE were 53% in the right ICA, 70% in the cystic artery, 74% in the omental artery, 93% in the left IPA, 96% in the right IPA, and 100% in the right RCA, right IMA, and right IAA. Complications included skin necrosis after TACE through the right IMA (n = 1), cholecystitis after TACE through the cystic artery (n = 1), and ulcer formation after TACE through the right gastric artery (n = 1), in addition to pleural effusion and basal atelectasis after TACE through the IPA and IMA. Conclusion. Our study suggests that TACE through extrahepatic collaterals is possible with high success rates, and is also relatively safe.« less

p27(kip1) Knockout enhances collateralization in response to hindlimb ischemia.

PubMed

Ankri-Eliahoo, Galit; Weitz, Kevin; Cox, Timothy C; Tang, Gale L

2016-05-01

The natural response to arterial occlusive disease is enlargement of collaterals; however, the molecular factors that control collateralization are not well understood. The gene p27(Kip1) (p27) affects human response to arterial injury. Previous studies have shown that overexpression of p27 inhibits vascular endothelial and vascular smooth muscle cell (VSMC) proliferation and angiogenesis. To test the hypothesis that knockout of p27 would improve collateralization in reaction to ischemia, we performed in vivo and in vitro experiments using p27 knockout (p27(-/-)) and wild-type (wt) mice. Hindlimb ischemia was induced by left femoral artery ligation in p27(-/-) and wt (C57BL/6) female mice. The mice underwent weekly laser Doppler perfusion imaging of the footpads until sacrifice on postoperative day 28 followed by microcomputed tomography scanning of both hindlimbs. VSMCs were isolated from p27(-/-) and wt mice and used in migration and gel contraction assays in the absence and presence of the nonspecific matrix metalloproteinase (MMP) inhibitor BB94. MMP-2 and MMP-9 messenger RNA (mRNA) expression was measured by quantitative reverse transcription-polymerase chain reaction in p27(-/-) and wt VSMCs. p27(-/-) mice reperfused more effectively than wt mice by laser Doppler starting from day 7 (ischemic/nonischemic ratio, 0.33 ± 0.02 vs 0.25 ± 0.02; P < .05) and continuing through day 28 (0.45 ± 0.04 vs 0.31 ± 0.04; P < .05). The gracilis collateral diameter was similar for the nonischemic hindlimbs of the p27(-/-) and wt mice, and this collateral pathway increased similarly after ischemia as assessed by microcomputed tomography. However, the p27(-/-) mice significantly enlarged a novel collateral pathway that bridged directly between the femoral artery proximal to the ligation site and the saphenous or popliteal artery distal to the ligation site more than wt mice (158 ± 18.3 vs 82 ± 22 μm; P < .001). p27(-/-) VSMCs migrated more (79% ± 5% vs 56% ± 6%; P < .05) and caused more gel contraction (18% ± 5% of the initial area vs 43% ± 4%; P < .05) than wt cells. Migration and collagen contraction were abolished in p27(-/-) and wt cells by MMP inhibition. p27(-/-) cells expressed significantly more MMP-2 mRNA than wt cells did. Knockout of p27 enhances arterial collateralization in response to hindlimb ischemia through enlargement of a new collateral pathway. In vitro, knockout of p27 increases collagen gel contraction in addition to stimulating VSMC migration. We speculate that p27 may affect collateralization through its role in regulating MMP-2 expression. Published by Elsevier Inc.

Regulation of GABAA and Glutamate Receptor Expression, Synaptic Facilitation and Long-Term Potentiation in the Hippocampus of Prion Mutant Mice

PubMed Central

Rangel, Alejandra; Madroñal, Noelia; Massó, Agnès Gruart i.; Gavín, Rosalina; Llorens, Franc; Sumoy, Lauro; Torres, Juan María; Delgado-García, José María; Río, José Antonio Del

2009-01-01

Background Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrPsc) of the natural cellular prion protein (PrPc) encoded by the Prnp gene. Although several roles have been attributed to PrPc, its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrPc studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. Methodology/Principal Findings Here we explore the role of PrPc expression in neurotransmission and neural excitability using wild-type, Prnp −/− and PrPc-overexpressing mice (Tg20 strain). By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp −/− mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina™ microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp −/− and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABAA and AMPA-kainate receptors are co-regulated in both Prnp −/− and Tg20 mice. Conclusions/Significance Present results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its relationships with GABAA and AMPA-Kainate neurotransmission. New PrPc functions have recently been described, which point to PrPc as a target for putative therapies in Alzheimer's disease. However, our results indicate that a “gain of function” strategy in Alzheimer's disease, or a “loss of function” in prionopathies, may impair PrPc function, with devastating effects. In conclusion, we believe that present data should be taken into account in the development of future therapies. PMID:19855845

Role of AMPA and NMDA receptors and back-propagating action potentials in spike timing-dependent plasticity.

PubMed

Fuenzalida, Marco; Fernández de Sevilla, David; Couve, Alejandro; Buño, Washington

2010-01-01

The cellular mechanisms that mediate spike timing-dependent plasticity (STDP) are largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC) excitatory postsynaptic potentials (EPSPs; EPSP(AMPA) and EPSP(NMDA)) and of the back-propagating action potential (BAP) to the long-term potentiation (LTP) induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSP(AMPA) with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSP(AMPA) by combining SC stimulation, an imposed EPSP(AMPA)-like depolarization, and BAP or by coupling the EPSP(NMDA) evoked under sustained depolarization (approximately -40 mV) and BAP. In Mg(2+)-free solution EPSP(NMDA) and BAP also produced LTP. Suppression of EPSP(NMDA) or BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed but not sufficient because AMPA receptor activation is also obligatory for STDP. However, a transient depolarization of another origin that unblocks NMDA receptors and a BAP may also trigger LTP.

Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer's disease.

PubMed

Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

2015-11-01

Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

Input Source and Strength Influences Overall Firing Phase of Model Hippocampal CA1 Pyramidal Cells During Theta: Relevance to REM Sleep Reactivation and Memory Consolidation

PubMed Central

Booth, Victoria; Poe, Gina R.

2005-01-01

In simulation studies using a realistic model CA1 pyramidal cell, we accounted for the shift in mean firing phase from theta cycle peaks to theta cycle troughs during REM sleep reactivation of hippocampal CA1 place cells over several days of growing familiarization with an environment (Poe et al., 2000). Changes in the theta drive between proximal and distal dendritic regions of the cell modulated the theta phase of firing when stimuli were presented at proximal and distal dendritic locations. Stimuli at proximal dendritic sites (proximal to 100 μm from the soma) invoked firing with a significant phase preference at the depolarizing theta peaks, while distal stimuli (> 290 μm from the soma) invoked firing at hyperpolarizing theta troughs. The location-related phase preference depended on active dendritic conductances, a sufficient electrotonic separation between input sites and theta-induced subthreshold membrane potential oscillations in the cell. The simulation results predict that the shift in mean theta phase during REM sleep cellular reactivation could occur through potentiation of distal dendritic (temporo-ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral) synapses over the course of familiarization. PMID:16411243

Differential regulation of GluA1 expression by ketamine and memantine.

PubMed

Zhang, Ke; Yamaki, Vitor Nagai; Wei, Zhisheng; Zheng, Yu; Cai, Xiang

2017-01-01

Evidence from preclinical and clinical studies shows that ketamine, a noncompetitive NMDA receptor antagonist, exerts rapid and sustained antidepressant responses. However, ketamine's psychotomimetic side effects and abuse liability limit the clinical use of the compound. Interestingly, memantine, another NMDA receptor channel blocker, processes no defined antidepressant property but is much safer and clinical tolerated. Understanding why ketamine but not memantine exhibits rapid antidepressant responses is important to elucidate the cellular signaling underlying the fast antidepressant actions of ketamine and to design a new safer generation of fast-acting antidepressants. Here we show that ketamine but memantine caused a rapid and sustained antidepressant-like responses in forced swim test (FST). Both drugs enhanced GluA1 S845 phosphorylation and potentiated Schaffer collateral-CA1 synaptic transmission. However, ketamine but not memantine elevated the expression of GluA1. Incubating acutely prepared hippocampal slices with ketamine but not memantine enhanced mTOR phosphorylation in a time course parallel to the time course of GluA1 elevation. Our results suggest that distinct properties in regulation of mTOR phosphorylation and synaptic protein expression may underlie the differential effectiveness of ketamine and memantine in their antidepressant responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Rubrocerebellar Feedback Loop Isolates the Interposed Nucleus as an Independent Processor of Corollary Discharge Information in Mice

PubMed Central

Beitzel, Christy S.; Houck, Brenda D.; Lewis, Samantha M.

2017-01-01

Understanding cerebellar contributions to motor coordination requires deeper insight into how the output structures of the cerebellum, the cerebellar nuclei, integrate their inputs and influence downstream motor pathways. The magnocellular red nucleus (RNm), a brainstem premotor structure, is a major target of the interposed nucleus (IN), and has also been described in previous studies to send feedback collaterals to the cerebellum. Because such a pathway is in a key position to provide motor efferent information to the cerebellum, satisfying predictions about the use of corollary discharge in cerebellar computations, we studied it in mice of both sexes. Using anterograde viral tracing, we show that innervation of cerebellum by rubrospinal neuron collaterals is remarkably selective for the IN compared with the cerebellar cortex. Optogenetic activation of the pathway in acute mouse brain slices drove IN activity despite small amplitude synaptic currents, suggesting an active role in IN information processing. Monosynaptic transsynaptic rabies tracing indicated the pathway contacts multiple cell types within the IN. By contrast, IN inputs to the RNm targeted a region that lacked inhibitory neurons. Optogenetic drive of IN inputs to the RNm revealed strong, direct excitation but no inhibition of RNm neurons. Together, these data indicate that the cerebellar nuclei are under afferent control independent of the cerebellar cortex, potentially diversifying its roles in motor control. SIGNIFICANCE STATEMENT The common assumption that all cerebellar mossy fibers uniformly collateralize to the cerebellar nuclei and cortex underlies classic models of convergent Purkinje influence on cerebellar output. Specifically, mossy fibers are thought to both directly excite nuclear neurons and drive polysynaptic feedforward inhibition via Purkinje neurons, setting up a fundamental computational unit. Here we present data that challenge this rule. A dedicated cerebellar nuclear afferent comprised of feedback collaterals from premotor rubrospinal neurons can directly modulate IN output independent of Purkinje cell modulation. In contrast to the IN-RNm pathway, the RNm-IN feedback pathway targets multiple cell types, potentially influencing both motor output pathways and nucleo-olivary feedback. PMID:28916520

Rubrocerebellar Feedback Loop Isolates the Interposed Nucleus as an Independent Processor of Corollary Discharge Information in Mice.

PubMed

Beitzel, Christy S; Houck, Brenda D; Lewis, Samantha M; Person, Abigail L

2017-10-18

Understanding cerebellar contributions to motor coordination requires deeper insight into how the output structures of the cerebellum, the cerebellar nuclei, integrate their inputs and influence downstream motor pathways. The magnocellular red nucleus (RNm), a brainstem premotor structure, is a major target of the interposed nucleus (IN), and has also been described in previous studies to send feedback collaterals to the cerebellum. Because such a pathway is in a key position to provide motor efferent information to the cerebellum, satisfying predictions about the use of corollary discharge in cerebellar computations, we studied it in mice of both sexes. Using anterograde viral tracing, we show that innervation of cerebellum by rubrospinal neuron collaterals is remarkably selective for the IN compared with the cerebellar cortex. Optogenetic activation of the pathway in acute mouse brain slices drove IN activity despite small amplitude synaptic currents, suggesting an active role in IN information processing. Monosynaptic transsynaptic rabies tracing indicated the pathway contacts multiple cell types within the IN. By contrast, IN inputs to the RNm targeted a region that lacked inhibitory neurons. Optogenetic drive of IN inputs to the RNm revealed strong, direct excitation but no inhibition of RNm neurons. Together, these data indicate that the cerebellar nuclei are under afferent control independent of the cerebellar cortex, potentially diversifying its roles in motor control. SIGNIFICANCE STATEMENT The common assumption that all cerebellar mossy fibers uniformly collateralize to the cerebellar nuclei and cortex underlies classic models of convergent Purkinje influence on cerebellar output. Specifically, mossy fibers are thought to both directly excite nuclear neurons and drive polysynaptic feedforward inhibition via Purkinje neurons, setting up a fundamental computational unit. Here we present data that challenge this rule. A dedicated cerebellar nuclear afferent comprised of feedback collaterals from premotor rubrospinal neurons can directly modulate IN output independent of Purkinje cell modulation. In contrast to the IN-RNm pathway, the RNm-IN feedback pathway targets multiple cell types, potentially influencing both motor output pathways and nucleo-olivary feedback. Copyright © 2017 the authors 0270-6474/17/3710085-12$15.00/0.

Experimental study of hemodynamics in the circle of willis

PubMed Central

2015-01-01

Background The Circle of Willis (CoW) is an important collateral pathway of the cerebral blood flow. An experimental study of the cerebral blood flow (CBF) distribution in different anatomical variations may help to a better understanding of the collateral mechanism of the CoW. Methods An in-vitro test rig was developed to simulate the physiological cerebral blood flow in the CoW. Ten anatomical variations were considered in this study, include a set of different degrees of stenosis in L-ICA and L-ICA occlusion coexist with common anatomical variations. Volume flow rates of efferent arteries and pressure signals at the end of communicating arteries of each case were recorded. Physiological pressure waveforms were applied as inlet boundary condition. Results In the development of L-ICA stenosis, the total CBF decreases with the increase of stenosis degree. The blood supply of ipsilateral middle cerebral artery (MCA) was affected most by the stenosis of L-ICA. Anterior communicating artery (ACoA) and ipsilateral posterior communicating artery (PCoA) function as important collateral pathways of cerebral collateral circulation when unilateral stenosis occurred. The blood supply of anterior cerebral circulation was compensated by the posterior cerebral circulation through ipsilateral PCoA when L-ICA stenosis degree is greater than 40% and the affected side was compensated immediately by the unaffected side through ACoA. Blood flow of the anterior circulation and the total CBF reached the minimum among all cases studied when L-ICA occlusion coexist with the absence of PCoA. Conclusion The results demonstrated the flow distribution patterns of the CoW under anatomical variations and clarified the collateral mechanism of the CoW. The flow ACoA is the most sensitive indexes to the morphology change of ipsilateral ICA. The relative independence of the circulation in anterior and posterior sections of the CoW is not broken and the function of ipsilateral PCoA is not activated until a severe stenosis of unilateral ICA occurs. PCoA is the most important collateral pathway of the collateral circulation and the missing of PCoA has the highest risk of stroke when the ipsilateral ICA has severe stenosis. These findings may provide the basis for future therapeutic and diagnosis applications. PMID:25603138

A protocol for characterizing the impact of collateral flow after distal middle cerebral artery occlusion

PubMed Central

DeFazio, R. Anthony; Levy, Sean; Morales, Carmen L.; Levy, Rebecca V.; Dave, Kunjan R.; Lin, Hung W.; Abaffy, Tatjana; Watson, Brant D.; Perez-Pinzon, Miguel A.; Ohanna, Victoria

2010-01-01

I. SUMMARY In humans and in animal models of stroke, collateral blood flow between territories of the major pial arteries has a profound impact on cortical infarct size. However, there is a gap in our understanding of the genetic determinants of collateral formation and flow, as well as the signaling pathways and neurovascular interactions regulating this flow. Previous studies have demonstrated that collateral flow between branches of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) can protect mouse cortex from infarction after middle cerebral artery occlusion. Because the number and diameter of collaterals varies among mouse strains and after transgenic manipulations, a combination of methods is required to control for these variations. Here, we report an inexpensive approach to characterizing the cerebrovascular anatomy, and in vivo monitoring of cerebral blood flow as well. Further, we introduce a new, minimally invasive method for the occlusion of distal MCA branches. These methods will permit a new generation of studies on the mechanisms regulating collateral remodeling and cortical blood flow after stroke. PMID:21593993

[Observation and analysis on the meridian-collateral running track-related anatomical structure in the human body].

PubMed

Xie, Hao-ran; Li, Fang-chun; Zhang, Wei-bo

2009-06-01

In the present paper the authors analyze the anatomical structure of the meridian running track by using the dialectical thought and comprehensive analysis of the integrated Chinese and western medicine. It has been observed that the "Qi-passages" of the 14 meridians of Chinese medicine are located in the connective tissue among the interspace of the muscles, etc. distributing longitudinally. The "Qi-passages" of the 15 Luomai (collaterals of the meridians) are located in the connective tissue among the interspace of the muscles, etc. distributing transversally, while those of the small branches of the meridian collaterals are located in the interspace mesenchyme of the muscle bundles distributing in the whole body. The "Qi-passages" of the tiny branches of the meridian collaterals are located in the mesenchyme of the intracellular space, such as the muscle fibers in the whole body. The authors hold that the so-called "Mai Qi" of the meridian-collaterals is the liquid-Qi flowing in the vertical and horizontal tissue interspaces. The "Qi-passage" of the meridian-collaterals of Chinese medicine is the pathway of the liquid-Qi of the tissue interspaces. The structure of the meridian-collaterals is the tissue interspace. The meridian-collateral system is a regulation-control system in the human body where the Qi-passages communicate with each other, and is, in fact, the protoplasm, the liquid-Qi circulating in the tissue interspaces.

Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

PubMed Central

Rocic, Petra

2012-01-01

Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811

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

Duncan, I.C., E-mail: docdunc@iafrica.com; Santos, C. Dos

A patient with intractable posterior epistaxis was treated with embolization of the ipsilateral sphenopalatine and facial arteries and contralateral sphenopalatine artery. She continued to bleed despite a seemingly adequate embolization procedure. A second angiogram revealed a significant collateral blood supply to the posterior nasal cavity from the accessory meningeal artery not identified during the first procedure. This was then embolized with no further epistaxis encountered. This case demonstrates yet another collateral arterial pathway that might account for a failed embolization.

A New Soluble Gelatin Sponge for Transcatheter Hepatic Arterial Embolization

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

Takasaka, Isao; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp

2010-12-15

To prepare a soluble gelatin sponge (GS) and to explore the GS particles (GSPs) that inhibit development of collateral pathways when transcatheter hepatic arterial embolization is performed. The approval of the Institutional Committee on Research Animal Care of our institution was obtained. By means of 50 and 100 kDa of regenerative medicine-gelatin (RM-G), RM-G sponges were prepared by freeze-drying and heating to temperatures of 110-150{sup o}C for cross-linkage. The soluble times of RM-GSPs were measured in vitro. Eight swine for transcatheter hepatic arterial embolization were assigned into two groups: six received 135{sup o}C/50RM-GSPs, 125{sup o}C/100RM-GSPs, and 138{sup o}C/50RM-GSPs, with solublemore » time of 48 h or more in vitro; two swine received Gelpart GSPs (G-GSPs) with insoluble time of 14 days as a control. Transarterial chemoembolization was performed on two branches of the hepatic artery per swine. RM-GSPs heated at temperatures of 110-138{sup o}C were soluble. Mean soluble times of the RM-GSPs increased with higher temperature. Hepatic branches embolized with G-GSP remained occluded after 6 days, and development of collateral pathways was observed after 3 days. Hepatic branches embolized with 135{sup o}C/50RM-GSP and 125{sup o}C/100RM-GSP remained occluded for 4 h, and recanalization was observed after 1 day. Hepatic branches embolized with 138{sup o}C/50RM-GS remained occluded for 1 day, and recanalization was observed after 2 days with no development of collateral pathways. In RM-GSs with various soluble times that were prepared by modulating the heating temperature, 138{sup o}C/50RM-GSP was the soluble GSP with the longest occlusion time without inducing development of collateral pathways.« less

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

PubMed Central

Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

PubMed

Chittajallu, R; Wester, J C; Craig, M T; Barksdale, E; Yuan, X Q; Akgül, G; Fang, C; Collins, D; Hunt, S; Pelkey, K A; McBain, C J

2017-07-28

Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

Presynaptic muscarinic control of glutamatergic synaptic transmission.

PubMed

Buño, W; Cabezas, C; Fernández de Sevilla, D

2006-01-01

The hippocampus receives cholinergic projections from the medial septal nucleus and Broca's diagonal band that terminate in the CA1, CA3, and dentate gyrus regions (Frotscher and Leranth, 1985). Glutamatergic synapses between CA3 and CA1 pyramidal neurons are presynaptically inhibited by acetylcholine (ACh), via activation of muscarinic ACh receptors (mAChRs) at the terminals of Schaffer collaterals (SCs) (Hounsgaard, 1978; Fernández de Sevilla et al., 2002, 2003). There are two types of SC-CA1 pyramidal neuron synapses. One type, called functional synapse, shows postsynaptic alpha- amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor mediated currents at resting potential (Vm) and both AMPA and N-methyl-D-aspartate receptor (NMDAR)-mediated currents when depolarized. The other type, termed silent synapse, only displays postsynaptic NMDAR-mediated currents at depolarized Vms, but does not respond at the resting Vm (Isaac et al., 1995). Using hippocampal slices obtained from young Wistar rats, we examined the effects of activation of cholinergic afferents at the stratum oriens/alveus on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of SCs. We also tested the action of the nonhydrolyzable cholinergic agonist carbamylcholine chloride (CCh) on EPSCs evoked by minimal stimulation of SCs (which activates a single or very few synapses) in functional and silent synapses.

Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

PubMed Central

Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

2015-01-01

Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals. PMID:26949505

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

PubMed

Sandler, Roman A; Fetterhoff, Dustin; Hampson, Robert E; Deadwyler, Sam A; Marmarelis, Vasilis Z

2017-07-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3

PubMed Central

Fetterhoff, Dustin; Hampson, Robert E.; Deadwyler, Sam A.; Marmarelis, Vasilis Z.

2017-01-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs. PMID:28686594

SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

PubMed

Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

2016-01-01

Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International Society for Neurochemistry.

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

PubMed

Bavley, Charlotte C; Rice, Richard C; Fischer, Delaney K; Fakira, Amanda K; Byrne, Maureen; Kosovsky, Maria; Rizzo, Bryant K; Del Prete, Dolores; Alaedini, Armin; Morón, Jose A; Higgins, Joseph J; D'Adamio, Luciano; Rajadhyaksha, Anjali M

2018-03-14

A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses. We further show that Crbn is robustly expressed in the mouse hippocampus and Crbn KO mice exhibit hyperphosphorylated levels of AMPKα (Thr172). Examination of processes downstream of AMP-activated protein kinase (AMPK) finds that Crbn KO mice have a selective impairment in mediators of the mTORC1 translation initiation pathway in parallel with lower protein levels of postsynaptic density glutamatergic proteins and higher levels of excitatory presynaptic markers in the hippocampus with no change in markers of the unfolded protein response or autophagy pathways. Acute pharmacological inhibition of AMPK activity in adult Crbn KO mice rescues learning and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic glutamatergic proteins without altering excitatory presynaptic markers. Thus, this study identifies that loss of Crbn results in learning, memory, and synaptic defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1 signaling, and decreased glutamatergic synaptic proteins. Thus, Crbn KO mice serve as an ideal model of intellectual disability to further explore molecular mechanisms of learning and memory. SIGNIFICANCE STATEMENT Intellectual disability (ID) is one of the most common neurodevelopmental disorders. The cereblon ( CRBN ) gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an intelligence quotient between 50 and 70 but devoid of other phenotypic features, making cereblon an ideal protein for the study of the fundamental aspects of learning and memory. Here, using the cereblon knock-out mouse model, we show that cereblon deficiency disrupts learning, memory, and synaptic function via AMP-activated protein kinase hyperactivity, downregulation of mTORC1, and dysregulation of excitatory synapses, with no changes in social or repetitive behaviors, consistent with findings in the human population. This establishes the cereblon knock-out mouse as a model of pure ID without the confounding behavioral phenotypes associated with other current models of ID. Copyright © 2018 the authors 0270-6474/18/382781-16$15.00/0.

[Study on the law of circulation of meridians].

PubMed

Wang, Hong-mo

2005-03-01

To study the basic law of circulation of channels and collaterals. Inherit and develop ripe experiences of predecessors based on The Yellow Emperor's Internal Classic and other classic medical books. Circulation of channels and collaterals has the eight laws, including naming law, distribution law, converging law, exterior-interior association law, beginning-ending running law, meridian-qi bidirectional circulation law, zang- and fu-organ pathway liaison law, and liaison law of connecting with trunks and sense organs.

Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BKCa channels in collateral-dependent porcine coronary arterioles

PubMed Central

Xie, Wei; Parker, Janet L.; Heaps, Cristine L.

2012-01-01

Objective Test the hypothesis that exercise training increases the contribution of large-conductance, Ca2+-dependent K+ (BKCa) channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2. Methods An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 wk) regimens. Results Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BKCa-channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+ currents (i.e., BKCa-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. Conclusions These data provide evidence that BKCa-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BKCa-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BKCa channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H2O2 as the mediator. PMID:23002811

Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe3 O4 Nanoparticle-based MR Imaging Probe.

PubMed

Wang, Ting; Hou, Yi; Bu, Bo; Wang, Wenxin; Ma, Tiancong; Liu, Chunyan; Lin, Lan; Ma, Lin; Lou, Xin; Gao, Mingyuan

2018-04-17

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α v β 3 -specific Fe 3 O 4 -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe 3 O 4 -RGD nanoprobe and the Fe 3 O 4 mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe 3 O 4 -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion.

PubMed

Ishikawa, Mami; Sugawara, Hitoshi; Nagai, Mutsumi; Kusaka, Gen; Tanaka, Yuichi; Naritaka, Heiji

2017-01-01

When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO. © 2016 S. Karger AG, Basel.

The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory.

PubMed

Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine

2015-10-29

Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.

Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool.

PubMed

Haglerød, C; Hussain, S; Nakamura, Y; Xia, J; Haug, F-M S; Ottersen, O P; Henley, J M; Davanger, S

2017-03-06

Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus. Furthermore, we show that GluA2 and protein interacting with C kinase 1 (PICK1) are colocalized at presynaptic vesicles. Similar to postsynaptic mechanisms, overexpression of either PICK1 or pep2m, which inhibit the N-ethylmaleimide sensitive fusion protein (NSF)-GluA2 interaction, decreases the concentration of GluA2 in the presynaptic active zone membrane. These data suggest that the interacting proteins PICK1 and NSF act as regulators of presynaptic GluA2-containing AMPAR trafficking between the active zone and a vesicle pool that may provide the basis of presynaptic components of synaptic plasticity. Copyright © 2017 IBRO. All rights reserved.

Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region.

PubMed

Grassi, S; Tozzi, A; Costa, C; Tantucci, M; Colcelli, E; Scarduzio, M; Calabresi, P; Pettorossi, V E

2011-09-29

In the hippocampal formation many neuromodulators are possibly implied in the synaptic plasticity such as the long-term potentiation (LTP) induced by high-frequency stimulation (HFS) of afferent fibers. We investigated the involvement of locally synthesized neural 17β-estradiol (nE(2)) in the induction of HFS-LTP in hippocampal slices from male rats by stimulating the Schaffer collateral fibers and recording the evoked field excitatory postsynaptic potential (fEPSP) in the CA1 region. We demonstrated that either the blockade of nE(2) synthesis by the aromatase inhibitor letrozole, or the antagonism of E(2) receptors (ERs) by ICI 182,780 did not prevent the induction of HFS-LTP, but reduced its amplitude by ∼60%, without influencing its maintenance. Moreover, letrozole and ICI 182,780 did not affect the first short-term post-tetanic component of LTP and the paired-pulse facilitation (PPF). These findings demonstrate that nE(2) plays an important role in the induction phase of HFS-dependent LTP. Since the basal responses were not affected by the blocking agents, we suggest that the synthesis of nE(2) is induced or enhanced by HFS through aromatase activation. In this context, the local production of nE(2) seems to be a very effective mechanism to modulate the amplitude of LTP. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic stress induces a selective decrease in AMPA receptor-mediated synaptic excitation at hippocampal temporoammonic-CA1 synapses.

PubMed

Kallarackal, Angy J; Kvarta, Mark D; Cammarata, Erin; Jaberi, Leelah; Cai, Xiang; Bailey, Aileen M; Thompson, Scott M

2013-10-02

Chronic stress promotes depression, but how it disrupts cognition and mood remains unknown. Chronic stress causes atrophy of pyramidal cell dendrites in the hippocampus and cortex in human and animal models, and a depressive-like behavioral state. We now test the hypothesis that excitatory temporoammonic (TA) synapses in the distal dendrites of CA1 pyramidal cells in rats are altered by chronic unpredictable stress (CUS) and restored by chronic antidepressant treatment, in conjunction with the behavioral consequences of CUS. We observed a decrease in AMPAR-mediated excitation at TA-CA1 synapses, but not Schaffer collateral-CA1 synapses, after CUS, with a corresponding layer-specific decrease in GluA1 expression. Both changes were reversed by chronic fluoxetine. CUS also disrupted long-term memory consolidation in the Morris water maze, a function of TA-CA1 synapses. The decreases in TA-CA1 AMPAR-mediated excitation and performance in the consolidation test were correlated positively with decreases in sucrose preference, a measure of anhedonia. We conclude that chronic stress selectively decreases AMPAR number and function at specific synapses and suggest that this underlies various depressive endophenotypes. Our findings provide evidence that glutamatergic dysfunction is an underlying cause of depression and that current first-line antidepressant drugs act by restoring excitatory synaptic strength. Our findings suggest novel therapeutic targets for this debilitating disease.

The Role of Collateral Paths in Long-Range Diffusion of 3He in Lungs

PubMed Central

Conradi, Mark S.; Yablonskiy, Dmitriy A.; Woods, Jason C.; Gierada, David S.; Bartel, Seth-Emil T.; Haywood, Susan E.; Menard, Christopher

2008-01-01

Rationale and Objectives The hyperpolarized 3He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections. Materials and Methods Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs. Results The simulations predict LRDC values of order 0.001 cm2/s, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved 3He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC. Conclusion It is proposed that LRDC in healthy lungs is determined by small collateral pathways. PMID:18486004

GPR30 activation improves memory and facilitates DHPG-induced LTD in the hippocampal CA3 of middle-aged mice.

PubMed

Xu, Wen; Cao, Jian; Zhou, Yan; Wang, Lina; Zhu, Guoqi

2018-03-01

Reduced estrogen levels and decreased expression of related receptors are typical cerebral features of aging. The G protein-coupled estrogen receptor 1 (GPER1, also known as GPR30) is considered a novel therapeutic target for neurodegenerative diseases. In this study, we demonstrated that hippocampal GPR30 expression was reduced in middle-aged mice compared with young adult mice. GPR30 agonist G1 improved both fear and spatial memory in both male and female middle-aged mice, but not in young adult mice, which were blocked by the GPR30 antagonist G15. Interestingly, a group I metabotropic glutamate receptor (mGluR) agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced long-term depression (LTD) in mossy fiber-cornu ammonis 3 (MF-CA3) synapses but not Schaffer collateral-CA1 (SC-CA1) synapses was facilitated in brain slices from G1-treated middle-aged mice. Long-term potentiation (LTP) in SC-CA1 synapses was not affected in slices from G1-treated mice. The effects of GPR30 activation on memory and DHPG-LTD in MF-CA3 synapses were further confirmed by viral expression of GPR30 in the CA3. The regulation of hippocampal synaptic plasticity by G1 treatment might be related to brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling, as G15 also blocked G1-induced activation of the BDNF-TrkB pathway. Moreover, we found that DHPG triggered GluA internalization in slices from G1-treated mice but not control mice. Pharmacological experiments showed that G1-mediated facilitation of DHPG-induced LTD in MF-CA3 synapses was dependent on protein kinase B (Akt), mammalian target of rapamycin (mTor), and TrkB signaling. In conclusion, our results indicate that GPR30 activation improves memory in middle-aged mice, likely through facilitating synaptic plasticity in the CA3. This study provides novel evidence that GPR30 activation can improve memory in middle-aged animals. Copyright © 2018 Elsevier Inc. All rights reserved.

Hepatic arteriovenous fistulae and portal vein hypoplasia in a Labrador retriever.

PubMed

Schaeffer, I G; Kirpensteijn, J; Wolvekamp, W T; Van den Ingh, T S; Rothuizen, J

2001-03-01

An 18-month-old male Labrador retriever was referred for investigation of chronic intermittent diarrhoea and vomiting of two months duration. A diagnosis of hepatic arteriovenous fistulae was made. These are extremely rare hepatic vascular anomalies which confer arterial pressure to the portal vein. Liver atrophy, portal vein hypoplasia, portal hypertension and multiple acquired portosystemic collateral vessels are the main complications. Surgical excision is a challenge as resection of large lesions may be associated with significant blood loss. In this dog, persistence of portal vein hypoplasia and extensive collateral pathways following surgery led to a reserved prognosis.

Pattern of Venous Collateral Development after Splenic Vein Occlusion in an Extended Whipple Procedure (Whipple at the Splenic Artery) and Long-Term Results.

PubMed

Rosado, Ismael Dominguez; Bhalla, Sanjeev; Sanchez, Luis A; Fields, Ryan C; Hawkins, William G; Strasberg, Steven M

2017-03-01

Extended Whipple procedures may require division of the splenic vein (SV). Controversy exists regarding the risk of sequelae of sinistral portal hypertension when the SV is ligated without reimplantation. The aim of this study was to identify postoperative venous collateral patterns and sequelae of SV ligation, as well as long-term results in an extended Whipple procedure. Patients who had an extended Whipple procedure (Whipple at the Splenic Artery or WATSA) were entered in an institutional database. Evaluation of the venous collaterals was performed at least 5 months postoperatively by imaging. Spleen size and platelet counts were measured before and after operation. Fifteen patients were entered from 2009 to 2014. SV was not reconstructed and the IMV-SV junction was always resected. Two collateral routes developed. An inferior route was present 14/15 patients. It connected the residual SV to the SMV via intermediate collateral veins in the omentum and along the colon. A superior route, present in 10/15 patients connected the residual SV to the portal vein via gastric, perigastric, and coronary veins. Gastrointestinal bleeding did not occur. Mean platelet count and spleen size were not affected significantly. Procedures were long, but few severe complications developed. In 12 patients with adenocarcinoma, the median survival has not been reached. Patients who have SV ligation in an extended Whipple are protected against sequelae of sinestral portal hypertension by inferior collateral routes. The omentum and marginal veins of the colon are key links in this pathway.

VGLUT1 or VGLUT2 mRNA-positive neurons in spinal trigeminal nucleus provide collateral projections to both the thalamus and the parabrachial nucleus in rats.

PubMed

Zhang, Chun-Kui; Li, Zhi-Hong; Qiao, Yu; Zhang, Ting; Lu, Ya-Cheng; Chen, Tao; Dong, Yu-Lin; Li, Yun-Qing; Li, Jin-Lian

2018-04-12

The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are strongly implicated in the sensory-discriminative and affective/emotional aspects of orofacial pain, respectively. These T-T and T-P projection fibers originate from the spinal trigeminal nucleus (Vsp). We previously determined that many vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were distributed in the Vsp of the adult rat, and most of these neurons sent their axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA-positive projection neurons exist that send their axons to both the thalamus and the parabrachial nucleus (PBN) has not been reported. Thus, in the present study, dual retrograde tract tracing was used in combination with fluorescence in situ hybridization (FISH) for VGLUT1 or VGLUT2 mRNA to identify the existence of VGLUT1 or VGLUT2 mRNA neurons that send collateral projections to both the thalamus and the PBN. Neurons in the Vsp that send collateral projections to both the thalamus and the PBN were mainly VGLUT2 mRNA-positive, with a proportion of 90.3%, 93.0% and 85.4% in the oral (Vo), interpolar (Vi) and caudal (Vc) subnucleus of the Vsp, respectively. Moreover, approximately 34.0% of the collateral projection neurons in the Vc showed Fos immunopositivity after injection of formalin into the lip, and parts of calcitonin gene-related peptide (CGRP)-immunopositive axonal varicosities were in direct contact with the Vc collateral projection neurons. These results indicate that most collateral projection neurons in the Vsp, particularly in the Vc, which express mainly VGLUT2, may relay orofacial nociceptive information directly to the thalamus and PBN via axon collaterals.

Cell Type-specific Intrinsic Perithreshold Oscillations in Hippocampal GABAergic Interneurons.

PubMed

Kang, Young-Jin; Lewis, Hannah Elisabeth Smashey; Young, Mason William; Govindaiah, Gubbi; Greenfield, Lazar John; Garcia-Rill, Edgar; Lee, Sang-Hun

2018-04-15

The hippocampus plays a critical role in learning, memory, and spatial processing through coordinated network activity including theta and gamma oscillations. Recent evidence suggests that hippocampal subregions (e.g., CA1) can generate these oscillations at the network level, at least in part, through GABAergic interneurons. However, it is unclear whether specific GABAergic interneurons generate intrinsic theta and/or gamma oscillations at the single-cell level. Since major types of CA1 interneurons (i.e., parvalbumin-positive basket cells (PVBCs), cannabinoid type 1 receptor-positive basket cells (CB 1 BCs), Schaffer collateral-associated cells (SCAs), neurogliaform cells and ivy cells) are thought to play key roles in network theta and gamma oscillations in the hippocampus, we tested the hypothesis that these cells generate intrinsic perithreshold oscillations at the single-cell level. We performed whole-cell patch-clamp recordings from GABAergic interneurons in the CA1 region of the mouse hippocampus in the presence of synaptic blockers to identify intrinsic perithreshold membrane potential oscillations. The majority of PVBCs (83%), but not the other interneuron subtypes, produced intrinsic perithreshold gamma oscillations if the membrane potential remained above -45 mV. In contrast, CB 1 BCs, SCAs, neurogliaform cells, ivy cells, and the remaining PVBCs (17%) produced intrinsic theta, but not gamma, oscillations. These oscillations were prevented by blockers of persistent sodium current. These data demonstrate that the major types of hippocampal interneurons produce distinct frequency bands of intrinsic perithreshold membrane oscillations. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Sub-micron opto-chemical probes for studying living neurons

NASA Astrophysics Data System (ADS)

Hossein-Zadeh, M.; Delgado, J.; Schweizer, F.; Lieberman, R.

2017-02-01

We have fabricated sub-micron opto-chemical probes for pH, oxygen and calcium monitoring and demonstrated their application in intracellular and extracellular monitoring of neurons (cortical neuronal cultures and acute hippocampal slices). Using these probes, we have measured extracellular pH in the stratum radiatum of the CA1 region of mouse hippocampus upon stimulation of presynaptic Schaffer collateral axons. Synaptic transmission was monitored using standard electrophysiological techniques. We find that the local pH transiently changes in response to synaptic stimulation. In addition, the geometry of the functionalized region on the probe combined with high sensitivity imaging enables simultaneous monitoring of spatially adjacent but distinct compartments. As proof of concept we impaled cultured neurons with the probe measured calcium and pH inside as well as directly outside of neurons as we changed the pH and calcium concentration in the physiological solution in the perfusion chamber. As such these probes can be used to study the impact of the environment on both cellular and extra-cellular space. Additionally as the chemical properties of the surrounding medium can be controlled and monitored with high precision, these probes enable differential measurement of the target parameter referenced to a stable bath. This approach eliminates the uncertainties associated with non-chemical fluctuations in the fluorescent emission and result in a self-calibrated opto-chemical probe. We have also demonstrated multifunctional probes that are capable of measuring up to three parameters in the extracellular space in brain slices.

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

PubMed

Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

PubMed

Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S

2016-10-01

Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment.

PubMed

Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Hinchey, Paul; Kollaros, Maria; Gertner, Michael J; Woo, Newton H; Tranfaglia, Michael R; Bear, Mark F; Zukin, R Suzanne; McDonald, Thomas V; Jongens, Thomas A; McBride, Sean M J

2011-03-22

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome. Copyright © 2010 Elsevier B.V. All rights reserved.

The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats.

PubMed

Sadeghi, Malihe; Reisi, Parham; Radahmadi, Maryam

2017-12-01

Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long-term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity. Stress impaired spatial memory significantly ( P <0.01). CCK in the control rats improved memory ( P <0.05), and prevented the impairments in the stress group. With respect to the control group, both fEPSP amplitude and slope were significantly ( P <0.05) decreased in the stress group. However, there were no differences between responses of the control-CCK and Stress-CCK groups compared to the control group. The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

Projections from the dorsal and ventral cochlear nuclei to the medial geniculate body.

PubMed

Schofield, Brett R; Motts, Susan D; Mellott, Jeffrey G; Foster, Nichole L

2014-01-01

Direct projections from the cochlear nucleus (CN) to the medial geniculate body (MG) mediate a high-speed transfer of acoustic information to the auditory thalamus. Anderson etal. (2006) used anterograde tracers to label the projection from the dorsal CN (DCN) to the MG in guinea pigs. We examined this pathway with retrograde tracers. The results confirm a pathway from the DCN, originating primarily from the deep layers. Labeled cells included a few giant cells and a larger number of small cells of unknown type. Many more labeled cells were present in the ventral CN (VCN). These cells, identifiable as multipolar (stellate) or small cells, were found throughout much of the VCN. Most of the labeled cells were located contralateral to the injection site. The CN to MG pathway bypasses the inferior colliculus (IC), where most ascending auditory information is processed. Anderson etal. (2006) hypothesized that CN-MG axons are collaterals of axons that reach the IC. We tested this hypothesis by injecting different fluorescent tracers into the MG and IC and examining the CN for double-labeled cells. After injections on the same side of the brain, double-labeled cells were found in the contralateral VCN and DCN. Most double-labeled cells were in the VCN, where they accounted for up to 37% of the cells labeled by the MG injection. We conclude that projections from the CN to the MG originate from the VCN and, less so, from the DCN. A significant proportion of the cells send a collateral projection to the IC. Presumably, the collateral projections send the same information to both the MG and the IC. The results suggest that T-stellate cells of the VCN are a major source of direct projections to the auditory thalamus.

Portal hypertension: a review of portosystemic collateral pathways and endovascular interventions.

PubMed

Pillai, A K; Andring, B; Patel, A; Trimmer, C; Kalva, S P

2015-10-01

The portal vein is formed at the confluence of the splenic and superior mesenteric vein behind the head of the pancreas. Normal blood pressure within the portal system varies between 5 and 10 mmHg. Portal hypertension is defined when the gradient between the portal and systemic venous blood pressure exceeds 5 mmHg. The most common cause of portal hypertension is cirrhosis. In cirrhosis, portal hypertension develops due to extensive fibrosis within the liver parenchyma causing increased vascular resistance. In addition, the inability of the liver to metabolise certain vasodilators leads to hyperdynamic splanchnic circulation resulting in increased portal blood flow. Decompression of the portal pressure is achieved by formation of portosystemic collaterals. In this review, we will discuss the pathophysiology, anatomy, and imaging findings of spontaneous portosystemic collaterals and clinical manifestations of portal hypertension with emphasis on the role of interventional radiology in the management of complications related to portal hypertension. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.

PubMed

Pivetta, Chiara; Esposito, Maria Soledad; Sigrist, Markus; Arber, Silvia

2014-01-30

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. Copyright © 2014 Elsevier Inc. All rights reserved.

Apelin signaling modulates splanchnic angiogenesis and portosystemic collateral vessel formation in rats with portal hypertension.

PubMed

Tiani, Carolina; Garcia-Pras, Ester; Mejias, Marc; de Gottardi, Andrea; Berzigotti, Annalisa; Bosch, Jaime; Fernandez, Mercedes

2009-02-01

Angiogenesis is a pathological hallmark of portal hypertension. Although VEGF is considered to be the most important proangiogenic factor in neoangiogenesis, this process requires the coordinated action of a variety of factors. Identification of novel molecules involved in angiogenesis is highly relevant, since they may represent potential new targets to suppress pathological neovascularization in angiogenesis-related diseases like portal hypertension. The apelin/APJ signaling pathway plays a crucial role in angiogenesis. Therefore, we determined whether the apelin system modulates angiogenesis-driven processes in portal hypertension. Partial portal vein-ligated rats were treated with the APJ antagonist F13A for seven days. Splanchnic neovascularization and expression of angiogenesis mediators (Western blotting) was determined. Portosystemic collateral formation (microspheres), and hemodynamic parameters (flowmetry) were also assessed. Apelin and its receptor APJ were overexpressed in the splanchnic vasculature of portal hypertensive rats. F13A effectively decreased, by 52%, splanchnic neovascularization and expression of proangiogenic factors VEGF, PDGF and angiopoietin-2 in portal hypertensive rats. F13A also reduced, by 35%, the formation of portosystemic collateral vessels. This study provides the first experimental evidence showing that the apelin/APJ system contributes to portosystemic collateralization and splanchnic neovascularization in portal hypertensive rats, presenting a potential novel therapeutic target for portal hypertension.

Erythema multiforme

MedlinePlus

French LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 20. ...

A spontaneous pre-anastomotic occlusion does not necessarily impair forearm native dialysis fistulas: echo-Doppler, 3D MR angiographic and digital subtraction angiographic imaging.

PubMed

Verbeeck, N; Pillet, J C; Prospert, E; McLntyre, D; Lamy, S

2013-01-01

Renal transplantation is the choice treatment of end-stage renal disease. When it is not indicated or not immediately feasible, hemodialysis must be performed, preferably via a native arteriovenous fistula in the forearm. A pre-anastomotic occlusion of this type of fistula is often accompanied by a thrombosis of its draining vein. In some instances, the venous segment may remain permeable thanks to the development of arterial collateral pathways and may even allow efficient dialysis without any clinical syndrome of distal steal. We present the echo-Doppler, magnetic and angiographic characteristics of three of these collateralized shunts that have remained functional, in one of the cases following a percutaneous dilation.

Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

PubMed

Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

2015-08-20

Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the defect in neuronal-circuits of hippocampus (DG-CA4-CA1-Sub) that were significantly damaged leading to memory impairment. Interestingly, RSV was observed to culminate pathological events in the hippocampal neuronal circuit during aging, proving them as potent therapeutic drug against age-associated neurodegeneration and memory loss. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Hippocampal Ripple Oscillations and Inhibition-First Network Models: Frequency Dynamics and Response to GABA Modulators.

PubMed

Donoso, José R; Schmitz, Dietmar; Maier, Nikolaus; Kempter, Richard

2018-03-21

Hippocampal ripples are involved in memory consolidation, but the mechanisms underlying their generation remain unclear. Models relying on interneuron networks in the CA1 region disagree on the predominant source of excitation to interneurons: either "direct," via the Schaffer collaterals that provide feedforward input from CA3 to CA1, or "indirect," via the local pyramidal cells in CA1, which are embedded in a recurrent excitatory-inhibitory network. Here, we used physiologically constrained computational models of basket-cell networks to investigate how they respond to different conditions of transient, noisy excitation. We found that direct excitation of interneurons could evoke ripples (140-220 Hz) that exhibited intraripple frequency accommodation and were frequency-insensitive to GABA modulators, as previously shown in in vitro experiments. In addition, the indirect excitation of the basket-cell network enabled the expression of intraripple frequency accommodation in the fast-gamma range (90-140 Hz), as in vivo In our model, intraripple frequency accommodation results from a hysteresis phenomenon in which the frequency responds differentially to the rising and descending phases of the transient excitation. Such a phenomenon predicts a maximum oscillation frequency occurring several milliseconds before the peak of excitation. We confirmed this prediction for ripples in brain slices from male mice. These results suggest that ripple and fast-gamma episodes are produced by the same interneuron network that is recruited via different excitatory input pathways, which could be supported by the previously reported intralaminar connectivity bias between basket cells and functionally distinct subpopulations of pyramidal cells in CA1. Together, our findings unify competing inhibition-first models of rhythm generation in the hippocampus. SIGNIFICANCE STATEMENT The hippocampus is a part of the brain of humans and other mammals that is critical for the acquisition and consolidation of memories. During deep sleep and resting periods, the hippocampus generates high-frequency (∼200 Hz) oscillations called ripples, which are important for memory consolidation. The mechanisms underlying ripple generation are not well understood. A prominent hypothesis holds that the ripples are generated by local recurrent networks of inhibitory neurons. Using computational models and experiments in brain slices from rodents, we show that the dynamics of interneuron networks clarify several previously unexplained characteristics of ripple oscillations, which advances our understanding of hippocampus-dependent memory consolidation. Copyright © 2018 the authors 0270-6474/18/383125-23$15.00/0.

Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

PubMed

Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

2012-07-15

We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

PubMed Central

Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Gall, Christine M.; Lynch, Gary; Baram, Tallie Z.

2010-01-01

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF1) located on pyramidal cell dendrites. Additionally, chronic CRF1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH-expression is augmented in hippocampus of middle-aged CES rats, and then tested if the morphological defects and poor memory performance in these animals involve excessive activation of CRF1 receptors. Central or peripheral administration of a CRF1 blocker following the stress period improved memory performance of CES rats in novel object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF1 occupancy post-hoc normalized hippocampal function during middle-age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress. PMID:20881118

Short-term field stimulation mimics synaptic maturation of hippocampal synapses

PubMed Central

Bagley, Elena E; Westbrook, Gary L

2012-01-01

Many aspects of synaptic transmission are modified during development, reflecting not only the consequence of developmental programmes of gene expression, but also the effects of ongoing neural activity. We investigated the role of synaptic activity in the maturation of Schaffer collateral (SC)–CA1 synapses using sustained low frequency field stimulation of acute brain slices. Between postnatal days 4–6 and 14–16, mouse SC–CA1 synapses in naïve slices showed a developmental decrease in the probability of transmitter release (Pr) and an increase in the contribution of GluN2A (NR2A) subunits to the NMDA receptor-mediated excitatory postsynaptic current (EPSC). Surprisingly, these developmental changes could be mimicked by short term (4 h) in vitro synaptic activity in slices taken from postnatal days (PND) 4–6 mice. However, different activity levels were required to alter release probability compared to the NMDA receptor subunit composition. Spontaneous synaptic activity was sufficient to alter the NMDA receptor subunit composition, but sustained low-frequency field stimulation of the brain slice (0.1 Hz, 4 h) was necessary to reduce release probability, as assessed 1 h following the cessation of stimulation. The protein synthesis inhibitor anisomycin blocked the effect of field stimulation on release probability. These results indicate that features of mature excitatory synapses can be rapidly induced in immature neurons. The activity dependence of the Pr and NMDA receptor subunit composition serves as a sensitive indicator of prior neural activity, and provides dual mechanisms for homeostatic control of excitatory synaptic efficacy. PMID:22351628

Short-term field stimulation mimics synaptic maturation of hippocampal synapses.

PubMed

Bagley, Elena E; Westbrook, Gary L

2012-04-01

Many aspects of synaptic transmission are modified during development, reflecting not only the consequence of developmental programmes of gene expression, but also the effects of ongoing neural activity. We investigated the role of synaptic activity in the maturation of Schaffer collateral (SC)-CA1 synapses using sustained low frequency field stimulation of acute brain slices. Between postnatal days 4-6 and 14-16, mouse SC-CA1 synapses in naïve slices showed a developmental decrease in the probability of transmitter release (P(r)) and an increase in the contribution of GluN2A (NR2A) subunits to the NMDA receptor-mediated excitatory postsynaptic current (EPSC). Surprisingly, these developmental changes could be mimicked by short term (4 h) in vitro synaptic activity in slices taken from postnatal days (PND) 4-6 mice. However, different activity levels were required to alter release probability compared to the NMDA receptor subunit composition. Spontaneous synaptic activity was sufficient to alter the NMDA receptor subunit composition, but sustained low-frequency field stimulation of the brain slice (0.1 Hz, 4 h) was necessary to reduce release probability, as assessed 1 h following the cessation of stimulation. The protein synthesis inhibitor anisomycin blocked the effect of field stimulation on release probability. These results indicate that features of mature excitatory synapses can be rapidly induced in immature neurons. The activity dependence of the P(r) and NMDA receptor subunit composition serves as a sensitive indicator of prior neural activity, and provides dual mechanisms for homeostatic control of excitatory synaptic efficacy.

Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

PubMed

Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

2015-07-01

Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood. © 2014 Society for the Study of Addiction.

Circadian Regulation of Hippocampal Long-Term Potentiation

PubMed Central

Chaudhury, Dipesh; Wang, Louisa M.; Colwell, Christopher S.

2008-01-01

The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus. PMID:15851529

NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area.

PubMed

Racca, C; Stephenson, F A; Streit, P; Roberts, J D; Somogyi, P

2000-04-01

Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64-0.70] was much lower than that of the AMPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs.

Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion.

PubMed

Marosi, Máté; Fuzik, János; Nagy, Dávid; Rákos, Gabriella; Kis, Zsolt; Vécsei, László; Toldi, József; Ruban-Matuzani, Angela; Teichberg, Vivian I; Farkas, Tamás

2009-02-14

Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate. The present study had the aim of an evaluation of the effects of the blood glutamate scavenger oxaloacetate on the impaired long-term potentiation (LTP) induced in the 2-vessel occlusion ischaemic model in rat. Transient (30-min) incomplete forebrain ischaemia was produced 72 h before LTP induction. Although the short transient brain hypoperfusion did not induce histologically identifiable injuries in the CA1 region (Fluoro-Jade B, S-100 and cresyl violet), it resulted in an impaired LTP function in the hippocampal CA1 region without damaging the basal synaptic transmission between the Schaffer collaterals and the pyramidal neurons. This impairment could be fended off in a dose-dependent manner by the intravenous administration of oxaloacetate in saline (at doses between 1.5 mmol and 0.1 mumol) immediately after the transient hypoperfusion. Our results suggest that oxaloacetate-mediated blood and brain glutamate scavenging contributes to the restoration of the LTP after its impairment by brain ischaemia.

77 FR 6813 - President's National Security Telecommunications Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Schaffer, Assistant Secretary for Cybersecurity and Communications, an update on the Cloud Computing Subcommittee from Mr. Mark McLaughlin, Chair of the Cloud Computing Subcommittee, and an update on the National...

Nonnutrient Anthropogenic Chemicals in Seagrass Ecosystems: Fate and Effects

EPA Science Inventory

Literature reviews have been published for seagrass taxonomy, geographical distribution, species diversity, grazer-epiphyte interactions, morphology, physiology, salinity requirements, and nutrient impacts (Schaffer 1995; Jernakoff et al. 1996; Touchette and Burholder 2000; Borto...

Quality as a passion.

PubMed

Blair, Robin

2005-04-01

CIGNA Senior Vice President and Chief Clinical Officer W. Allen Schaffer, M.D., describes how a national health plan combines IT and human resources, and embraces national evidence-based standards, to influence the individual health status of millions of members.

Analysis of United States Air Forces Central Government Purchase Card Reachback Viability

DTIC Science & Technology

2011-12-01

being a wealth of knowledge and answering every contingency and reachback question throughout our PMA trip • Ms. Karey Schaffer – for giving us a...11. Karey L. Shaffer Program Manager, Acquisition Research Program, GB

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

PubMed Central

Dong, Yulin; Li, Jinlian; Zhang, Fuxing; Li, Yunqing

2011-01-01

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals. PMID:21980505

[Hemodynamic phenomena in retrobulhar and eyeball vessels].

PubMed

Modrzejewska, Monika

2011-01-01

The purpose of this review was to evaluate factors connected with blood flow and indices regulating vascular diameter and some parameters influencing retrobulbar circulation such as type of vascular resistance, anatomical structure of vascular wall and vessel lumen. Neurogenic and angiogenic factors, rheological blood composition, presence of anatomical and pathological obstructions on blood flow pathway as well as degree of development of collateral circulation pathways--have influence on the volume and blood flow velocity in eyeball. There were discussed bulbar circulation hemodynamics, emphasizing the importance of perfusion pressure. The role of risk factors was underlined for pathological lesions in vessels supplying blood to eyeball and in ophthalmic artery (OA) and its collaterals, in central retinal artery (CRA) as well as posterior ciliary arteries (PCAs), and in venous system carrying away blood from eye. IN CONCLUSION--the results of many studies of retrobulbar blood flow in different types of ophthalmic diseases of the vascular etiopathogenesis indicate that registry of the mean values of blood flow parameters and vascular resistance indices parallel to measurement of blood flow spectrum in OA, CRA, PCAs arteries, might contribute much information to explain or to evaluate nature of pathological changes in retinal and choroidal circulation.

A Platonic Sextet for Strings

ERIC Educational Resources Information Center

Schaffer, Karl

2012-01-01

The use of traditional string figures by the Dr. Schaffer and Mr. Stern Dance Ensemble led to experimentation with polyhedral string constructions. This article presents a series of polyhedra made with six loops of three colors which sequence through all the Platonic Solids.

A Rapid Cytoplasmic Mechanism for PI3 Kinase Regulation by the Nuclear Thyroid Hormone Receptor, TRβ, and Genetic Evidence for Its Role in the Maturation of Mouse Hippocampal Synapses In Vivo

PubMed Central

Martin, Negin P.; Fernandez de Velasco, Ezequiel Marron; Mizuno, Fengxia; Scappini, Erica L.; Gloss, Bernd; Erxleben, Christian; Williams, Jason G.; Stapleton, Heather M.; Gentile, Saverio

2014-01-01

Several rapid physiological effects of thyroid hormone on mammalian cells in vitro have been shown to be mediated by the phosphatidylinositol 3-kinase (PI3K), but the molecular mechanism of PI3K regulation by nuclear zinc finger receptor proteins for thyroid hormone and its relevance to brain development in vivo have not been elucidated. Here we show that, in the absence of hormone, the thyroid hormone receptor TRβ forms a cytoplasmic complex with the p85 subunit of PI3K and the Src family tyrosine kinase, Lyn, which depends on two canonical phosphotyrosine motifs in the second zinc finger of TRβ that are not conserved in TRα. When hormone is added, TRβ dissociates and moves to the nucleus, and phosphatidylinositol (3, 4, 5)-trisphosphate production goes up rapidly. Mutating either tyrosine to a phenylalanine prevents rapid signaling through PI3K but does not prevent the hormone-dependent transcription of genes with a thyroid hormone response element. When the rapid signaling mechanism was blocked chronically throughout development in mice by a targeted point mutation in both alleles of Thrb, circulating hormone levels, TRβ expression, and direct gene regulation by TRβ in the pituitary and liver were all unaffected. However, the mutation significantly impaired maturation and plasticity of the Schaffer collateral synapses on CA1 pyramidal neurons in the postnatal hippocampus. Thus, phosphotyrosine-dependent association of TRβ with PI3K provides a potential mechanism for integrating regulation of development and metabolism by thyroid hormone and receptor tyrosine kinases. PMID:24932806

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

PubMed Central

Meredith, Rhiannon M.; van Ooyen, Arjen

2012-01-01

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

Endocannabinoid Release Modulates Electrical Coupling between CCK Cells Connected via Chemical and Electrical Synapses in CA1

PubMed Central

Iball, Jonathan; Ali, Afia B.

2011-01-01

Electrical coupling between some subclasses of interneurons is thought to promote coordinated firing that generates rhythmic synchronous activity in cortical regions. Synaptic activity of cholecystokinin (CCK) interneurons which co-express cannabinoid type-1 (CB1) receptors are powerful modulators of network activity via the actions of endocannabinoids. We investigated the modulatory actions of endocannabinoids between chemically and electrically connected synapses of CCK cells using paired whole-cell recordings combined with biocytin and double immunofluorescence labeling in acute slices of rat hippocampus at P18–20 days. CA1 stratum radiatum CCK Schaffer collateral-associated cells were coupled electrically with each other as well as CCK basket cells and CCK cells with axonal projections expanding to dentate gyrus. Approximately 50% of electrically coupled cells received facilitating, asynchronously released inhibitory postsynaptic potential (IPSPs) that curtailed the steady-state coupling coefficient by 57%. Tonic CB1 receptor activity which reduces inhibition enhanced electrical coupling between cells that were connected via chemical and electrical synapses. Blocking CB1 receptors with antagonist, AM-251 (5 μM) resulted in the synchronized release of larger IPSPs and this enhanced inhibition further reduced the steady-state coupling coefficient by 85%. Depolarization induced suppression of inhibition (DSI), maintained the asynchronicity of IPSP latency, but reduced IPSP amplitudes by 95% and enhanced the steady-state coupling coefficient by 104% and IPSP duration by 200%. However, DSI did not did not enhance electrical coupling at purely electrical synapses. These data suggest that different morphological subclasses of CCK interneurons are interconnected via gap junctions. The synergy between the chemical and electrical coupling between CCK cells probably plays a role in activity-dependent endocannabinoid modulation of rhythmic synchronization. PMID:22125513

Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits

PubMed Central

Wahlstrom-Helgren, Sarah

2016-01-01

Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. PMID:27605532

Maturation- and sex-sensitive depression of hippocampal excitatory transmission in a rat schizophrenia model.

PubMed

Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

2016-01-01

Schizophrenia is associated with behavioral and brain structural abnormalities, of which the hippocampus appears to be one of the most consistent region affected. Previous studies performed on the poly I:C model of schizophrenia suggest that alterations in hippocampal synaptic transmission and plasticity take place in the offspring. However, these investigations yielded conflicting results and the neurophysiological alterations responsible for these deficits are still unclear. Here we performed for the first time a longitudinal study examining the impact of prenatal poly I:C treatment and of gender on hippocampal excitatory neurotransmission. In addition, we examined the potential preventive/curative effects of risperidone (RIS) treatment during the peri-adolescence period. Excitatory synaptic transmission was determined by stimulating Schaffer collaterals and monitoring fiber volley amplitude and slope of field-EPSP (fEPSP) in CA1 pyramidal neurons in male and female offspring hippocampal slices from postnatal days (PNDs) 18-20, 34, 70 and 90. Depression of hippocampal excitatory transmission appeared at juvenile age in male offspring of the poly I:C group, while it expressed with a delay in female, manifesting at adulthood. In addition, a reduced hippocampal size was found in both adult male and female offspring of poly I:C treated dams. Treatment with RIS at the peri-adolescence period fully restored in males but partly repaired in females these deficiencies. A maturation- and sex-dependent decrease in hippocampal excitatory transmission occurs in the offspring of poly I:C treated pregnant mothers. Pharmacological intervention with RIS during peri-adolescence can cure in a gender-sensitive fashion early occurring hippocampal synaptic deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

Endogenous hippocampal LTD that is enabled by spatial object recognition requires activation of NMDA receptors and the metabotropic glutamate receptor, mGlu5.

PubMed

Goh, Jinzhong Jeremy; Manahan-Vaughan, Denise

2013-02-01

Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent plasticity to afferent stimulation when coupled with a spatial learning event, whereby the afferent stimulation normally produces short-term plasticity or no change in synaptic strength if given in the absence of novel learning. Recently, it was reported that in the mouse hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse afferent stimulation is coupled with a novel spatial learning. It is not known to what extent this phenomenon shares molecular properties with synaptic plasticity that is typically induced by means of patterned electrical afferent stimulation. In previous work, we showed that a novel spatial object recognition task facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult mice, whereas reexposure to the familiar spatial configuration ∼24 h later elicited no such facilitation. Here we report that treatment with the NMDA receptor antagonist, (±)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2-methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the novel learning conditions. Behavioral assessment during re-exposure after application of the antagonists revealed that the animals did not remember the object during novel exposure and treated them as if they were novel. Under these circumstances, where the acquisition of novel spatial information was involved, LTD was facilitated. Our data support that the endogenous LTD that is enabled through novel spatial learning in adult mice is critically dependent on the activation of both the NMDA receptors and mGlu5. Copyright © 2012 Wiley Periodicals, Inc.

Effects of GABA and bicuculline on N-methyl-D-aspartate- and quisqualate-induced reductions in extracellular free calcium in area CA1 of the hippocampal slice.

PubMed

Hamon, B; Heinemann, U

1986-01-01

Decreases in extracellular free calcium ([Ca2+]o) and concomitant field potentials were recorded from the dendritic and cell body layers of the CA1 field in transverse hippocampal slices. They were elicited by tetanic stimulation of Schaffer collaterals and commissural fibers or by iontophoretic application of the excitatory amino acids N-methyl-D-aspartate (NMDA) and quisqualate (Quis). Under control conditions, decreases in [Ca2+]o were found to be maximal in stratum pyramidale (SP). In stratum radiatum (SR), 100 micron away from SP, decreases in [Ca2+]o were half the size of those observed in SP. Bicuculline methiodide, bath-applied at concentrations of 10-100 microM, enhanced the reductions in [Ca2+]o, increased the field potentials in all layers and also induced "spontaneous" epileptiform activity. In the presence of bicuculline, the decreases in [Ca2+]o were particularly enhanced in SR and were often greater than those recorded in SP. This was the case for changes in [Ca2+]o induced either by repetitive electrical stimulation or by application of NMDA and Quis. When synaptic transmission was blocked by perfusing the slices with a low Ca2+ medium, all NMDA and Quis-induced changes in [Ca2+]o were predictably reduced but there was a relative enhancement of changes in [Ca2+]o in SR with respect to those in SP. We propose that, under normal conditions, an inhibitory control mediated by GABA limits the reductions of [Ca2+]o particularly in SR. In support of this proposal, we found that bath-applied GABA had a depressant action on changes in [Ca2+]o.

The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies

PubMed Central

Senter, Rebecca K.; Ghoshal, Ayan; Walker, Adam G.; Xiang, Zixiu; Niswender, Colleen M.; Conn, P. Jeffrey

2016-01-01

Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SC-CA1) synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated to be the molecular underpinning for several cognitive functions. Deficits in LTP and LTD have been implicated in the pathophysiology of several neurological and psychiatric disorders. Therefore, there has been a large effort focused on developing an understanding of the mechanisms underlying these forms of plasticity and novel therapeutic strategies that improve or rescue these plasticity deficits. Among many other targets, the metabotropic glutamate (mGlu) receptors show promise as novel therapeutic candidates for the treatment of these disorders. Among the eight distinct mGlu receptor subtypes (mGlu1-8), the mGlu1,2,3,5,7 subtypes are expressed throughout the hippocampus and have been shown to play important roles in the regulation of synaptic plasticity in this brain area. However, development of therapeutic agents that target these mGlu receptors has been hampered by a lack of subtype-selective compounds. Recently, discovery of allosteric modulators of mGlu receptors has provided novel ligands that are highly selective for individual mGlu receptor subtypes. The mGlu receptors modulate the multiple forms of synaptic plasticity at both SC-CA1 and MF synapses and allosteric modulators of mGlu receptors have emerged as potential therapeutic agents that may rescue plasticity deficits and improve cognitive function in patients suffering from multiple neurological and psychiatric disorders. PMID:27296640

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning.

PubMed

Nanou, Evanthia; Scheuer, Todd; Catterall, William A

2016-11-15

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

PubMed

Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

2015-05-01

Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Up-regulation of GLT-1 severely impairs LTD at mossy fibre--CA3 synapses.

PubMed

Omrani, Azar; Melone, Marcello; Bellesi, Michele; Safiulina, Victoria; Aida, Tomomi; Tanaka, Kohishi; Cherubini, Enrico; Conti, Fiorenzo

2009-10-01

Glutamate transporters are responsible for clearing synaptically released glutamate from the extracellular space. By this action, they maintain low levels of ambient glutamate, thus preventing excitotoxic damage, and contribute to shaping synaptic currents. We show that up-regulation of the glutamate transporter GLT-1 by ceftriaxone severely impaired mGluR-dependent long-term depression (LTD), induced at rat mossy fibre (MF)-CA3 synapses by repetitive stimulation of afferent fibres. This effect involved GLT-1, since LTD was rescued by the selective GLT-1 antagonist dihydrokainate (DHK). DHK per se produced a modest decrease in fEPSP amplitude that rapidly regained control levels after DHK wash out. Moreover, the degree of fEPSP inhibition induced by the low-affinity glutamate receptor antagonist gamma-DGG was similar during basal synaptic transmission but not during LTD, indicating that in ceftriaxone-treated rats LTD induction did not alter synaptic glutamate transient concentration. Furthermore, ceftriaxone-induced GLT-1 up-regulation significantly reduced the magnitude of LTP at MF-CA3 synapses but not at Schaffer collateral-CA1 synapses. Postembedding immunogold studies in rats showed an increased density of gold particles coding for GLT-1a in astrocytic processes and in mossy fibre terminals; in the latter, gold particles were located near and within the active zones. In both CEF-treated and untreated GLT-1 KO mice used for verifying the specificity of immunostaining, the density of gold particles in MF terminals was comparable to background levels. The enhanced expression of GLT-1 at release sites may prevent activation of presynaptic receptors, thus revealing a novel mechanism by which GLT-1 regulates synaptic plasticity in the hippocampus.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

PubMed

Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

2017-08-01

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated

PubMed Central

Ayala, Jennifer E.; Niswender, Colleen M.; Luo, Qingwei; Banko, Jessica L.; Conn, P. Jeffrey

2008-01-01

Summary Group III metabotropic glutamate receptors (mGluRs) reduce synaptic transmission at the Schaffer collateral-CA1 (SC-CA1) synapse in rats by a presynaptic mechanism. Previous studies show that low concentrations of the group III-selective agonist, L-AP4, reduce synaptic transmission in slices from neonatal but not adult rats, whereas high micromolar concentrations reduce transmission in both age groups. L-AP4 activates mGluRs 4 and 8 at much lower concentrations than those required to activate mGluR7, suggesting that the group III mGluR subtype modulating transmission is a high affinity receptor in neonates and a low affinity receptor in adults. The previous lack of subtype selective ligands has made it difficult to test this hypothesis. We have measured fEPSPs in the presence of novel subtype selective agents to address this question. We show that the effects of L-AP4 can be blocked by LY341495 in both neonates and adults, verifying that these effects are mediated by mGluRs. In addition, the selective mGluR8 agonist, DCPG, has a significant effect in slices from neonatal rats but does not reduce synaptic transmission in adult slices. The mGluR4 selective allosteric potentiator, PHCCC, is unable to potentiate the L-AP4-induced effects at either age. Taken together, our data suggest that group III mGluRs regulate transmission at the SC-CA1 synapse throughout development but there is a developmental regulation of the subtypes involved so that that both mGluR8 serves this role in neonates but not adults whereas mGluR7 is involved in regulating transmission at this synapse in throughout postnatal development. PMID:18255102

G protein-gated K+ channel ablation in forebrain pyramidal neurons selectively impairs fear learning

PubMed Central

Victoria, Nicole C.; de Velasco, Ezequiel Marron Fernandez; Ostrovskaya, Olga; Metzger, Stefania; Xia, Zhilian; Kotecki, Lydia; Benneyworth, Michael A.; Zink, Anastasia N.; Martemyanov, Kirill A.; Wickman, Kevin

2015-01-01

Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders. PMID:26612516

Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors.

PubMed

Penn, A C; Zhang, C L; Georges, F; Royer, L; Breillat, C; Hosy, E; Petersen, J D; Humeau, Y; Choquet, D

2017-09-21

Long-term potentiation (LTP) of excitatory synaptic transmission has long been considered a cellular correlate for learning and memory. Early LTP (less than 1 h) had initially been explained either by presynaptic increases in glutamate release or by direct modification of postsynaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function. Compelling models have more recently proposed that synaptic potentiation can occur by the recruitment of additional postsynaptic AMPA receptors (AMPARs), sourced either from an intracellular reserve pool by exocytosis or from nearby extra-synaptic receptors pre-existing on the neuronal surface. However, the exact mechanism through which synapses can rapidly recruit new AMPARs during early LTP remains unknown. In particular, direct evidence for a pivotal role of AMPAR surface diffusion as a trafficking mechanism in synaptic plasticity is still lacking. Here, using AMPAR immobilization approaches, we show that interfering with AMPAR surface diffusion markedly impairs synaptic potentiation of Schaffer collaterals and commissural inputs to the CA1 area of the mouse hippocampus in cultured slices, acute slices and in vivo. Our data also identify distinct contributions of various AMPAR trafficking routes to the temporal profile of synaptic potentiation. In addition, AMPAR immobilization in vivo in the dorsal hippocampus inhibited fear conditioning, indicating that AMPAR diffusion is important for the early phase of contextual learning. Therefore, our results provide a direct demonstration that the recruitment of new receptors to synapses by surface diffusion is a critical mechanism for the expression of LTP and hippocampal learning. Since AMPAR surface diffusion is dictated by weak Brownian forces that are readily perturbed by protein-protein interactions, we anticipate that this fundamental trafficking mechanism will be a key target for modulating synaptic potentiation and learning.

Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP.

PubMed

Tang, Wannan; Szokol, Karolina; Jensen, Vidar; Enger, Rune; Trivedi, Chintan A; Hvalby, Øivind; Helm, P Johannes; Looger, Loren L; Sprengel, Rolf; Nagelhus, Erlend A

2015-02-18

To date, it has been difficult to reveal physiological Ca(2+) events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca(2+) signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca(2+) indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca(2+) signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca(2+) signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca(2+) transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca(2+) signals in processes and failed to affect the somatic Ca(2+) response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca(2+) signals that mimicked the stimulation-evoked astrocytic Ca(2+) responses. We conclude that stimulation-evoked Ca(2+) signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP. Copyright © 2015 the authors 0270-6474/15/353016-06$15.00/0.

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

Algorithms for Efficient Intelligence Collection

DTIC Science & Technology

2013-09-01

2006. Cortical substrates for exploratory decisions in humans. Nature 441(7095) 876–879. Deitchman, S. J. 1962. A lanchester model of guerrilla...Monterey, CA. Pearl, J. 1986. Fusion, propagation and structuring in belief networks. Artificial Intelligence 29 241–288. Schaffer, M. B. 1968. Lanchester

75 FR 62921 - Senior Executive Service; Legal Division Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... Law and Regulation); M.J.K. Maher, Jr., Deputy Assistant General Counsel (Enforcement & Intelligence... General Counsel; Mark Monborne, Assistant General Counsel (Enforcement & Intelligence); Clarissa C. Potter... Engraving and Printing; Laurie Schaffer, Assistant General Counsel (Banking and Finance); Daniel P. Shaver...

Extrahepatic portal obstruction without hepatopetal pathway associated with congenital arterioportal fistula: a case report.

PubMed

Maeda, N; Horie, Y; Koda, M; Suou, T; Andachi, H; Nakamura, K; Kawasaki, H

1997-01-01

Extrahepatic portal obstruction is one of the causes of portal hypertension, in which well-developed hepatopetal pathways are commonly recognized. Herein an extremely rare case of extrahepatic portal obstruction without hepatopetal pathway, probably caused by arterioportal fistula, is reported. The patient was a normally matured 16-year-old girl admitted for further evaluation of jaundice, presenting with the clinical manifestations of the portal hypertension associated with hypersplenism and portosystemic venous shunt. Celiac angiography clearly demonstrated an intrahepatic arterial aneurysm fed by the right hepatic artery shunting to the superior mesenteric vein, and portography disclosed complete obstruction of the portal trunk with conspicuous hepatofugal pathway but no hepatopetal collateral veins. The exact mechanism of this phenomenon is not known and whether the extrahepatic portal obstruction was primary or secondary is still obscure. However, this is the first case report in the world literature describing extrahepatic portal obstruction with absence of hepatopetal pathway.

Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

PubMed Central

Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Squadrito, Mario Leonardo; Finisguerra, Veronica; Deschoemaeker, Sofie; Bruyére, Françoise; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Magat, Julie; Bhattacharyya, Tapan; Anisimov, Andrey; Jordan, Benedicte F.; Alitalo, Kari; Maxwell, Patrick; Gallez, Bernard; Zhuang, Zhen W.; Saito, Yoshihiko; Simons, Michael; De Palma, Michele; Mazzone, Massimiliano

2015-01-01

PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage1–5. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion6–8. We show that Phd2 (also known as Egln1) haplodeficient (Phd2+/−) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2+/− mice was due to an expansion of tissue-resident, M2-like macrophages9,10 and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a proarteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2+/− macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders. PMID:21983962

The Effects of Collateral Consequences of Criminal Involvement on Employment, Use of Temporary Assistance for Needy Families, and Health.

PubMed

Sheely, Amanda; Kneipp, Shawn M

2015-01-01

Criminal convictions are often associated with collateral consequences that limit access to the forms of employment and social services on which disadvantaged women most frequently rely--regardless of the severity of the offense. These consequences may play an important role in perpetuating health disparities by socioeconomic status and gender. We examined the extent to which research studies to date have assessed whether a criminal conviction might influence women's health by limiting access to Temporary Assistance for Needy Families (TANF) and employment, as a secondary, or "collateral" criminal conviction-related consequence. We reviewed 434 peer-reviewed journal articles retrieved from three electronic article databases and 197 research reports from three research organizations. Two reviewers independently extracted data from each eligible article or report using a standardized coding scheme. Of the sixteen eligible studies included in the review, most were descriptive. None explored whether receiving TANF modified health outcomes, despite its potential to do so. Researchers to date have not fully examined the causal pathways that could link employment, receiving TANF, and health, especially for disadvantaged women. Future research is needed to address this gap and to understand better the potential consequences of the criminal justice system involvement on the health of this vulnerable population.

Sphingosine-1-Phosphate Receptor-1 Selective Agonist Enhances Collateral Growth and Protects against Subsequent Stroke

PubMed Central

Ichijo, Masahiko; Ishibashi, Satoru; Li, Fuying; Yui, Daishi; Miki, Kazunori; Mizusawa, Hidehiro; Yokota, Takanori

2015-01-01

Background and Purpose Collateral growth after acute occlusion of an intracranial artery is triggered by increasing shear stress in preexisting collateral pathways. Recently, sphingosine-1-phosphate receptor-1 (S1PR1) on endothelial cells was reported to be essential in sensing fluid shear stress. Here, we evaluated the expression of S1PR1 in the hypoperfused mouse brain and investigated the effect of a selective S1PR1 agonist on leptomeningeal collateral growth and subsequent ischemic damage after focal ischemia. Methods In C57Bl/6 mice (n = 133) subjected to unilateral common carotid occlusion (CCAO) and sham surgery. The first series examined the time course of collateral growth, cell proliferation, and S1PR1 expression in the leptomeningeal arteries after CCAO. The second series examined the relationship between pharmacological regulation of S1PR1 and collateral growth of leptomeningeal anastomoses. Animals were randomly assigned to one of the following groups: LtCCAO and daily intraperitoneal (ip) injection for 7 days of an S1PR1 selective agonist (SEW2871, 5 mg/kg/day); sham surgery and daily ip injection for 7 days of SEW2871 after surgery; LtCCAO and daily ip injection for 7 days of SEW2871 and an S1PR1 inverse agonist (VPC23019, 0.5 mg/kg); LtCCAO and daily ip injection of DMSO for 7 days after surgery; and sham surgery and daily ip injection of DMSO for 7 days. Leptomeningeal anastomoses were visualized 14 days after LtCCAO by latex perfusion method, and a set of animals underwent subsequent permanent middle cerebral artery occlusion (pMCAO) 7days after the treatment termination. Neurological functions 1hour, 1, 4, and 7days and infarction volume 7days after pMCAO were evaluated. Results In parallel with the increase in S1PR1 mRNA levels, S1PR1 expression colocalized with endothelial cell markers in the leptomeningeal arteries, increased markedly on the side of the CCAO, and peaked 7 days after CCAO. Mitotic cell numbers in the leptomeningeal arteries increased after CCAO. Administration of the S1PR1 selective agonist significantly increased cerebral blood flow (CBF) and the diameter of leptomeningeal collateral vessels (42.9 ± 2.6 μm) compared with the controls (27.6 ± 5.7 μm; P < 0.01). S1PR1 inverse agonist administration diminished the effect of the S1PR1 agonist (P < 0.001). After pMCAO, S1PR1 agonist pretreated animals showed significantly smaller infarct volume (17.5% ± 4.0% vs. 7.7% ± 4.0%, P < 0.01) and better functional recovery than vehicle-treated controls. Conclusions These results suggest that S1PR1 is one of the principal regulators of leptomeningeal collateral recruitment at the site of increased shear stress and provide evidence that an S1PR1 selective agonist has a role in promoting collateral growth and preventing of ischemic damage and neurological dysfunction after subsequent stroke in patients with intracranial major artery stenosis or occlusion. PMID:26367258

Thalidomide Improves the Intestinal Mucosal Injury and Suppresses Mesenteric Angiogenesis and Vasodilatation by Down-Regulating Inflammasomes-Related Cascades in Cirrhotic Rats

PubMed Central

Li, Tzu-Hao; Huang, Chia-Chang; Yang, Ying-Ying; Lee, Kuei-Chuan; Hsieh, Shie-Liang; Hsieh, Yun-Cheng; Alan, Lin; Lin, Han-Chieh; Lee, Shou-Dong; Tsai, Chang-Youh

2016-01-01

Background and Aims By blocking TNFα-related effects, thalidomide not only inhibits hepatic fibrogenesis but improves peripheral vasodilatation and portal hypertension in cirrhotic rats. Nonetheless, the investigation of thalidomide's effects on splanchnic and collateral microcirculation has been limited. Our study explored the roles of intestinal and mesenteric TNFα along with inflammasome-related pathway in relation to cirrhosis and the splanchnic/collateral microcirculation. Methods Using in vivo and in vitro approaches, mechanisms of the effects of thalidomide on intestinal and mesenteric inflammatory, vasodilatory and angiogenic cascades-related abnormalities were explored in cirrhotic rats that had received 1-month thalidomide (C-T) treatment. Results In cirrhotic rats, high tumor necrosis factor (TNF)α, vascular endothelial growth factor (VEGF) and nitric oxide (NO)x levels were associated with the NOD-like receptors protein 3 (NLRP3), IL-1β and caspase-1 inflammasome over-expression in splenorenal shunt and mesenteric tissues. The thalidomide-related inhibition of mesenteric and splenorenal shunt inflammasome expression was accompanied by a significantly decreased intestinal mucosal injury and inflammasome immunohistochemical staining expression. Suppression of various angiogenic cascades, namely VEGF-NOS-NO, was paralleled by a decrease in mesenteric angiogenesis as detected by CD31 immunofluorescence staining and by reduced portosystemic shunting (PSS) in C-T rats. The down-regulation of the mesenteric and collateral vasodilatory VEGF-NOS-NO cascades resulted in a correction of vasoconstrictive hypo-responsiveness and in an attenuation of vasodilatory hyper-responsiveness when analyzed by in situ perfusion of the superior mesenteric arterial (SMA) and portosystemic collaterals. There was also a decrease in SMA blood flow and an increase in SMA resistance in the C-T rats. Additionally, acute incubation with thalidomide abolished TNFα-augmented VEGF-mediated migration of and tube formation of human umbilical vein endothelial cells, which was accompanied by corresponding changes in inflammatory and angiogenic substances release. Conclusions The suppression of inflammasome over-expression by chronic thalidomide treatment ameliorates inflammatory, angiogenic and vasodilatory cascades-related pathogenic changes in the splanchnic and collateral microcirculation of cirrhotic rats. Thalidomide seems to be a promising agent that might bring about beneficial changes to the disarrangements of peripheral, hepatic, splanchnic and collateral systems in cirrhosis. PMID:26820153

Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus.

PubMed

Buhl, E H; Han, Z S; Lörinczi, Z; Stezhka, V V; Karnup, S V; Somogyi, P

1994-04-01

1. The properties of a well-defined type of GABAergic local circuit neuron, the axo-axonic cell (n = 17), were investigated in rat hippocampal slice preparations. During intracellular recording we injected axo-axonic cells with biocytin and subsequently identified them with correlated light and electron microscopy. Employing an immunogold-silver intensification technique we showed that one of the physiologically characterized cells was immunoreactive for gamma-aminobutyric acid (GABA). 2. Axo-axonic cells were encountered in the dentate gyrus (n = 5) as well as subfields CA3 (n = 2) and CA1 (n = 10). They generally had smooth, beaded dendrites that extended throughout all hippocampal layers. Their axons ramified densely in the cell body layers and in the subjacent stratum oriens or hilus, respectively. Tested with electron microscopy, labeled terminals (n = 53) established synapses exclusively with the axon initial segment of principal cells in strata oriens and pyramidale and rarely in lower radiatum. Within a 400-microns slice a single CA1 axo-axonic cell was estimated to be in synaptic contact with 686 pyramidal cells. 3. Axo-axonic cells (n = 14) had a mean resting membrane potential of -65.1 mV, an average input resistance of 73.9 M omega, and a mean time constant of 7.7 ms. Action potentials were of short duration (389-microseconds width at half-amplitude) and had a mean amplitude of 64.1 mV. 4. Nine of 10 tested cells showed a varying degree of spike frequency adaptation in response to depolarizing current injection. Current-evoked action potentials were usually curtailed by a deep (10.2 mV) short-latency afterhyperpolarization (AHP) with a mean duration of 28.1 ms. 5. Cells with strong spike frequency accommodation (n = 5) had a characteristic firing pattern with numerous spike doublets. These appeared to be triggered by an underlying depolarizing afterpotential. In the same cells, prolonged bursts of action potentials were followed by a prominent long-duration AHP with a mean time constant of 1.15 s. 6. Axo-axonic cells responded to the stimulation of afferent pathways with short-latency excitatory postsynaptic potentials (EPSPs) or at higher stimulation intensity with up to three action potentials. Axo-axonic cells in the dentate gyrus could be activated by stimulating the CA3 area as well as the perforant path, whereas in the CA1 area responses were elicited after shocks to the perforant path, Schaffer collaterals, and the stratum oriens-alveus border. 7. In the CA1 area the EPSP amplitude increased in response to membrane hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

12 CFR 614.4245 - Collateral evaluation policies.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Collateral evaluation policies. 614.4245... OPERATIONS Collateral Evaluation Requirements § 614.4245 Collateral evaluation policies. (a) The board of... shall adopt well-defined and effective collateral evaluation policies and standards, that comply with...

Cerebral collaterals and collateral therapeutics for acute ischemic stroke.

PubMed

Winship, Ian R

2015-04-01

Cerebral collaterals are vascular redundancies in the cerebral circulation that can partially maintain blood flow to ischemic tissue when primary conduits are blocked. After occlusion of a cerebral artery, anastomoses connecting the distal segments of the MCA with distal branches of the ACA and PCA (known as leptomeningeal or pial collaterals) allow for partially maintained blood flow in the ischemic penumbra and delay or prevent cell death. However, collateral circulation varies dramatically between individuals, and collateral extent is significant predictor of stroke severity and recanalization rate. Collateral therapeutics attempt to harness these vascular redundancies by enhancing blood flow through pial collaterals to reduce ischemia and brain damage after cerebral arterial occlusion. While therapies to enhance collateral flow remain relatively nascent neuroprotective strategies, experimental therapies including inhaled NO, transient suprarenal aortic occlusion, and electrical stimulation of the parasympathetic sphenopalatine ganglion show promise as collateral therapeutics with the potential to improve treatment of acute ischemic stroke. © 2014 John Wiley & Sons Ltd.

Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.

PubMed

Ito, Wulf D; Lund, Natalie; Sager, Hendrik; Becker, Wiebke; Wenzel, Ulrich

2015-01-01

Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth. We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP‑1) on collateral proliferation and macrophage accumulation in these models Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP‑1 only enhanced vascular proliferation in diabetic animals. These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.

7 CFR 4287.113 - Release of collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Loans § 4287.113 Release of collateral. (a) All releases of collateral with a value exceeding $100,000... loan. The Agency may, at its discretion, require an appraisal of the remaining collateral in cases... (a) of this section, lenders may, over the life of the loan, release collateral (other than personal...

Spatio-Temporal Changes of Lymphatic Contractility and Drainage Patterns following Lymphadenectomy in Mice

PubMed Central

Kwon, Sunkuk; Agollah, Germaine D.; Wu, Grace; Sevick-Muraca, Eva M.

2014-01-01

Objective To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF) imaging, and to subsequently assess impact on metastasis. Background Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis. Methods Changes in lymphatic “pumping” function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis. Results NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN) removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy. Conclusions Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage. PMID:25170770

Status of systemic to pulmonary arterial collateral flow after the fontan procedure.

PubMed

Whitehead, Kevin K; Harris, Matthew A; Glatz, Andrew C; Gillespie, Matthew J; DiMaria, Michael V; Harrison, Neil E; Dori, Yoav; Keller, Marc S; Rome, Jonathan J; Fogel, Mark A

2015-06-15

The investigators recently validated a method of quantifying systemic-to-pulmonary arterial collateral flow using phase-contrast magnetic resonance imaging velocity mapping. Cross-sectional data suggest decreased collateral flow in patients with total cavopulmonary connections (TCPCs) compared with those with superior cavopulmonary connections (SCPCs). However, no studies have examined serial changes in collateral flow from SCPCs to TCPCs in the same patients. The aim of this study was to examine differences in collateral flow between patients with SCPCs and those with TCPCs. Collateral flow was quantified by 2 independent measures from 250 single-ventricle studies in 219 different patients (115 SCPC and 135 TCPC studies, 31 patients with both) and 18 controls, during routine studies using through-plane phase-contrast magnetic resonance imaging. Collateral flow was indexed to body surface area, aortic flow, and pulmonary venous flow. Regardless of indexing method, SCPC patients had significantly higher collateral flow than TCPC patients (1.64 ± 0.8 vs 1.03 ± 0.8 L/min/m(2), p <0.001). In 31 patients who underwent serial examinations, collateral flow as a fraction of aortic flow increased early after TCPC completion. In TCPC patients, indexed collateral flow demonstrated a significant negative correlation with time from TCPC. In conclusion, SCPC and TCPC patients demonstrate substantial collateral flow, with SCPC patients having higher collateral flow than TCPC patients overall. On the basis of the paired subset analysis, collateral flow does not decrease in the short term after TCPC completion and trends toward an increase. In the long term, however, collateral flow decreases over time after TCPC completion. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired Leptomeningeal Collateral Flow Contributes to the Poor Outcome following Experimental Stroke in the Type 2 Diabetic Mice

PubMed Central

Akamatsu, Yosuke; Nishijima, Yasuo; Lee, Chih Cheng; Yang, Shih Yen; Shi, Lei; An, Lin; Wang, Ruikang K.; Tominaga, Teiji

2015-01-01

Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects. PMID:25740515

13 CFR 120.1850 - Will the Collateral be held by SBA?

Code of Federal Regulations, 2010 CFR

2010-01-01

... Loan Program) § 120.1850 Will the Collateral be held by SBA? Yes, SBA or its expressly authorized agent... all Collateral for SISMBD Loans in a custodial account. Certificates held as Collateral must be in... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Will the Collateral be held by SBA...

Internal Carotid Artery Stenosis and Collateral Recruitment in Stroke Patients.

PubMed

Dankbaar, Jan W; Kerckhoffs, Kelly G P; Horsch, Alexander D; van der Schaaf, Irene C; Kappelle, L Jaap; Velthuis, Birgitta K

2017-04-24

Leptomeningeal collaterals improve outcome in stroke patients. There is great individual variability in their extent. Internal carotid artery (ICA) stenosis may lead to more extensive recruitment of leptomeningeal collaterals. The purpose of this study was to evaluate the association of pre-existing ICA stenosis with leptomeningeal collateral filling visualized with computed tomography perfusion (CTP). From a prospective acute ischemic stroke cohort, patients were included with an M1 middle cerebral artery (MCA) occlusion and absent ipsilateral, extracranial ICA occlusion. ICA stenosis was determined on admission CT angiography (CTA). Leptomeningeal collaterals were graded as good (>50%) or poor (≤50%) collateral filling in the affected MCA territory on CTP-derived vessel images of the admission scan. The association between ipsilateral ICA stenosis ≥70% and extent of collateral filling was analyzed using logistic regression. In a multivariable analysis the odds ratio (OR) of ICA stenosis ≥70% was adjusted for complete circle of Willis, gender and age. We included 188 patients in our analyses, 50 (26.6%) patients were classified as having poor collateral filling and 138 (73.4%) as good. Of the patients 4 with poor collateral filling had an ICA stenosis ≥70% and 14 with good collateral filling. Unadjusted and adjusted ORs of ICA stenosis ≥70% for good collateral filling were 1.30 (0.41-4.15) and 2.67 (0.81-8.77), respectively. Patients with poor collateral filling had a significantly worse outcome (90-day modified Rankin scale 3-6; 80% versus 52%, p = 0.001). No association was found between pre-existing ICA stenosis and extent of CTP derived collateral filling in patients with an M1 occlusion.

Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes.

PubMed

Rebello, L C; Bouslama, M; Haussen, D C; Grossberg, J A; Dehkharghani, S; Anderson, A; Belagaje, S R; Bianchi, N A; Grigoryan, M; Frankel, M R; Nogueira, R G

2017-06-01

Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were comparable between groups. Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On multivariable analysis, CASOD was an independent predictor of moderate/good collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke. © 2017 EAN.

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

PubMed

Ennaifer, Rym; B'chir Hamzaoui, Saloua; Larbi, Thara; Romdhane, Hayfa; Abdallah, Maya; Bel Hadj, Najet; M'rad, Sander

2015-03-01

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD. Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Cardiac veins: collateral venous drainage pathways in chronic hemodialysis patients.

PubMed

Ozmen, Evrim; Algin, Oktay

2016-07-12

Venous anomalies are diagnostic and therapeutic challenges. Subclavian or superior vena cava stenosis can be developed and venous return can be achieved via cardiac veins and coronary sinus in patients with central venous catheter for long-term hemodialysis. These types of abnormalities are not extremely rare especially in patients with a history of central venous catheter placement. Detection of these anomalies and subclavian vein stenosis before the surgical creation of hemodialysis fistulae or tunneled central venous catheter placement may prevent unnecessary interventions in those patients. Multidetector computed tomography (MDCT) technique can give further information when compared with fluoroscopy or digital subtraction angiography in the management of these patients. This case report describes interesting aspects of central vein complications in hemodialysis patients. As a conclusion, there are limited data about thoracic venous return, and further prospective studies with large patient number are required. MDCT with 3D reconstruction is particularly useful for the accurate evaluation of venous patency, variations, and collateral circulation. Also it is an excellent tool for choosing and planning treatment.

Balancing repair and tolerance of DNA damage caused by alkylating agents.

PubMed

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

PubMed Central

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2013-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

Collateral Circulation in Chronic Total Occlusions - an interventional perspective.

PubMed

Choo, Gim-Hooi

2015-09-09

Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Preoperative Evaluation of Collateral Venous Anastomoses in Meningioma Involving Cerebral Venous Sinus by Susceptibility Weighted Imaging

PubMed Central

Wang, Qing; He, Jingzhen; Ma, Xiangxing

2014-01-01

Abstract Precise preoperative identification of the collateral venous anastomoses is critical for proper surgical management of patients with meningioma involving sinus. This study was to assess the feasibility of susceptibility weighted imaging (SWI) to delineate the collateral venous anastomoses before surgery. Twenty-five patients with meningiomas that were involved in sinuses underwent surgery and the collateral anastomoses were evaluated with SWI and phase-contrast magnetic resonance venography (MRV) before surgery. The results obtained with SWI were compared with those obtained with MRV. Intraoperative findings were used as the gold standard. By surgery, a total of 98 collateral anastomotic veins were identified in the 25 patients. SWI depicted 85 collateral anastomotic veins close to the meningioma with a sensitivity of 87%, whereas MRV showed 57 collateral anastomotic veins with a sensitivity of 58%. The detectability of collateral anastomotic veins in SWI images was superior to MRV. The results suggest that SWI is superior to MRV and could provide more reliable information on the collateral venous anastomoses in patients with meningioma. PMID:25501068

Isolated Major Aortopulmonary Collateral as the Sole Pulmonary Blood Supply to an Entire Lung Segment.

PubMed

Kim, Hannah S; Grady, R Mark; Shahanavaz, Shabana

2017-01-01

Congenital systemic-to-pulmonary collateral arteries or major aortopulmonary collaterals are associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Though it is usually associated with congenital heart diseases, there is an increased incidence of isolated acquired aortopulmonary collaterals in premature infants with chronic lung disease. Interestingly, isolated congenital aortopulmonary collaterals can occur without any lung disease, which may cause congestive heart failure and require closure. We present a neonate with an echocardiogram that showed only left-sided heart dilation. Further workup with a CT angiogram demonstrated an anomalous systemic artery from the descending thoracic aorta supplying the left lower lobe. He eventually developed heart failure symptoms and was taken to the catheterization laboratory for closure of the collateral. However, with the collateral being the only source of blood flow to the entire left lower lobe, he required surgical unifocalization. Isolated aortopulmonary collaterals without any other congenital heart disease or lung disease are rare. Our patient is the first reported case to have an isolated aortopulmonary collateral being the sole pulmonary blood supply to an entire lung segment. Due to its rarity, there is still much to learn about the origin and development of these collaterals that possibly developed prenatally.

The Institutionalization of Service-Learning at the Independent Colleges and Universities of the Gulf Coast Region

ERIC Educational Resources Information Center

Lewing, Morgan; Shehane, Melissa

2017-01-01

Service-learning is a high-impact educational practice that benefits the community, the university, and students (Jacoby, 2015). It also represents an educational practice that specifically supports the integration of Christian thought and action within Christian institutions (Schaffer, 2004). The purpose of the study was to determine the level of…

Pleiotrophin levels are associated with improved coronary collateral circulation.

PubMed

Türker Duyuler, Pinar; Duyuler, Serkan; Gök, Murat; Kundi, Harun; Topçuoğlu, Canan; Güray, Ümit

2018-01-01

Elucidation of the underlying mechanisms of angiogenesis and arteriogenesis in coronary collateral formation is necessary for new therapies. Pleiotrophin is a secreted multifunctional cytokine and associated with the formation of functional cardiovascular neovascularization in a series of experimental animal models. We aimed to evaluate the serum levels of pleiotrophin in patients with chronic total coronary artery occlusion and poor or good collateral development. We included 88 consecutive patients (mean age of the entire population: 63.7±12.1 years, 68 male patients) with stable angina pectoris who underwent coronary angiography and had chronic total occlusion in at least one major coronary artery. Collateral grading was performed according to the Rentrop classification. After grading, patients were divided into poor collateral circulation (Rentrop grade 0 and 1) and good collateral circulation (Rentrop grades 2 and 3) groups. Serum pleiotrophin levels were measured using a commercial human ELISA kit. Fifty-eight patients had good and 30 patients had poor coronary collaterals. The good collateral group had higher serum pleiotrophin levels than the poor collateral group (690.1±187.9 vs. 415.3±165.9 ng/ml, P<0.001). Pleiotrophin levels were higher with higher Rentrop grade (P<0.001). In multivariate analysis, increased pleiotrophin was associated independently with good collateral development (odds ratio: 1.007; confidence interval: 1.003-1.012; P=0.002). This study showed that increased serum pleiotrophin levels are associated with better developed coronary collateral circulation. Further studies are needed to better understand the relationship.

Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

PubMed

Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

2017-06-01

Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

Tissue-engineered collateral ligament composite allografts for scapholunate ligament reconstruction: an experimental study.

PubMed

Endress, Ryan; Woon, Colin Y L; Farnebo, Simon J; Behn, Anthony; Bronstein, Joel; Pham, Hung; Yan, Xinrui; Gambhir, Sanjiv S; Chang, James

2012-08-01

In patients with chronic scapholunate (SL) dissociation or dynamic instability, ligament repair is often not possible, and surgical reconstruction is indicated. The ideal graft ligament would recreate both anatomical and biomechanical properties of the dorsal scapholunate ligament (dorsal SLIL). The finger proximal interphalangeal joint (PIP joint) collateral ligament could possibly be a substitute ligament. We harvested human PIP joint collateral ligaments and SL ligaments from 15 cadaveric limbs. We recorded ligament length, width, and thickness, and measured the biomechanical properties (ultimate load, stiffness, and displacement to failure) of native dorsal SLIL, untreated collateral ligaments, decellularized collateral ligaments, and SL repairs with bone-collateral ligament-bone composite collateral ligament grafts. As proof of concept, we then reseeded decellularized bone-collateral ligament-bone composite grafts with green fluorescent protein-labeled adipo-derived mesenchymal stem cells and evaluated them histologically. There was no difference in ultimate load, stiffness, and displacement to failure among native dorsal SLIL, untreated and decellularized collateral ligaments, and SL repairs with tissue-engineered collateral ligament grafts. With pair-matched untreated and decellularized scaffolds, there was no difference in ultimate load or stiffness. However, decellularized ligaments revealed lower displacement to failure compared with untreated ligaments. There was no difference in displacement between decellularized ligaments and native dorsal SLIL. We successfully decellularized grafts with recently described techniques, and they could be similarly reseeded. Proximal interphalangeal joint collateral ligament-based bone-collateral ligament-bone composite allografts had biomechanical properties similar to those of native dorsal SLIL. Decellularization did not adversely affect material properties. These tissue-engineered grafts may offer surgeons another option for reconstruction of chronic SL instability. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Associations Between Collateral Status and Thrombus Characteristics and Their Impact in Anterior Circulation Stroke.

PubMed

Alves, Heitor C; Treurniet, Kilian M; Dutra, Bruna G; Jansen, Ivo G H; Boers, Anna M M; Santos, Emilie M M; Berkhemer, Olvert A; Dippel, Diederik W J; van der Lugt, Aad; van Zwam, Wim H; van Oostenbrugge, Robert J; Lingsma, Hester F; Roos, Yvo B W E M; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

2018-02-01

Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome. Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome. A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003-0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals. Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clinical outcome was only present in patients with moderate and high collateral scores. URL: http://www.trialregister.nl. Unique identifier: NTR1804 and URL: http://www.controlled-trials.com Unique identifier: ISRCTN10888758. © 2018 The Authors.

25 CFR 502.5 - Collateral agreement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 2 2012-04-01 2012-04-01 false Collateral agreement. 502.5 Section 502.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.5 Collateral agreement. Collateral agreement means any contract, whether or not in writing...

25 CFR 502.5 - Collateral agreement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 2 2013-04-01 2013-04-01 false Collateral agreement. 502.5 Section 502.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.5 Collateral agreement. Collateral agreement means any contract, whether or not in writing...

25 CFR 502.5 - Collateral agreement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false Collateral agreement. 502.5 Section 502.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.5 Collateral agreement. Collateral agreement means any contract, whether or not in writing...

25 CFR 502.5 - Collateral agreement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Collateral agreement. 502.5 Section 502.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.5 Collateral agreement. Collateral agreement means any contract, whether or not in writing...

40 CFR 13.16 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS Collection § 13.16 Liquidation of collateral. Where the Administrator holds a security instrument with a power of sale or has physical possession of collateral, he may liquidate the security or... businesses, including liquidation of security or collateral, is not a prerequisite to requiring payment by a...

22 CFR 213.17 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Liquidation of collateral. Where the CFO holds a security instrument with a power of sale or has physical possession of collateral, he may liquidate the security or collateral and apply the proceeds to the overdue... circumstances require judicial foreclosure. However, collection from other businesses, including liquidation of...

Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium.

PubMed

Chen, Yingjie; Zhang, Ping; Li, Jingxin; Xu, Xin; Bache, Robert J

2014-02-01

Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with N(G)-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MVo2). The results suggest that NO produced by iNOS inhibits MVo2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MVo2. Thus the coordinated expression of iNOS to restrain MVo2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia.

Bleeding Duodenal Varices Successfully Treated with Balloon-Occluded Retrograde Transvenous Obliteration (B-RTO) Assisted by CT During Arterial Portography

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

Tsurusaki, Masakatsu, E-mail: he3m-trsk@asahi-net.or.jp; Sugimoto, Koji; Matsumoto, Shinichi

2006-12-15

A 60-year-old woman with massive hemorrhage from duodenal varices was transferred to our hospital for the purpose of transcatheter intervention. Although digital subtraction arterial portography could not depict the entire pathway of collateral circulation, the efferent route of the duodenal varices was clearly demonstrated on subsequent CT during arterial portography. Balloon-occluded retrograde transvenous obliteration (B-RTO) of the varices was performed via the efferent vein and achieved complete thrombosis of the varices.

Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics.

PubMed

Cragg, Mark S; Harris, Claire; Strasser, Andreas; Scott, Clare L

2009-05-01

Therapeutic targeting of tumours on the basis of molecular analysis is a new paradigm for cancer treatment but has yet to fulfil expectations. For many solid tumours, targeted therapeutics, such as inhibitors of oncogenic kinase pathways, elicit predominantly disease-stabilizing, cytostatic responses, rather than tumour regression. Combining oncogenic kinase inhibitors with direct activators of the apoptosis machinery, such as the BH3 mimetic ABT-737, may unlock potent anti-tumour potential to produce durable clinical responses with less collateral damage.

31 CFR 202.6 - Collateral security.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Collateral security. 202.6 Section 202... GOVERNMENT 1 § 202.6 Collateral security. (a) Requirement. Prior to receiving deposits of public money, a depositary authorized to perform services under § 202.3(b) must pledge collateral security in the amount...

31 CFR 202.6 - Collateral security.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Collateral security. 202.6 Section 202... GOVERNMENT 1 § 202.6 Collateral security. (a) Requirement. Prior to receiving deposits of public money, a depositary authorized to perform services under § 202.3(b) must pledge collateral security in the amount...

31 CFR 202.6 - Collateral security.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Collateral security. 202.6 Section 202... GOVERNMENT 1 § 202.6 Collateral security. (a) Requirement. Prior to receiving deposits of public money, a depositary authorized to perform services under § 202.3(b) must pledge collateral security in the amount...

45 CFR 1336.67 - Security and collateral: Responsibilities of the Loan Administrator.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) As a Credit Factor. The availability of collateral security normally is considered an important... 45 Public Welfare 4 2010-10-01 2010-10-01 false Security and collateral: Responsibilities of the... Fund Demonstration Project § 1336.67 Security and collateral: Responsibilities of the Loan...

Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

PubMed

Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

2015-05-01

Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

PubMed Central

Hill, Grace; Headon, Denis; Harris, Zoey I.; Huttner, Kenneth; Limesand, Kirsten H.

2014-01-01

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170

7 CFR 3575.90 - Disposition of acquired property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... collateral. Any collateral accepted by the lender must not be titled in the Agency's name in whole or in part... collateral must be maintained. (d) Collateral sale. (1) The lender will prepare and submit to the Agency a plan on the best method of sale, keeping in mind any prospective purchasers. The Agency must approve...

7 CFR 3575.90 - Disposition of acquired property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... collateral. Any collateral accepted by the lender must not be titled in the Agency's name in whole or in part... collateral must be maintained. (d) Collateral sale. (1) The lender will prepare and submit to the Agency a plan on the best method of sale, keeping in mind any prospective purchasers. The Agency must approve...

7 CFR 1779.90 - Disposition of acquired property.

Code of Federal Regulations, 2010 CFR

2010-01-01

... prepare and submit to the Agency a plan on the best method of sale, keeping in mind any prospective... develop a plan to fully protect the collateral, and the lender must dispose of the collateral without delay. (b) Re-title collateral. Any collateral accepted by the lender must not be titled in the Agency's...

Differences in the refractory properties of two distinct inhibitory circuitries in field CA1 of the hippocampus.

PubMed

Arai, A; Silberg, J; Lynch, G

1995-12-18

Extracellular reflections of IPSPs were examined in two distinct circuitries in field CA1 of the hippocampus. Stimulation in the stratum radiatum in the presence of AMPA receptor antagonists elicited positive potentials in the same stratum that were eliminated by picrotoxin, a blocker of GABAA receptors. Laminar profile analysis revealed that the response was maximal in the stratum radiatum at a point well distal to the pyramidal cell body layer and had a negative reflection in the stratum oriens. These field IPSPs presumably mediate the feedforward inhibition normally activated by the Schaffer-commissural projections to field CA1. Stimulation of the alveus produced an antidromic response followed by a much slower positive potential in recordings collected in the pyramidal cell layer. The latter response was suppressed by AMPA receptor antagonists or picrotoxin, as expected for disynaptic, recurrent (feedback) inhibition. The laminar profile for the feedback field IPSPs had its maximum near the pyramidal cell layer and its negative dipole in the stratum radiatum. Feedforward IPSPs were inhibited by about 50% if they were preceded within 200 ms by a priming pulse while feedback IPSPs were reduced by less than 20% under comparable conditions. The refractory effect was minimally dependent on stimulation intensity but was strongly affected by an antagonist of GABAB receptors. Attempts to modify IPSPs in the s. radiatum with long trains of low frequency stimulation or with theta-burst stimulation were not successful, suggesting that GABAergic synapses do not have the plasticities found in their glutamatergic counterparts. These results indicate that interneurons contacted by the extrinsic afferents of hippocampus form GABAergic synapses that differ in terms of spatial location and functional properties from the synapses generated by interneurons innervated by the recurrent collaterals of the pyramidal cells. The findings also suggest that repetitive afferent activity, while reducing the influence of dendritic IPSPs on excitatory input, will leave feedback suppression of cell spiking largely intact.

Developmental increase of asynchronic glutamate release from hippocampal synapses in mutant taiep rat.

PubMed

Fuenzalida, Marco; Aliaga, Esteban; Olivares, Virginia; Roncagliolo, Manuel; Bonansco, Christian

2009-06-01

During development, regulation of the strength of synaptic transmission plays a central role in the formation of mammalian brain circuitries. In taiep rat, a neurological mutant with severe reactive astrogliosis and demyelination, we have described alterations in the synaptic transmission in central neurons, characterized by asynchronous excitatory postsynaptic currents ((ASYN)EPSCs), because of delayed neurotransmitter release. This hippocampal synaptic dysfunction has been described in juvenile mutants, concomitantly with the appearance of their main glial alterations. However, it is unknown whether this abnormal synaptic activity is correlated with some alterations of synaptic maturation during the postnatal development. Using intracellular electrophysiological recordings and immunohistochemistry assays, we studied the maturation of CA3-CA1 synapses in taiep rats. In taiep, the number of (ASYN)EPSCs evoked by conventional stimulation of Schaffer collaterals increases with age (P7-P30) and can be evoked by stimulation of single fiber. The amplitude and frequency of spontaneous EPSC (sEPSC) increased during the postnatal development in both control and taiep rats. However, in taiep, the increase of sEPSC frequency was significantly higher than in the control rats. The frequency of miniature EPSC (mEPSC) increased over the studied age range, without differences between taiep and control rats. In both control and taiep groups, the synaptophysin immunostaining (SYP-IR) in the stratum radiatum of CA1 region was significantly lower in the juvenile (P30) than in the neonatal (P10) rats, suggesting that synaptic pruning is normally occurring in taiep, even when SYP-IR was higher in taiep than control in both ages studied. These results suggest that, in taiep mutants, the asynchronic transmission is due to a dysfunction in the glutamate release mechanisms that progressively increases during development, which is not attributable to the existence of aberrant synaptic contacts. Synapse 63:502-509, 2009. (c) 2009 Wiley-Liss, Inc.

Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term depression at CA3-CA1 synapses.

PubMed

Takayasu, Yukihiro; Takeuchi, Koichi; Kumari, Ranju; Bennett, Michael V L; Zukin, R Suzanne; Francesconi, Anna

2010-12-14

Group I metabotropic glutamate receptors (mGluR1/5) are important to synaptic circuitry formation during development and to forms of activity-dependent synaptic plasticity. Dysregulation of mGluR1/5 signaling is implicated in some disorders of neurodevelopment, including fragile X syndrome, the most common inherited form of intellectual disabilities and leading cause of autism. Site(s) in the intracellular loops of mGluR1/5 directly bind caveolin-1, an adaptor protein that associates with membrane rafts. Caveolin-1 is the main coat component of caveolae and organizes macromolecular signaling complexes with effector proteins and membrane receptors. We report that long-term depression (LTD) elicited by a single application of the group I mGluR selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was markedly attenuated at Schaffer collateral-CA1 synapses of mice lacking caveolin-1 (Cav1(-/-)), as assessed by field recording. In contrast, multiple applications of DHPG produced LTD comparable to that in WT mice. Passive membrane properties, basal glutamatergic transmission and NMDA receptor (NMDAR)-dependent LTD were unaltered. The remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms as in WT. mGluR1/5-dependent activation (phosphorylation) of MEK and extracellular signal-regulated kinase (ERK1/2) was altered in Cav1(-/-) mice; basal phosphorylation was increased, but a single application of DHPG had no further effect, and after DHPG, phosphorylation was similar in WT and Cav1(-/-) mice. Taken together, our findings suggest that caveolin-1 is required for normal coupling of mGluR1/5 to downstream signaling cascades and induction of mGluR-LTD.

VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy.

PubMed

Nickols, Hilary Highfield; Yuh, Joannes P; Gregory, Karen J; Morrison, Ryan D; Bates, Brittney S; Stauffer, Shaun R; Emmitte, Kyle A; Bubser, Michael; Peng, Weimin; Nedelcovych, Michael T; Thompson, Analisa; Lv, Xiaohui; Xiang, Zixiu; Daniels, J Scott; Niswender, Colleen M; Lindsley, Craig W; Jones, Carrie K; Conn, P Jeffrey

2016-01-01

Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have potential applications in the treatment of fragile X syndrome, levodopa-induced dyskinesia in Parkinson disease, Alzheimer disease, addiction, and anxiety; however, clinical and preclinical studies raise concerns that complete blockade of mGlu5 and inverse agonist activity of current mGlu5 NAMs contribute to adverse effects that limit the therapeutic use of these compounds. We report the discovery and characterization of a novel mGlu5 NAM, N,N-diethyl-5-((3-fluorophenyl)ethynyl)picolinamide (VU0477573) that binds to the same allosteric site as the prototypical mGlu5 NAM MPEP but displays weak negative cooperativity. Because of this weak cooperativity, VU0477573 acts as a "partial NAM" so that full occupancy of the MPEP site does not completely inhibit maximal effects of mGlu5 agonists on intracellular calcium mobilization, inositol phosphate (IP) accumulation, or inhibition of synaptic transmission at the hippocampal Schaffer collateral-CA1 synapse. Unlike previous mGlu5 NAMs, VU0477573 displays no inverse agonist activity assessed using measures of effects on basal [(3)H]inositol phosphate (IP) accumulation. VU0477573 acts as a full NAM when measuring effects on mGlu5-mediated extracellular signal-related kinases 1/2 phosphorylation, which may indicate functional bias. VU0477573 exhibits an excellent pharmacokinetic profile and good brain penetration in rodents and provides dose-dependent full mGlu5 occupancy in the central nervous system (CNS) with systemic administration. Interestingly, VU0477573 shows robust efficacy, comparable to the mGlu5 NAM MTEP, in models of anxiolytic activity at doses that provide full CNS occupancy of mGlu5 and demonstrate an excellent CNS occupancy-efficacy relationship. VU0477573 provides an exciting new tool to investigate the efficacy of partial NAMs in animal models. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy

PubMed Central

Yuh, Joannes P.; Gregory, Karen J.; Morrison, Ryan D.; Bates, Brittney S.; Stauffer, Shaun R.; Emmitte, Kyle A.; Bubser, Michael; Peng, Weimin; Nedelcovych, Michael T.; Thompson, Analisa; Lv, Xiaohui; Xiang, Zixiu; Daniels, J. Scott; Niswender, Colleen M.; Lindsley, Craig W.; Jones, Carrie K.; Conn, P. Jeffrey

2016-01-01

Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have potential applications in the treatment of fragile X syndrome, levodopa-induced dyskinesia in Parkinson disease, Alzheimer disease, addiction, and anxiety; however, clinical and preclinical studies raise concerns that complete blockade of mGlu5 and inverse agonist activity of current mGlu5 NAMs contribute to adverse effects that limit the therapeutic use of these compounds. We report the discovery and characterization of a novel mGlu5 NAM, N,N-diethyl-5-((3-fluorophenyl)ethynyl)picolinamide (VU0477573) that binds to the same allosteric site as the prototypical mGlu5 NAM MPEP but displays weak negative cooperativity. Because of this weak cooperativity, VU0477573 acts as a “partial NAM” so that full occupancy of the MPEP site does not completely inhibit maximal effects of mGlu5 agonists on intracellular calcium mobilization, inositol phosphate (IP) accumulation, or inhibition of synaptic transmission at the hippocampal Schaffer collateral-CA1 synapse. Unlike previous mGlu5 NAMs, VU0477573 displays no inverse agonist activity assessed using measures of effects on basal [3H]inositol phosphate (IP) accumulation. VU0477573 acts as a full NAM when measuring effects on mGlu5-mediated extracellular signal-related kinases 1/2 phosphorylation, which may indicate functional bias. VU0477573 exhibits an excellent pharmacokinetic profile and good brain penetration in rodents and provides dose-dependent full mGlu5 occupancy in the central nervous system (CNS) with systemic administration. Interestingly, VU0477573 shows robust efficacy, comparable to the mGlu5 NAM MTEP, in models of anxiolytic activity at doses that provide full CNS occupancy of mGlu5 and demonstrate an excellent CNS occupancy-efficacy relationship. VU0477573 provides an exciting new tool to investigate the efficacy of partial NAMs in animal models. PMID:26503377

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

PubMed Central

Speca, David J.; Ogata, Genki; Mandikian, Danielle; Bishop, Hannah I.; Wiler, Steve W.; Eum, Kenneth; Wenzel, H. Jürgen; Doisy, Emily T.; Matt, Lucas; Campi, Katharine L.; Golub, Mari S.; Nerbonne, Jeanne M.; Hell, Johannes W.; Trainor, Brian C.; Sack, Jon T.; Schwartzkroin, Philip A.; Trimmer, James S.

2014-01-01

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appears unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long-term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. PMID:24494598

Influence of oxidative stress on the development of collateral circulation in total coronary occlusions.

PubMed

Demirbag, Recep; Gur, Mustafa; Yilmaz, Remzi; Kunt, Alper Sami; Erel, Ozcan; Andac, M Halit

2007-03-02

The purpose of this study was to investigate whether the levels of total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) are associated with the development of collaterals in total coronary occlusions. Our study group contained 176 consecutive men patients with single-vessel TCO, 94 of whom had poorly developed coronary collateral, while 82 had well-developed coronary collateral. TAC and total peroxide concentration were measured of plasma. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress. The values of total peroxide and OSI in the Group I were significantly lower than that in Group II (p<0.001, for both). TAC levels were significantly higher in patients with poorly developed collaterals than in well-developed collateral group (p<0.001). OSI values were also significantly different among the Rentrop class-0, -1, -2 and -3 (ANOVA p<0.001). We found significant correlations between collaterals score and TAC, total peroxide and OSI levels (p<0.001 for all). In multiple linear regression analysis, total peroxide and OSI were independent predictors of collaterals score (p=0.006 and p<0.001 respectively). This study clearly demonstrates that the level of OSI is independently and positively associated with the presence of collateral circulation in total coronary occlusion patients.

Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger's disease): relationship between corkscrew type and prevalence of ischemic ulcers.

PubMed

Fujii, Yuichi; Soga, Junko; Nakamura, Shuji; Hidaka, Takayuki; Hata, Takaki; Idei, Naomi; Fujimura, Noritaka; Nishioka, Kenji; Chayama, Kazuaki; Kihara, Yasuki; Higashi, Yukihito

2010-08-01

A corkscrew collateral appearance on angiography is one of the diagnostic criteria for Buerger's disease. The purpose of the present study was to classify the angiographic findings of corkscrew collaterals and to evaluate the relationship between corkscrew collateral type and the severity of Buerger's disease. Corkscrew collaterals were assessed on digital subtraction angiography in lower extremities of 28 patients with Buerger's disease (55 limbs). The corkscrew sign was classified into 4 types by size and pattern as follows: type I, artery diameter >2 mm, large helical sign; type II, diameter >1.5 mm and or=1 mm and

Identification and two-photon imaging of oligodendrocyte in CA1 region of hippocampal slices

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

Zhou Wei; Ge Wooping; Zeng Shaoqun

2007-01-19

Oligodendrocyte (OL) plays a critical role in myelination and axon maintenance in central nervous system. Recent studies show that OL can also express NMDA receptors in development and pathological situations in white matter. There is still lack of studies about OL properties and function in gray matter of brain. Here we reported that some glial cells in CA1 region of rat hippocampal slices (P15-23) had distinct electrophysiological characteristics from the other glia cells in this region, while they displayed uniform properties with OL from white matter in previous report; therefore, they were considered as OL in hippocampus. By loading dyemore » in recording pipette and imaging with two-photon laser scanning microscopy, we acquired the high spatial resolution, three-dimension images of these special cells in live slices. The OL in hippocampus shows a complex process-bearing shape and the distribution of several processes is parallel to Schaffer fiber in CA1 region. When stimulating Schaffer fiber, OL displays a long duration depolarization mediated by inward rectifier potassium channel. This suggested that the OL in CA1 region could sense the neuronal activity and contribute to potassium clearance.« less

Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium

PubMed Central

Chen, Yingjie; Zhang, Ping; Li, Jingxin; Xu, Xin

2013-01-01

Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with NG-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MV̇o2). The results suggest that NO produced by iNOS inhibits MV̇o2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MV̇o2. Thus the coordinated expression of iNOS to restrain MV̇o2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia. PMID:24322607

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke.

PubMed

Boers, A M M; Sales Barros, R; Jansen, I G H; Berkhemer, O A; Beenen, L F M; Menon, B K; Dippel, D W J; van der Lugt, A; van Zwam, W H; Roos, Y B W E M; van Oostenbrugge, R J; Slump, C H; Majoie, C B L M; Marquering, H A

2018-06-01

Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship. From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined. A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score (ρ = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77-.86) and follow-up infarct volume (exponent β = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0-2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale ( P = .048) and on functional independence ( P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis. Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy. © 2018 by American Journal of Neuroradiology.

12 CFR 223.41 - What covered transactions are exempt from the quantitative limits and collateral requirements?

Code of Federal Regulations, 2010 CFR

2010-01-01

... quantitative limits and collateral requirements? 223.41 Section 223.41 Banks and Banking FEDERAL RESERVE SYSTEM... are exempt from the quantitative limits and collateral requirements? The following transactions are not subject to the quantitative limits of §§ 223.11 and 223.12 or the collateral requirements of § 223...

12 CFR 223.41 - What covered transactions are exempt from the quantitative limits and collateral requirements?

Code of Federal Regulations, 2013 CFR

2013-01-01

... quantitative limits and collateral requirements? 223.41 Section 223.41 Banks and Banking FEDERAL RESERVE SYSTEM... covered transactions are exempt from the quantitative limits and collateral requirements? The following transactions are not subject to the quantitative limits of §§ 223.11 and 223.12 or the collateral requirements...

12 CFR 223.41 - What covered transactions are exempt from the quantitative limits and collateral requirements?

Code of Federal Regulations, 2012 CFR

2012-01-01

... quantitative limits and collateral requirements? 223.41 Section 223.41 Banks and Banking FEDERAL RESERVE SYSTEM... are exempt from the quantitative limits and collateral requirements? The following transactions are not subject to the quantitative limits of §§ 223.11 and 223.12 or the collateral requirements of § 223...

12 CFR 223.41 - What covered transactions are exempt from the quantitative limits and collateral requirements?

Code of Federal Regulations, 2011 CFR

2011-01-01

... quantitative limits and collateral requirements? 223.41 Section 223.41 Banks and Banking FEDERAL RESERVE SYSTEM... are exempt from the quantitative limits and collateral requirements? The following transactions are not subject to the quantitative limits of §§ 223.11 and 223.12 or the collateral requirements of § 223...

12 CFR 223.41 - What covered transactions are exempt from the quantitative limits and collateral requirements?

Code of Federal Regulations, 2014 CFR

2014-01-01

... quantitative limits and collateral requirements? 223.41 Section 223.41 Banks and Banking FEDERAL RESERVE SYSTEM... covered transactions are exempt from the quantitative limits and collateral requirements? The following transactions are not subject to the quantitative limits of §§ 223.11 and 223.12 or the collateral requirements...

12 CFR 221.7 - Supplement: Maximum loan value of margin stock and other collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... value of margin stock and other collateral. (a) Maximum loan value of margin stock. The maximum loan... nonmargin stock and all other collateral. The maximum loan value of nonmargin stock and all other collateral... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Supplement: Maximum loan value of margin stock...

Management of concomitant large aortic aneurysm and severe stenosis of aortic arc.

PubMed

Ren, Shiyan; Sun, Guang; Yang, Yuguang; Liu, Peng

2014-01-01

Primary large saccular aortic aneurysm with high grade stenosis of aortic arc is rare, and no standard therapy is available. We have encountered one case and successfully treated using a hybrid interventional approach. A 59-year-old woman with a 7-day history of headache, dizziness and chest pain, and a 5-year history of hypertension admitted and was diagnosed with transverse aortic aneurysm with sever aortic stenosis, the huge saccular aneurysm was located behind the transverse aortic arc. During surgery, a bypass with graft from ascending aorta to left external iliac artery was made initially in order to ensure the blood supply to the left leg, afterward, a 40 mm × 160 mm covered stent was implanted to cover the orifice of aneurysm and was used as a supporting anchorage in the descending aorta, a second covered stent (20 mm × 100 mm) was implanted to expand the stenosis of aortic arc. Follow-up at 1.5-year after surgery, the patient has been doing well without any surgical complication. A collateral pathway between internal mammary artery and inferior epigastric artery via the superior epigastric artery was found on3-dimensional reconstruction before surgery. Interruption of the compensatory arterial collateral pathway in the patient with severe stenosis of aortic arc should be prevented if possible in order to ensure the satisfactory perfusion of the lower limbs of the body.In conclusion, a patient with transverse aortic aneurysm accompanied with severe aortic stenosis can be treated by hybrid surgery.

Pelvic Arterial Embolisation in a Trauma Patient with a Pre-Existing Aortobifemoral Graft

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

Abulaban, Osama; Hopkins, Jonathan; Willis, Andrew P.

2011-02-15

Pelvic fractures secondary to blunt trauma are associated with a significant mortality rate due to uncontrolled bleeding. Interventional radiology (IR) can play an important and central role in the management of such patients, offering definitive minimally invasive therapy and avoiding the need for high-risk surgery. Rapid access to whole-body computed tomography has been shown to improve survival in polytrauma patients and allows rapid diagnosis of vascular injury and assessment of suitability for endovascular therapy. IR can then target and treat the specific area of bleeding. Embolisation of bleeding pelvic arteries has been shown to be highly effective and should bemore » the treatment of choice in this situation. The branches of the internal iliac artery (IIA) are usually involved, and these arteries are accessed by way of IIA catheterisation after abdominal aortography. Occasionally these arteries cannot be accessed by way of this conventional route because of recent IIA ligation carried out surgically in an attempt to stop the bleeding or because (in the rare situation we describe here) these vessels are excluded secondary to previous aortoiliac repair. In this situation, knowledge of pelvic arterial collateral artery pathways is important because these will continue to supply pelvic structures whilst making access to deep pelvic branches challenging. We describe a rare case, which has not been previously reported in the literature, in which successful embolisation of a bleeding pelvic artery was carried out by way of the collateral artery pathways.« less

Biomarkers of coronary endothelial health: correlation with invasive measures of collateral function, flow and resistance in chronically occluded coronary arteries and the effect of recanalization.

PubMed

Ladwiniec, Andrew; Ettelaie, Camille; Cunnington, Michael S; Rossington, Jennifer; Thackray, Simon; Alamgir, Farquad; Hoye, Angela

2016-06-01

In the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. We measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6-8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. We did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6-8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). Recanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent.

Angiographic Structural Differentiation between Native Arteriogenesis and Therapeutic Synangiosis in Intracranial Arterial Steno-Occlusive Disease.

PubMed

Ooi, Y C; Laiwalla, A N; Liou, R; Gonzalez, N R

2016-06-01

Encephaloduroarteriosynangiosis has been shown to generate collateral vessels from the extracranial-to-intracranial circulation in patients with Moyamoya disease and intracranial arterial steno-occlusive disease. The mechanisms involved are not well-understood. We hypothesized that angiogenesis is the leading mechanism forming collaterals after encephaloduroarteriosynangiosis because there are no pre-existing connections. Angiogenesis-generated collaterals should exhibit higher architectural complexity compared with innate collaterals. Pre- and postoperative digital subtraction angiograms were analyzed in patients enrolled in a prospective trial of encephaloduroarteriosynangiosis surgery. Branching angioscore, tortuosity index, and local connected fractal dimension were compared between innate and postoperative collaterals. One hundred one angiograms (50 preoperative, 51 postoperative) were analyzed from 44 patients (22 with intracranial atherosclerosis and 22 with Moyamoya disease). There was a significantly higher median branching angioscore (13 versus 4, P < .001) and a lower median tortuosity index (1.08 versus 1.76, P < .001) in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals. Higher mean local fractal dimension peaks (1.28 ± 0.1 versus 1.16 ± 0.11, P < .001) were observed in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals for both intracranial atherosclerosis (P < .001) and Moyamoya disease (P < .001) groups. The observed increase in high connectivity was greater in the intracranial atherosclerosis group compared with patients with Moyamoya disease (P = .01). The higher median branching angioscore and local connected fractal dimension, along with the lower median tortuosity index of encephaloduroarteriosynangiosis collaterals, are consistent with the greater complexity observed in the process of sprouting and splitting associated with angiogenesis. © 2016 by American Journal of Neuroradiology.

13 CFR 123.513 - Does SBA require collateral on its Military Reservist EIDL?

Code of Federal Regulations, 2010 CFR

2010-01-01

..., or both. SBA will not decline a loan if you do not have a particular amount of collateral so long as SBA is reasonably sure that you can repay the loan. If you refuse to pledge the available collateral... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Does SBA require collateral on its...

13 CFR 120.1881 - How are payments on the Collateral allocated between the SISMBD borrower and repayment of the...

Code of Federal Regulations, 2010 CFR

2010-01-01

... are payments on the Collateral allocated between the SISMBD borrower and repayment of the SISMBD Loan? Unless otherwise provided in the Loan Agreements for a particular SISMBD Loan, any payment on Collateral... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How are payments on the Collateral...

13 CFR 120.1882 - What happens if funds to make required loan payments are not generated from the Collateral?

Code of Federal Regulations, 2010 CFR

2010-01-01

... required loan payments are not generated from the Collateral? 120.1882 Section 120.1882 Business Credit and... to make required loan payments are not generated from the Collateral? (a) The SISMBD is responsible... Collateral as set forth in the Loan Agreements, related documents and applicable law. (b) An SISMBD will have...

7 CFR 1434.16 - Release of the honey pledged as collateral for a loan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Release of the honey pledged as collateral for a loan... MARKETING ASSISTANCE LOAN AND LDP REGULATIONS FOR HONEY § 1434.16 Release of the honey pledged as collateral for a loan. (a)(1) A producer shall not move or dispose of any honey pledged as collateral for a loan...

7 CFR 1434.16 - Release of the honey pledged as collateral for a loan.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Release of the honey pledged as collateral for a loan... MARKETING ASSISTANCE LOAN AND LDP REGULATIONS FOR HONEY § 1434.16 Release of the honey pledged as collateral for a loan. (a)(1) A producer shall not move or dispose of any honey pledged as collateral for a loan...

Impact of coronary collaterals on in-hospital and 5-year mortality after ST-elevation myocardial infarction in the contemporary percutaneous coronary intervention era: a prospective observational study

PubMed Central

Hara, Masahiko; Sakata, Yasuhiko; Nakatani, Daisaku; Suna, Shinichiro; Nishino, Masami; Sato, Hiroshi; Kitamura, Tetsuhisa; Nanto, Shinsuke; Hori, Masatsugu; Komuro, Issei

2016-01-01

Objectives To evaluate the short-term and long-term prognostic impacts of acute phase coronary collaterals to occluded infarct-related arteries (IRA) after ST-elevation myocardial infarction (STEMI) in the percutaneous coronary intervention (PCI) era. Design A prospective observational study. Setting Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. Participants 3340 patients with STEMI from the OACIS database who were admitted to hospitals within 24 hours from the onset and who had a completely occluded IRA. Interventions Patients were divided into 4 groups according to the Rentrop collateral score (RCS) by angiography on admission (RCS-0, no visible collaterals; RCS-1, collaterals without IRA filling; RCS-2, collaterals with partial IRA filling; and RCS-3, collaterals with complete IRA filling). Primary outcome measures In-hospital and 5-year mortality. Results Patients with RCS-0/3 were older than patients with RCS-1/2, and the prevalence of previous myocardial infarction was highest in patients with RCS-3. Median peak creatinine phosphokinase levels decreased as RCS increases (p<0.001), suggesting the acute cardioprotective effects of collaterals. Although RCS-1 and RCS-2 collaterals were associated with better in-hospital mortality (adjusted OR 0.48, p=0.046 and 0.38, p=0.010 for RCS-1 and RCS-2, respectively) and 5-year mortality (adjusted HR 0.53, p=0.004 and 0.46, p<0.001 for RCS-1 and RCS-2, respectively) as compared with R-0, presence of RCS-3 collaterals was not associated with improved in-hospital (adjusted OR 1.35, p=0.331) and 5-year mortality (adjusted HR 0.98, p=0.920), possibly because worse clinical profiles in patients with RCS-3 may mask mortality benefit of coronary collaterals. Conclusions Presence of acute phase coronary collaterals such as RCS-1 and RCS-2 were associated with better in-hospital and 5-year mortality after STEMI in the contemporary PCI era. PMID:27412101

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

Morphological patterns of the collateral sulcus in the human brain.

PubMed

Huntgeburth, Sonja C; Petrides, Michael

2012-04-01

The collateral sulcal complex is an important landmark on the medial surface of the temporal lobe. Anteriorly, it delineates the limbic regions of the parahippocampal gyrus from the visual-processing areas of the fusiform gyrus. Posteriorly, it continues into the occipital lobe, bearing no relationship to the memory-related limbic regions. Given the considerable extent of the sulcus and functional heterogeneity of the surrounding cortex, an investigation of the morphology of this sulcus was carried out to examine whether it is continuous or a series of sulcal parts, i.e. independent sulci classified together under the name collateral sulcus. We investigated the collateral sulcal complex using magnetic resonance images taking into account the three-dimensional nature of the brain. Our examination demonstrated three separate sulcal segments: (i) an anterior segment, the rhinal sulcus, delineating the uncus from the adjacent temporal neocortex, (ii) a middle segment, the collateral sulcus proper, forming the lateral border of the posterior parahippocampal cortex, and (iii) a caudal segment, the occipital extent of the collateral sulcus, within the occipital lobe. Three relationships exist between the rhinal sulcus and collateral sulcus proper, only one being clearly identifiable from the surface. Posteriorly, the collateral sulcus proper and the occipital collateral sulcus, although appearing continuous on the brain surface, can be separated in the depth of the sulcus in all cases. These results provide quantification of the location and variability within standard stereotaxic space for the three collateral sulcus segments that could be used to aid accurate identification of functional activation peaks derived from neuroimaging studies. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease.

PubMed

Hartkamp, Nolan S; Petersen, Esben T; Chappell, Michael A; Okell, Thomas W; Uyttenboogaart, Maarten; Zeebregts, Clark J; Bokkers, Reinoud Ph

2017-01-01

Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres were compromised. Haemodynamic impairment in the affected brain region was always present in symptomatic patients. The degree of collateral blood flow was inversely correlated with haemodynamic impairment. Recruitment of secondary collaterals only occurred in symptomatic ICA occlusion patients. In conclusion, both CBF and cerebrovascular reactivity were found to be reduced in symptomatic patients with steno-occlusive ICA disease. The presence of collateral flow is associated with further haemodynamic impairment. Recruitment of secondary collaterals is associated with severe haemodynamic impairment.

Plastic modifications induced by object recognition memory processing

PubMed Central

Clarke, Julia Rosauro; Cammarota, Martín; Gruart, Agnès; Izquierdo, Iván; Delgado-García, José María

2010-01-01

Long-term potentiation (LTP) phenomenon is widely accepted as a cellular model of memory consolidation. Object recognition (OR) is a particularly useful way of studying declarative memory in rodents because it makes use of their innate preference for novel over familiar objects. In this study, mice had electrodes implanted in the hippocampal Schaffer collaterals–pyramidal CA1 pathway and were trained for OR. Field EPSPs evoked at the CA3-CA1 synapse were recorded at the moment of training and at different times thereafter. LTP-like synaptic enhancement was found 6 h posttraining. A testing session was conducted 24 h after training, in the presence of one familiar and one novel object. Hippocampal synaptic facilitation was observed during exploration of familiar and novel objects. A short depotentiation period was observed early after the test and was followed by a later phase of synaptic efficacy enhancement. Here, we show that OR memory consolidation is accompanied by transient potentiation in the hippocampal CA3-CA1 synapses, while reconsolidation of this memory requires a short-lasting phase of depotentiation that could account for its well described vulnerability. The late synaptic enhancement phase, on the other hand, would be a consequence of memory restabilization. PMID:20133798

Correcting deformity in total knee arthroplasty: Techniques to avoid the release of collateral ligaments in severely deformed knees.

PubMed

Mullaji, A B; Shetty, G M

2016-01-01

Collateral ligament release is advocated in total knee arthroplasty (TKA) to deal with significant coronal plane deformities, but is also associated with significant disadvantages. We describe steps to avoid release of the collateral (superficial medial and lateral collateral) ligaments during TKA in severely deformed knees, while correcting deformity and balancing the knee. ©2016 The British Editorial Society of Bone & Joint Surgery.

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models.

PubMed

Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C; Iruela-Arispe, M Luisa; Nih, Lina R; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

2013-04-01

Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-) mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

PubMed Central

Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S.; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C.; Iruela-Arispe, M. Luisa; Nih, Lina R.; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W.; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

2013-01-01

Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/- mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/- mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality. PMID:23533173

Activation of Cell Surface Bound 20S Proteasome Inhibits Vascular Cell Growth and Arteriogenesis

PubMed Central

Ito, Wulf D.; Lund, Natalie; Zhang, Ziyang; Buck, Friedrich; Lellek, Heinrich; Horst, Andrea; Machens, Hans-Günther; Schunkert, Heribert; Schaper, Wolfgang; Meinertz, Thomas

2015-01-01

Arteriogenesis is an inflammatory process associated with rapid cellular changes involving vascular resident endothelial progenitor cells (VR-EPCs). Extracellular cell surface bound 20S proteasome has been implicated to play an important role in inflammatory processes. In our search for antigens initially regulated during collateral growth mAb CTA 157-2 was generated against membrane fractions of growing collateral vessels. CTA 157-2 stained endothelium of growing collateral vessels and the cell surface of VR-EPCs. CTA 157-2 bound a protein complex (760 kDa) that was identified as 26 kDa α7 and 21 kDa β3 subunit of 20S proteasome in mass spectrometry. Furthermore we demonstrated specific staining of 20S proteasome after immunoprecipitation of VR-EPC membrane extract with CTA 157-2 sepharose beads. Functionally, CTA 157-2 enhanced concentration dependently AMC (7-amino-4-methylcoumarin) cleavage from LLVY (N-Succinyl-Leu-Leu-Val-Tyr) by recombinant 20S proteasome as well as proteasomal activity in VR-EPC extracts. Proliferation of VR-EPCs (BrdU incorporation) was reduced by CTA 157-2. Infusion of the antibody into the collateral circulation reduced number of collateral arteries, collateral proliferation, and collateral conductance in vivo. In conclusion our results indicate that extracellular cell surface bound 20S proteasome influences VR-EPC function in vitro and collateral growth in vivo. PMID:26146628

Rapid Liver Hypertrophy After Portal Vein Occlusion Correlates with the Degree of Collateralization Between Lobes-a Study in Pigs.

PubMed

Deal, Rebecca; Frederiks, Charles; Williams, Lauren; Olthof, Pim B; Dirscherl, Konstantin; Keutgen, Xavier; Chan, Edie; Deziel, Daniel; Hertl, Martin; Schadde, Erik

2018-02-01

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver growth than portal vein ligation (PVL). Transection of parenchyma in ALPPS may prevent the formation of collaterals between lobes. The aim of this study was to determine if abrogating the formation of collaterals through parenchymal transection impacted growth rate. Twelve Yorkshire Landrace pigs were randomized to undergo ALPPS, PVL, or "partial ALPPS" by varying degrees of parenchymal transection. Hepatic volume was measured after 7 days. Portal blood flow and pressure were measured. Portal vein collaterals were examined from epoxy casts. PVL, ALPPS, and partial ALPPS led to volume increases of the RLL by 15.5% (range 3-22), 64% (range 45-76), and 32% (range 18-77), respectively, with significant differences between PVL and ALPPS/partial ALPPS (p < 0.05). In PVL and partial ALPPS, substantial new portal vein collaterals were found. The number of collaterals correlated inversely with the growth rate (p = 0.039). Portal vein pressure was elevated in all models after ligation suggesting hyperflow to the portal vein-supplied lobe (p < 0.05). These data suggest that liver hypertrophy following PVL is inversely proportional to the development of collaterals. Hypertrophy after ALPPS is likely more rapid due to reduction of collaterals through transection.

30 CFR 800.21 - Collateral bonds.

Code of Federal Regulations, 2010 CFR

2010-07-01

... INSURANCE REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS BOND AND INSURANCE REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS UNDER REGULATORY PROGRAMS § 800.21 Collateral bonds... subject to the following conditions: (1) The regulatory authority shall keep custody of collateral...

Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium.

PubMed

Vukcevic, Vladan; Beleslin, Branko; Ostojic, Miodrag; Stojkovic, Sinisa; Stankovic, Goran; Nedeljkovic, Milan; Orlic, Dejan; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Giga, Vojislav; Arandjelovic, Aleksandra; Dikic, Miodrag; Kostic, Jelena; Nedeljkovic, Ivana; Nedeljkovic-Beleslin, Biljana; Saponjski, Jovica

2009-04-01

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium.

Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response

PubMed Central

Vandersmissen, Ine; Craps, Sander; Depypere, Maarten; Coppiello, Giulia; van Gastel, Nick; Maes, Frederik; Carmeliet, Geert; Schrooten, Jan; Jones, Elizabeth A.V.; Umans, Lieve; Devlieger, Roland; Koole, Michel; Gheysens, Olivier; Zwijsen, An; Aranguren, Xabier L.

2015-01-01

Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collateral arterial endothelium to transduce the extrinsic shear stimulus into an arteriogenic remodeling response. MSX1 was specifically up-regulated in remodeling collateral arteries. MSX1 induction in collateral endothelial cells (ECs) was shear stress driven and downstream of canonical bone morphogenetic protein–SMAD signaling. Flow recovery and collateral remodeling were significantly blunted in EC-specific Msx1/2 knockout mice. Mechanistically, MSX1 linked the arterial shear stimulus to arteriogenic remodeling by activating the endothelial but not medial layer to a proinflammatory state because EC but not smooth muscle cellMsx1/2 knockout mice had reduced leukocyte recruitment to remodeling collateral arteries. This reduced leukocyte infiltration in EC Msx1/2 knockout mice originated from decreased levels of intercellular adhesion molecule 1 (ICAM1)/vascular cell adhesion molecule 1 (VCAM1), whose expression was also in vitro driven by promoter binding of MSX1. PMID:26391659

Newer concepts in the pathophysiology of ischemic heart disease.

PubMed

Kirk, E S; Factor, S; Sonnenblick, E H

1984-11-01

Thus the thrust of these studies suggests that blood flow is the overwhelming factor in determining the consequences of the imbalance of oxygen supply and demand. Moreover, the factors that determine the requirements for tissue survival in the presence of deep ischemia are not the same as those shown for the normal myocardium in figure 1. In deep ischemia, contraction ceases, and metabolism shifts from aerobic to anaerobic pathways. Survival rather than contractile function then becomes the agenda. Not only does supply tend to overshadow demand in determining extent of transmural necrosis, but the anatomical pattern of supply precisely delineates the region at risk following a coronary occlusion as well as the ultimate extent of infarction. These views are summarized in the model presented in figures 12 and 13. The anatomic distribution of the ligated artery determines the lateral limits of the ischemic region (Fig. 12) and thus the lateral extension of necrosis (Fig. 13). The extension of the necrosis across the heart wall depends largely on the status of perfusion within the ischemic region. Extension of an infarct, should it occur, has to be explained by other mechanisms. These might include: (i) vascular obstruction in adjacent vascular systems that were not involved in the first occlusion, (ii) relative ischemia in the normal tissue surrounding the ischemic tissue due to an increased wall stress at the demarcation between contracting and noncontracting tissue, or (9) interruption of vessels supplying large interdigitations of normal tissue within the originally ischemic tissue due to changes associated with the process of infarction of ischemia. Alternatively, much that is called extension of infarction may involve more of the wall transmurally without lateral extension. Additional features of the development of myocardial infarction in figures 12 and 13 include: (i) the development of collateral vessel function resulting in an increased capacity to supply the ischemic area, and (ii) a redistribution of collateral blood flow from necrotic to surviving myocardium within the ischemic area. Thus, as coronary collaterals develop, collateral blood flow becomes increasingly heterogeneous within the ischemic area. Following a coronary occlusion, blood flow is reduced more in the subendocardium, and infarction occurs. Resistance to flow in infarcting tissue increase and causes a redistribution of flow to adjacent surviving layers of myocardium that life toward the epicardium. The process continues and combined with the enlargement of collateral vessels results in a sufficient flow to the epicardial layers so that they may survive.

45 CFR 160.532 - Collateral estoppel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Collateral estoppel. 160.532 Section 160.532 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS GENERAL ADMINISTRATIVE REQUIREMENTS Procedures for Hearings § 160.532 Collateral estoppel. When a...

41 CFR 105-55.014 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General Services Administration 55-COLLECTION OF CLAIMS OWED THE UNITED STATES § 105-55.014 Liquidation of collateral. (a) The General Services Administration (GSA) will liquidate security or collateral through the exercise of a...

12 CFR 725.19 - Collateral requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Collateral requirements. 725.19 Section 725.19 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.19 Collateral requirements. (a) Each...

Independent predictors of retrograde failure in CTO-PCI after successful collateral channel crossing.

PubMed

Suzuki, Yoriyasu; Muto, Makoto; Yamane, Masahisa; Muramatsu, Toshiya; Okamura, Atsunori; Igarashi, Yasumi; Fujita, Tsutomu; Nakamura, Shigeru; Oida, Akitsugu; Tsuchikane, Etsuo

2017-07-01

To evaluate factors for predicting retrograde CTO-PCI failure after successful collateral channel crossing. Successful guidewire/catheter collateral channel crossing is important for the retrograde approach in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). A total of 5984 CTO-PCI procedures performed in 45 centers in Japan from 2009 to 2012 were studied. The retrograde approach was used in 1656 CTO-PCIs (27.7%). We investigated these retrograde procedures to evaluate factors for predicting retrograde CTO-PCI failure even after successful collateral channel crossing. Successful guidewire/catheter collateral crossing was achieved in 77.1% (n = 1,276) of 1656 retrograde CTO-PCI procedures. Retrograde procedural success after successful collateral crossing was achieved in 89.4% (n = 1,141). Univariate analysis showed that the predictors for retrograde CTO-PCI failure were in-stent occlusion (OR = 1.9829, 95%CI = 1.1783 - 3.3370 P = 0.0088), calcified lesions (OR = 1.9233, 95%CI = 1.2463 - 2.9679, P = 0.0027), and lesion tortuosity (OR = 1.5244, 95%CI = 1.0618 - 2.1883, P = 0.0216). On multivariate analysis, lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing (OR = 1.3472, 95%CI = 1.0614 - 1.7169, P = 0.0141). The success rate of retrograde CTO-PCI following successful guidewire/catheter collateral channel crossing was high in this registry. Lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing. Devices and techniques to overcome complex CTO lesion morphology, such as lesion calcification, are required to further improve the retrograde CTO-PCI success rate. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

12 CFR 615.5050 - Collateral requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

....5050 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Collateral § 615.5050 Collateral requirements. (a) Each bank shall have on hand at the time of issuance of any notes, bonds, debentures, or other similar...

20 CFR 498.114 - Collateral estoppel.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Collateral estoppel. 498.114 Section 498.114 Employees' Benefits SOCIAL SECURITY ADMINISTRATION CIVIL MONETARY PENALTIES, ASSESSMENTS AND RECOMMENDED EXCLUSIONS § 498.114 Collateral estoppel. In a proceeding under section 1129 of the Social Security Act that...

42 CFR 402.15 - Collateral estoppel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Collateral estoppel. 402.15 Section 402.15 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CIVIL MONEY PENALTIES, ASSESSMENTS, AND EXCLUSIONS General Provisions § 402.15 Collateral estoppel...

28 CFR 94.25 - Collateral sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Collateral sources. 94.25 Section 94.25 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism... collateral source in connection with the same act of international terrorism. In cases in which a claimant...

28 CFR 94.25 - Collateral sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Collateral sources. 94.25 Section 94.25 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism... collateral source in connection with the same act of international terrorism. In cases in which a claimant...

28 CFR 94.25 - Collateral sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Collateral sources. 94.25 Section 94.25 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism... collateral source in connection with the same act of international terrorism. In cases in which a claimant...

28 CFR 94.25 - Collateral sources.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Collateral sources. 94.25 Section 94.25 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism... collateral source in connection with the same act of international terrorism. In cases in which a claimant...

28 CFR 94.25 - Collateral sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Collateral sources. 94.25 Section 94.25 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism... collateral source in connection with the same act of international terrorism. In cases in which a claimant...

7 CFR 762.142 - Servicing related to collateral.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 7 2014-01-01 2014-01-01 false Servicing related to collateral. 762.142 Section 762.142 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS GUARANTEED FARM LOANS § 762.142 Servicing related to collateral...

10 CFR 1015.210 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... States. Collection from other sources, including liquidation of security or collateral, is not a... Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COLLECTION OF CLAIMS OWED THE UNITED STATES Standards... liquidate security or collateral through the exercise of a power of sale in the security instrument or a...

13 CFR 120.343 - Collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Collateral. 120.343 Section 120.343 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Export Working Capital Program (ewcp) § 120.343 Collateral. A Borrower must give SBA a first security...

48 CFR 48.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Sharing collateral savings. 48.104-3 Section 48.104-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104-3 Sharing collateral savings. (a) The...

Diabetes Diminishes the Portal-Systemic Collateral Vascular Response to Vasopressin via Vasopressin Receptor and Gα Proteins Regulations in Cirrhotic Rats

PubMed Central

Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong

2013-01-01

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation. PMID:23874439

Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

PubMed

Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong

2013-01-01

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

42 CFR 1003.114 - Collateral estoppel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Collateral estoppel. 1003.114 Section 1003.114 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OIG AUTHORITIES CIVIL MONEY PENALTIES, ASSESSMENTS AND EXCLUSIONS § 1003.114 Collateral estoppel. (a) Where a...

42 CFR 3.532 - Collateral estoppel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Collateral estoppel. 3.532 Section 3.532 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.532 Collateral estoppel. When a final...

7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Warehouse-stored marketing assistance loan collateral... SIMILARLY HANDLED COMMODITIES-MARKETING ASSISTANCE LOANS AND LOAN DEFICIENCY PAYMENTS FOR 2008 THROUGH 2012 Marketing Assistance Loans § 1421.106 Warehouse-stored marketing assistance loan collateral. (a) A commodity...

7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Warehouse-stored marketing assistance loan collateral... SIMILARLY HANDLED COMMODITIES-MARKETING ASSISTANCE LOANS AND LOAN DEFICIENCY PAYMENTS FOR 2008 THROUGH 2012 Marketing Assistance Loans § 1421.106 Warehouse-stored marketing assistance loan collateral. (a) A commodity...

7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Warehouse-stored marketing assistance loan collateral... SIMILARLY HANDLED COMMODITIES-MARKETING ASSISTANCE LOANS AND LOAN DEFICIENCY PAYMENTS FOR 2008 THROUGH 2012 Marketing Assistance Loans § 1421.106 Warehouse-stored marketing assistance loan collateral. (a) A commodity...

10 CFR 609.15 - Default, demand, payment, and collateral liquidation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Default, demand, payment, and collateral liquidation. 609.15 Section 609.15 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS LOAN GUARANTEES FOR PROJECTS THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.15 Default, demand, payment, and collateral liquidation...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Sharing collateral savings. 2448.104-3 Section 2448.104-3 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Sharing collateral savings. 2448.104-3 Section 2448.104-3 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of...

Modulating Hippocampal Plasticity with In Vivo Brain Stimulation

DTIC Science & Technology

2015-09-16

persists in the Schaffer collateral–CA1 region of the hippocampus . NMDA-dependent LTP has been shown to be essential for learning and memory ...S114 –S121. CrossRef Medline Neves G, Cooke SF, Bliss TV (2008) Synaptic plasticity, memory and the hippocampus : a neural network approach to causality...and memory . Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects

12 CFR 615.5335 - Bank net collateral ratio.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Bank net collateral ratio. 615.5335 Section 615.5335 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Surplus and Collateral Requirements § 615.5335 Bank net...

13 CFR 120.349 - Collateral.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Collateral. 120.349 Section 120.349 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans International Trade Loans § 120.349 Collateral. Each IT loan must be secured either by a first lien position or...

10 CFR 609.16 - Perfection of liens and preservation of collateral.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Perfection of liens and preservation of collateral. 609.16 Section 609.16 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS LOAN GUARANTEES FOR PROJECTS THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.16 Perfection of liens and preservation of collateral. (a...

12 CFR 615.5090 - Reduction in carrying value of collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Reduction in carrying value of collateral. 615.5090 Section 615.5090 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Collateral § 615.5090 Reduction in...

12 CFR 615.5335 - Bank net collateral ratio.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Bank net collateral ratio. 615.5335 Section 615.5335 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FUNDING AND FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Surplus and Collateral Requirements § 615.5335 Bank net...

27 CFR 24.151 - Deposit of collateral security.

Code of Federal Regulations, 2013 CFR

2013-04-01

... pledged and deposited as collateral security in lieu of corporate sureties in accordance with the... furnished as collateral security in lieu of corporate sureties. (b) Treasury Department Circular No. 154 is... security. 24.151 Section 24.151 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE...

27 CFR 72.25 - Deposit of collateral.

Code of Federal Regulations, 2010 CFR

2010-04-01

... be pledged and deposited by claimants as collateral security in lieu of corporate sureties in... treasurers' checks may be furnished by claimants as collateral security in lieu of corporate sureties. (b..., Notes or Other Obligations Issued or Guaranteed by the United States as Security in Lieu of Surety or...

27 CFR 24.151 - Deposit of collateral security.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pledged and deposited as collateral security in lieu of corporate sureties in accordance with the... furnished as collateral security in lieu of corporate sureties. (b) Treasury Department Circular No. 154 is... security. 24.151 Section 24.151 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE...

27 CFR 72.25 - Deposit of collateral.

Code of Federal Regulations, 2012 CFR

2012-04-01

... be pledged and deposited by claimants as collateral security in lieu of corporate sureties in... treasurers' checks may be furnished by claimants as collateral security in lieu of corporate sureties. (b..., Notes or Other Obligations Issued or Guaranteed by the United States as Security in Lieu of Surety or...

27 CFR 24.151 - Deposit of collateral security.

Code of Federal Regulations, 2011 CFR

2011-04-01

... pledged and deposited as collateral security in lieu of corporate sureties in accordance with the... furnished as collateral security in lieu of corporate sureties. (b) Treasury Department Circular No. 154 is... security. 24.151 Section 24.151 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE...

27 CFR 72.25 - Deposit of collateral.

Code of Federal Regulations, 2013 CFR

2013-04-01

... be pledged and deposited by claimants as collateral security in lieu of corporate sureties in... treasurers' checks may be furnished by claimants as collateral security in lieu of corporate sureties. (b..., Notes or Other Obligations Issued or Guaranteed by the United States as Security in Lieu of Surety or...

27 CFR 72.25 - Deposit of collateral.

Code of Federal Regulations, 2014 CFR

2014-04-01

... be pledged and deposited by claimants as collateral security in lieu of corporate sureties in... treasurers' checks may be furnished by claimants as collateral security in lieu of corporate sureties. (b..., Notes or Other Obligations Issued or Guaranteed by the United States as Security in Lieu of Surety or...

27 CFR 24.151 - Deposit of collateral security.

Code of Federal Regulations, 2012 CFR

2012-04-01

... pledged and deposited as collateral security in lieu of corporate sureties in accordance with the... furnished as collateral security in lieu of corporate sureties. (b) Treasury Department Circular No. 154 is... security. 24.151 Section 24.151 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE...

27 CFR 72.25 - Deposit of collateral.

Code of Federal Regulations, 2011 CFR

2011-04-01

... be pledged and deposited by claimants as collateral security in lieu of corporate sureties in... treasurers' checks may be furnished by claimants as collateral security in lieu of corporate sureties. (b..., Notes or Other Obligations Issued or Guaranteed by the United States as Security in Lieu of Surety or...

27 CFR 24.151 - Deposit of collateral security.

Code of Federal Regulations, 2014 CFR

2014-04-01

... pledged and deposited as collateral security in lieu of corporate sureties in accordance with the... furnished as collateral security in lieu of corporate sureties. (b) Treasury Department Circular No. 154 is... security. 24.151 Section 24.151 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE...

13 CFR 120.395 - What is SBA's collateral position?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false What is SBA's collateral position? 120.395 Section 120.395 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Builders Loan Program § 120.395 What is SBA's collateral position? SBA will require...

13 CFR 120.395 - What is SBA's collateral position?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false What is SBA's collateral position? 120.395 Section 120.395 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Builders Loan Program § 120.395 What is SBA's collateral position? SBA will require...

13 CFR 120.395 - What is SBA's collateral position?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false What is SBA's collateral position? 120.395 Section 120.395 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Builders Loan Program § 120.395 What is SBA's collateral position? SBA will require...

13 CFR 120.395 - What is SBA's collateral position?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What is SBA's collateral position? 120.395 Section 120.395 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Builders Loan Program § 120.395 What is SBA's collateral position? SBA will require...

13 CFR 120.395 - What is SBA's collateral position?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false What is SBA's collateral position? 120.395 Section 120.395 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans Builders Loan Program § 120.395 What is SBA's collateral position? SBA will require...

Evaluation of the thickness of the medial ulnar collateral ligament in junior high and high school baseball players.

PubMed

Nagamoto, Hideaki; Yamamoto, Nobuyuki; Kurokawa, Daisuke; Takahashi, Hiroyuki; Muraki, Takayuki; Tanaka, Minoru; Koike, Yoichi; Sano, Hirotaka; Itoi, Eiji

2015-07-01

Thickening of the medial ulnar collateral ligament in the throwing arm of adult baseball players is a well-known phenomenon. However, onset of the thickening is unclear among young baseball players. The purpose of this study was to evaluate the thickness of the medial ulnar collateral ligament in junior high and high school baseball players. Seventy-one uninjured and asymptomatic junior high and high school baseball players were included in the study. Participants underwent physical examination after completing a questionnaire, followed by ultrasonographic evaluation. The thickness of the medial ulnar collateral ligament was measured bilaterally. The thickness of the throwing and non-throwing sides in high school and junior high school baseball players, and within each group, was compared and statistically analyzed. The medial ulnar collateral ligament in the throwing arm of high school baseball players was thicker than that in the non-throwing arm (5.5 vs. 4.4 mm), although no significant difference was seen in junior high school baseball players. High school baseball players showed a significantly thicker medial ulnar collateral ligament in the throwing arm than junior high school baseball players. Thickening of the medial ulnar collateral ligament in the throwing arm of asymptomatic and uninjured baseball players may begin by the time the players reach high school.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

PubMed

Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Injuries to the Collateral Ligaments of the Metacarpophalangeal Joint of the Thumb, Including Simultaneous Combined Thumb Ulnar and Radial Collateral Ligament Injuries, in National Football League Athletes.

PubMed

Werner, Brian C; Belkin, Nicole S; Kennelly, Steve; Weiss, Leigh; Barnes, Ronnie P; Rodeo, Scott A; Warren, Russell F; Hotchkiss, Robert N

2017-01-01

Thumb collateral ligament injuries occur frequently in the National Football League (NFL). In the general population or in recreational athletes, pure metacarpophalangeal (MCP) abduction or adduction mechanisms yield isolated ulnar collateral ligament (UCL) and radial collateral ligament (RCL) tears, respectively, while NFL athletes may sustain combined mechanism injury patterns. To evaluate the incidence of simultaneous combined thumb UCL and RCL tears among all thumb MCP collateral ligament injuries in NFL athletes on a single team. Case series; Level of evidence, 4. A retrospective review of all thumb injuries on a single NFL team from 1991 to 2014 was performed. All players with a thumb MCP collateral ligament injury were included. Collateral ligament injuries were confirmed by review of both physical examination findings and magnetic resonance imaging. Player demographics, surgical details, and return-to-play data were obtained from the team electronic medical record and surgeons' records. A total of 36 thumbs in 32 NFL players were included in the study, yielding an incidence of 1.6 thumb MCP collateral ligament injuries per year on a single NFL team. Of these, 9 thumbs (25%) had a simultaneous combined UCL and RCL tear injury pattern confirmed on both physical examination and MRI. The remaining 27 thumbs (75%) were isolated UCL injuries. All combined UCL/RCL injuries required surgery due to dysfunction from instability; 63.0% of isolated UCL injuries required surgical repair ( P = .032) due to continued pain and dysfunction from instability. Repair, when required, was delayed until the end of the season. All players with combined UCL/RCL injuries and isolated UCL injuries returned to play professional football the following season. Simultaneous combined thumb UCL and RCL tear is a previously undescribed injury pattern that occurred in 25% of thumb MCP collateral ligament injuries on a single NFL team over a 23-year period. All players with combined thumb UCL/RCL injuries required surgical repair, which was significantly higher compared with players with isolated UCL injuries. Team physicians and hand surgeons treating elite football players with suspected thumb collateral ligament injuries should examine for RCL and UCL instability and consider MRI if any concern exists for a combined ligament injury pattern, as this injury is likely frequently missed.

Embolization for Thoracic Duct Collateral Leakage in High-Output Chylothorax After Thoracic Surgery

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

Kariya, Shuji, E-mail: kariyas@hirakata.kmu.ac.jp; Nakatani, Miyuki, E-mail: nakatanm@hirakata.kmu.ac.jp; Yoshida, Rie, E-mail: yagir@hirakata.kmu.ac.jp

PurposeThis study was designed to investigate thoracic duct collateral leakage and the supply route of lymphatic fluid by lymphangiography and transcatheter thoracic ductography and to evaluate the results of embolization for thoracic duct collateral leakage performed to cut off this supply route.MethodsData were retrospectively collected from five patients who underwent embolization for thoracic duct collateral leakage in persistent high-output chylothorax after thoracic surgery. Extravasation of lipiodol at the ruptured thoracic duct collaterals was confirmed in all patients on lymphangiography. Transcatheter thoracic ductography was used to identify extravasation of iodinated contrast agent and to identify communication between the thoracic duct andmore » leakage site. Thoracic duct embolization (TDE) was performed using the percutaneous transabdominal approach to cut off the supply route using N-butyl cyanoacrylate (NBCA) mixed with lipiodol (1:5–1:20).ResultsClinical success (drainage volume ≤10 mL/kg/day within 7 days after TDE) was achieved in all patients. The collateral routes developed as consequence of surgical thoracic duct ligation. In three patients, NBCA-Lipiodol reached the leakage site through direct communication between the thoracic duct and the ruptured lymphatic duct. In the other two patients, direct communication and extravasation was not detected on thoracic ductography, and NBCA-Lipiodol did not reach the leakage site. However, NBCA-Lipiodol did reach the cisterna chyli, lumbar trunks, and some collateral routes via the cisterna chyli or lumbar lymphatics. As a result, leakage was stopped.ConclusionsTDE was effective for the management of leakage of the collaterals in high-output chylothorax after thoracic surgery.« less

Reciprocal ST-Segment Changes in Myocardial Infarction: Ischemia at Distance Versus Mirror Reflection of ST-Elevation.

PubMed

Vaidya, Gaurang Nandkishor; Antoine, Steve; Imam, Syed Haider; Kozman, Hani; Smulyan, Harold; Villarreal, Daniel

2018-02-01

Reciprocal ST-depression in the electrocardiograms (ECGs) of patients with ST-elevation myocardial infarction (STEMI) results from either true ischemia at a distance via collateral circulation diverting blood to the infarcted region or an electrical phenomenon that results from a mirror reflection of ST-elevation. We aimed to identify the role of reciprocal ECG changes in predicting collateral circulation to the infarcted area determined angiographically. In a retrospective study, ECG and angiography of 53 STEMI patients admitted to SUNY Upstate Medical University in 2014 were reviewed independently by experts blinded to the results of ECG and coronary angiography. Reciprocal changes (RC) in ECG were present in 41 patients (77%) and on angiography, 14 patients (26%) exhibited collateral vessels to the ischemic areas. No correlation was found between the presence of RC and collateral circulation (P = 0.384), or between the depth of reciprocal ST-depression and the degree of the collateral circulation (P = 0.195). However, 84% of patients without collaterals exhibited resolution of RC after successful percutaneous coronary intervention (PCI) (P = 0.036), suggesting that the ST depressions that resolved after reperfusion were directly caused by the culprit vessel. Patients without RC presented late after symptom onset (9.25 versus 3.83 hours, P = 0.004), also suggesting time related resolution. RC had no relation to or predictive value for collaterals on angiography. Among late presenting patients, RC were less frequent. Thus, reciprocal ST-depression may represent subendocardial ischemia from the primary coronary event or simply an electrical phenomenon, rather than ischemia at distance from impaired collateral circulation. Published by Elsevier Inc.

Pattern of venous collateral development after splenic vein occlusion in an extended Whipple procedure : comparison with collateral vein pattern in cases of sinistral portal hypertension.

PubMed

Strasberg, Steven M; Bhalla, Sanjeev; Sanchez, Luis A; Linehan, David C

2011-11-01

The risks of developing sinistral portal hypertension as a result of occlusion of the splenic vein close to its termination during a Whipple procedure are unclear. Our purpose was to compare the pattern of venous collateral development after splenic vein ligation in an extended Whipple procedure with the pattern of collateral development in cases of sinistral portal hypertension. Five patients underwent an extended Whipple procedure in which the splenic vein was divided and not reconstructed. Six to eight months later detailed mapping of venous return from the spleen was determined by contrast-enhanced multidetector computed tomography or in one case by 3D contrast-enhanced MRI. Spleen size and length of residual patent splenic vein were also measured. The literature on sinistral portal hypertension was evaluated to ascertain whether the venous collateral pattern in cases of left-sided portal hypertension was similar to the pattern that developed when the splenic vein was ligated at its termination in the Whipple procedure. A length of splenic vein remained patent in all five patients, measuring 4.5 to 11.5 cm from the spleen. Splenomegaly did not develop. Blood returned from the spleen by multiple collaterals including collaterals in the omentum and mesocolon. These types of collaterals do not develop in sinistral portal hypertension, nor is residual patent splenic vein seen. Ligation of the splenic vein close to its termination in five patients resulted in a pattern of venous return different from patients that have developed left-sided portal hypertension.

Collateral status and tissue outcome after intra-arterial therapy for patients with acute ischemic stroke.

PubMed

Boers, Anna Mm; Jansen, Ivo Gh; Berkhemer, Olvert A; Yoo, Albert J; Lingsma, Hester F; Slump, Cornelis H; Roos, Yvo Bwem; van Oostenbrugge, Robert J; Dippel, Diederik Wj; van der Lugt, Aad; van Zwam, Wim H; Marquering, Henk A; Majoie, Charles Blm

2017-11-01

Intra-arterial therapy (IAT) for ischemic stroke aims to save brain tissue. Collaterals are thought to contribute to prolonged penumbra sustenance. In this study, we investigate the effect of collateral status on brain tissue salvage with IAT. In 500 patients randomized between IAT and standard care, collateral status was graded from 0 (absent) to 3 (good). Final infarct volumes (FIV) were calculated on post-treatment CT. FIVs were compared between treatment groups per collateral grade. Multivariable linear regression with interaction terms was performed to study whether collaterals modified IAT effect on FIV. Four-hundred-forty-nine patients were included in the analysis. Median FIV for the IAT group was significantly lower with 54.5 mL (95% IQR: 21.8-145.0) than for the controls with 81.8 mL (95% IQR: 40.0-154.0) ( p = 0.020). Treatment effect differed across collateral grades, although there was no significant interaction (unadjusted p = 0.054; adjusted p = 0.105). For grade 3, IAT resulted in a FIV reduction of 30.1 mL ( p = 0.024). For grade 2 and 1, this difference was, respectively, 28.4 mL ( p = 0.028) and 28.4 mL ( p = 0.29). For grade 0, this was 88.6 mL ( p = 0.28) in favour of controls. IAT saves substantially more brain tissue as compared to standard care. We observed a trend of increasing effect of IAT with higher collateral grades.

12 CFR 223.42 - What covered transactions are exempt from the quantitative limits, collateral requirements, and...

Code of Federal Regulations, 2012 CFR

2012-01-01

... quantitative limits, collateral requirements, and low-quality asset prohibition? 223.42 Section 223.42 Banks... 23A § 223.42 What covered transactions are exempt from the quantitative limits, collateral requirements, and low-quality asset prohibition? The following transactions are not subject to the quantitative...

12 CFR 223.42 - What covered transactions are exempt from the quantitative limits, collateral requirements, and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... quantitative limits, collateral requirements, and low-quality asset prohibition? 223.42 Section 223.42 Banks... 23A § 223.42 What covered transactions are exempt from the quantitative limits, collateral requirements, and low-quality asset prohibition? The following transactions are not subject to the quantitative...

12 CFR 223.42 - What covered transactions are exempt from the quantitative limits, collateral requirements, and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... quantitative limits, collateral requirements, and low-quality asset prohibition? 223.42 Section 223.42 Banks... 23A § 223.42 What covered transactions are exempt from the quantitative limits, collateral requirements, and low-quality asset prohibition? The following transactions are not subject to the quantitative...

12 CFR 7.1009 - National bank holding collateral stock as nominee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false National bank holding collateral stock as nominee. 7.1009 Section 7.1009 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Bank Powers § 7.1009 National bank holding collateral stock as nominee...

12 CFR 7.1009 - National bank holding collateral stock as nominee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 1 2011-01-01 2011-01-01 false National bank holding collateral stock as nominee. 7.1009 Section 7.1009 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Bank Powers § 7.1009 National bank holding collateral stock as nominee...

Using OCT-based microangiography for in vivo longitudinal study of arteriogenesis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Yuandong; Choi, Woo June; Wang, Ruikang K.

2017-03-01

The adaptive growth of collateral vessels, termed "arteriogenesis", is crucial for maintaining regional blood supply during arterial obstruction and offsetting the adverse effect of tissue ischemia. Stimulation of arteriogenesis has been applied for the treatment of occlusive vascular diseases, and in vivo imaging of the progressive development of collateral vessel will facilitate a better understanding of the mechanism. We present using high-resolution OCT-based microangiography (OMAG) to image arteriogenesis process longitudinally in mouse cerebral cortex after middle cerebral artery occlusion (MCAO). We imaged the collateral arterioles at the arteriolo-arteriolar anastomosis (AAA) within 7-day period after MCAO to reveal key elements of collateral vessel remodeling, including alteration in vessel morphology, velocity and directionality of blood flow. The magnitudes of changes in these parameters matched the time course of the active building of collateral vessels stated in previous studies using histology. Hence, OMAG is a promising imaging tool for non-invasive longitudinal study of functional collateral vessel growth in small animal models and can be potentially applied in the experimental study of arteriogenesis stimulation.

Assessment of intracranial collaterals on CT angiography in anterior circulation acute ischemic stroke.

PubMed

Yeo, L L L; Paliwal, P; Teoh, H L; Seet, R C; Chan, B P; Ting, E; Venketasubramanian, N; Leow, W K; Wakerley, B; Kusama, Y; Rathakrishnan, R; Sharma, V K

2015-02-01

Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010-2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0-1 and 5-6 points, respectively. Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079-1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560-20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203-5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113-6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075-6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156-6.237; P = .022) were independent predictors of extremely poor outcomes. Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals. © 2015 by American Journal of Neuroradiology.

Revision ulnar collateral ligament reconstruction using a suspension button fixation technique.

PubMed

Lee, Gregory H; Limpisvasti, Orr; Park, Maxwell C; McGarry, Michelle H; Yocum, Lewis A; Lee, Thay Q

2010-03-01

Revision ulnar collateral ligament reconstruction remains a challenging problem. The objective of this study was to biomechanically evaluate an ulnar collateral ligament reconstruction technique using a suspension button fixation technique that can be used even in the case of ulnar cortical bone loss. An ulnar suspension fixation technique for ulnar collateral ligament reconstruction can restore elbow kinematics and demonstrate failure strength comparable to that of currently available techniques. Controlled laboratory study. Nine pairs of cadaveric elbows were dissected free of soft tissue and potted. After simulating ulnar cortical bone loss, ulnar collateral ligament reconstruction was performed in 1 elbow of each pair using palmaris longus autograft and a 30-mm RetroButton suspended from the far (lateralmost) ulnar cortex. A docking technique was used for humeral fixation of the graft. Elbow valgus angle was quantified using a Microscribe 3DLX digitizer at multiple elbow flexion angles. Valgus angle was measured with the ulnar collateral ligament intact, transected, and reconstructed. In addition, load-to-failure testing was performed in 1 elbow of each pair. Release of the ulnar collateral ligament caused a significant increase in valgus angle at each flexion angle tested (P < .002). Reconstructed elbows demonstrated no significant differences in valgus angle from the intact elbow at all flexion angles tested. Load-to-failure tests showed that reconstructed elbows had an ultimate torque (10.3 + or - 5.7 N x m) significantly less than intact elbows (26.4 + or - 10.6 N x m) (P = .001). Ulnar collateral ligament reconstruction using a suspension button fixation technique reliably restored elbow kinematics to the intact state. Load-to-failure testing demonstrated comparable fixation strength to several historic controls of primary reconstruction techniques despite the simulated ulnar cortical bone loss. Ulnar collateral ligament reconstruction using a suspension button fixation technique can be considered in the case of ulnar cortical bone loss in a primary or revision setting.

Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis.

PubMed

Leng, Xinyi; Fang, Hui; Leung, Thomas W H; Mao, Chen; Miao, Zhongrong; Liu, Liping; Wong, Ka Sing; Liebeskind, David S

2016-05-01

We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions. Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted. In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods. Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The receptor for advanced glycation end products impairs collateral formation in both diabetic and non-diabetic mice.

PubMed

Hansen, Laura M; Gupta, Divya; Joseph, Giji; Weiss, Daiana; Taylor, W Robert

2017-01-01

Diabetics often have poor perfusion in their limbs as a result of peripheral artery disease and an impaired ability to generate collateral vessels. The receptor for advanced glycation end products (RAGE) is one protein that is thought to play a detrimental role in collateral development in diabetics due to increased levels of advanced glycation end products (AGE), one of its ligands, in diabetes. Thus, the aim of this study was to investigate the role of RAGE in both diabetic and non-diabetic settings in a model of collateral formation in mice. Streptozotocin was used to induce diabetes in both wild type and RAGE knockout mice. Increased levels of the AGE, N ɛ -(carboxymethyl) lysine (CML), were confirmed via an ELISA. A hindlimb ischemia model, in which the femoral artery is ligated, was used to drive collateral growth and reperfusion was assessed using laser Doppler perfusion imaging and histological analysis of vessels in the muscle. Both of these measurements showed impaired collateral growth in diabetic compared with wild-type mice as well as improved collateral growth in both diabetic and non-diabetic RAGE knockout mice when compared their wild-type counterparts. Distance on a freely accessed running wheel, used as a measure of perfusion recovery, showed that wild-type diabetic mice had functionally impaired recovery compared with their wild-type counterparts. Immunohistochemistry and immunoblotting showed that HMGB-1 (high-mobility group box 1), another RAGE ligand, was increased in the ischemic leg compared with the non-ischemic leg in all mice. This increase in HMGB-1 may explain improvement in animals lacking RAGE and its subsequent signaling. In conclusion, this study shows that RAGE impairs collateral growth in a diabetic setting and also in a non-diabetic setting. This demonstrates the importance of RAGE and alternate RAGE ligands in the setting of collateral vessel growth.

Transluminal Angioplasty of Peroneal Artery Branches in Diabetics: Initial Technical Experience

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

Graziani, Lanfroi, E-mail: langrazi@tin.it; Silvestro, Antonio; Monge, Luca

2008-01-15

The present study aimed to report the technical feasibility of percutaneous transluminal angioplasty (PTA) of obstructed or insufficient collateral branches (anterior and posterior perforating branches) from distal peroneal to foot arteries in diabetic patients with chronic critical limb ischemia (CLI) and chronic noncrossable occlusion of the anterior and posterior tibial arteries. Twenty-four diabetic CLI patients (age, 67 {+-} 8 years; 87% males) undergoing collateral PTA were included. Baseline clinical angiographic and follow-up data were retrospectively reviewed. Collateral PTA was associated with a concomitant PTA of other sites in 21 (83%) cases. In 15 cases the treated collateral linked the peronealmore » with the plantaris communis; in 9 cases, the peroneal with the dorsalis pedis. Angiographic results of collateral PTA were good in 13 cases (<30% residual stenosis), whereas the result was considered moderate (30%-49% residual stenosis) in the remaining cases. Neither perforation nor acute occlusion of the treated collaterals or other relevant complications were observed. Mean follow-up was 32 {+-} 17 months. Major amputation was necessary for two (8.3%) patients. Cumulative limb salvage rates at 2 and 4 years were 96% and 87%, respectively. In conclusion, this initial experience shows that PTA of the collateral branches from distal peroneal to foot arteries is a feasible technique. Future studies are required to define the clinical role of this novel approach.« less

Pakistan’s Inter-Services Intelligence Directorate: A State within a State?

DTIC Science & Technology

2008-01-01

Robinson, Bin Laden: Behind the Mask of the Terrorist (New York: Arcade Publishing, 2001), 95. 26 Abbas, 114. 27 Mary Ann Weaver, Pakistan: In the...The Truth Behind the Most Devastating Terror- ist Attack the World Has Ever Seen (New York: Arcade Publishing, 2003), 50. 77 Teresita C. Schaffer...2004), 37. 78 Robert Fisk, The Great War for Civilisation : The Conquest of the Middle East (New York: Knopf, 2005), 862. 79 Peter R. Lavoy

17 CFR 210.3-16 - Financial statements of affiliates whose securities collateralize an issue registered or being...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Financial statements of affiliates whose securities collateralize an issue registered or being registered. 210.3-16 Section 210.3-16... constitute a substantial portion of collateral if the aggregate principal amount, par value, or book value of...

13 CFR 120.545 - What are SBA's policies concerning the liquidation of collateral and the sale of business loans...

Code of Federal Regulations, 2010 CFR

2010-01-01

... the liquidation of collateral and the sale of business loans and physical disaster assistance loans, physical disaster business loans and economic injury disaster loans? 120.545 Section 120.545 Business... policies concerning the liquidation of collateral and the sale of business loans and physical disaster...

13 CFR 123.11 - Does SBA require collateral for any of its disaster loans?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Does SBA require collateral for any of its disaster loans? 123.11 Section 123.11 Business Credit and Assistance SMALL BUSINESS...? Generally, SBA will not require that you pledge collateral to secure a disaster home loan or a physical...

Better Management of Collateral Can Reduce Losses in SBA’s Major Loan Program.

DTIC Science & Technology

1981-07-17

Inadequate or omitted appraisals may lead to failure to obtain fair value for the collateral liquidated and a lack of assurance of maximum recovery. For...lacked assurance that it was re- ceiving fair value for its collateral and may have failed to maximize recovery by as much as $1,500. More thorough and

Computer-assisted measurements of coronal knee joint laxity in vitro are related to low-stress behavior rather than structural properties of the collateral ligaments.

PubMed

Wilson, W T; Deakin, A H; Wearing, S C; Payne, A P; Clarke, J V; Picard, F

2013-01-01

The relationship between coronal knee laxity and the restraining properties of the collateral ligaments remains unknown. This study investigated correlations between the structural properties of the collateral ligaments and stress angles used in computer-assisted total knee arthroplasty (TKA), measured with an optically based navigation system. Ten fresh-frozen cadaveric knees (mean age: 81 ± 11 years) were dissected to leave the menisci, cruciate ligaments, posterior joint capsule and collateral ligaments. The resected femur and tibia were rigidly secured within a test system which permitted kinematic registration of the knee using a commercially available image-free navigation system. Frontal plane knee alignment and varus-valgus stress angles were acquired. The force applied during varus-valgus testing was quantified. Medial and lateral bone-collateral ligament-bone specimens were then prepared, mounted within a uni-axial materials testing machine, and extended to failure. Force and displacement data were used to calculate the principal structural properties of the ligaments. The mean varus laxity was 4 ± 1° and the mean valgus laxity was 4 ± 2°. The corresponding mean manual force applied was 10 ± 3 N and 11 ± 4 N, respectively. While measures of knee laxity were independent of the ultimate tensile strength and stiffness of the collateral ligaments, there was a significant correlation between the force applied during stress testing and the instantaneous stiffness of the medial (r = 0.91, p = 0.001) and lateral (r = 0.68, p = 0.04) collateral ligaments. These findings suggest that clinicians may perceive a rate of change of ligament stiffness as the end-point during assessment of collateral knee laxity.

Evaluation of Collaterals and Clot Burden Using Time-Resolved C-Arm Conebeam CT Angiography in the Angiography Suite: A Feasibility Study.

PubMed

Yang, P; Niu, K; Wu, Y; Struffert, T; Doerfler, A; Holter, P; Aagaard-Kienitz, B; Strother, C; Chen, G-H

2017-04-01

The assessment of collaterals and clot burden in patients with acute ischemic stroke provides important information about treatment options and clinical outcome. Time-resolved C-arm conebeam CT angiography has the potential to provide accurate and reliable evaluations of collaterals and clot burden in the angiographic suite. Experience with this technique is extremely limited, and feasibility studies are needed to validate this technique. Our purpose was to present such a feasibility study. Ten C-arm conebeam CT perfusion datasets from 10 subjects with acute ischemic stroke acquired before endovascular treatment were retrospectively processed to generate time-resolved conebeam CTA. From time-resolved conebeam CTA, 2 experienced readers evaluated the clot burden and collateral flow in consensus by using previously reported scoring systems and assessed the clinical value of this novel imaging technique independently. Interobserver agreement was analyzed by using the intraclass correlation analysis method. Clot burden and collateral flow can be assessed by using the commonly accepted scoring systems for all eligible cases. Additional clinical information (eg, the quantitative dynamic information of collateral flow) can be obtained from this new imaging technique. Two readers agreed that time-revolved C-arm conebeam CTA is the preferred method for evaluating the clot burden and collateral flow compared with other conventional imaging methods. Comprehensive evaluations of clot burden and collateral flow are feasible by using time-resolved C-arm conebeam CTA data acquired in the angiography suite. This technique further enriches the imaging tools in the angiography suite to enable a "one-stop- shop" imaging workflow for patients with acute ischemic stroke. © 2017 by American Journal of Neuroradiology.

The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis.

PubMed

Simons, K H; Aref, Z; Peters, H A B; Welten, S P; Nossent, A Y; Jukema, J W; Hamming, J F; Arens, R; de Vries, M R; Quax, P H A

2018-06-01

T cells have a distinctive role in neovascularization, which consists of arteriogenesis and angiogenesis under pathological conditions and vasculogenesis under physiological conditions. However, the role of co-stimulation in T cell activation in neovascularization has yet to be established. The aim of this study was to investigate the role T cell co-stimulation and inhibition in angiogenesis, arteriogenesis and vasculogenesis. Hind limb ischemia was induced by double ligation of the left femoral artery in mice and blood flow recovery was measured with Laser Doppler Perfusion Imaging in control, CD70 -/- , CD80/86 -/- , CD70/80/86 -/- and CTLA4 +/- mice. Blood flow recovery was significantly impaired in mice lacking CD70 compared to control mice, but was similar in CD80/86 -/- , CTLA4 +/- and control mice. Mice lacking CD70 showed impaired vasculogenesis, since the number of pre-existing collaterals was reduced as observed in the pia mater compared to control mice. In vitro an impaired capability of vascular smooth muscle cells (VSMC) to activate T cells was observed in VSMC lacking CD70. Furthermore, CD70 -/- , CD80/86 -/- and CD70/80/86 -/- mice showed reduced angiogenesis in the soleus muscle 10 days after ligation. Arteriogenesis was also decreased in CD70 -/- compared to control mice 10 and 28 days after surgery. The present study is the first to describe an important role for T cell activation via co-stimulation in angiogenesis, arteriogenesis and vasculogenesis, where the CD27-CD70 T cell co-stimulation pathway appears to be the most important co-stimulation pathway in pre-existing collateral formation and post-ischemic blood flow recovery, by arteriogenesis and angiogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Collateral transgression of planetary boundaries due to climate engineering by terrestrial carbon dioxide removal

NASA Astrophysics Data System (ADS)

Heck, Vera; Donges, Jonathan F.; Lucht, Wolfgang

2016-10-01

The planetary boundaries framework provides guidelines for defining thresholds in environmental variables. Their transgression is likely to result in a shift in Earth system functioning away from the relatively stable Holocene state. As the climate system is approaching critical thresholds of atmospheric carbon, several climate engineering methods are discussed, aiming at a reduction of atmospheric carbon concentrations to control the Earth's energy balance. Terrestrial carbon dioxide removal (tCDR) via afforestation or bioenergy production with carbon capture and storage are part of most climate change mitigation scenarios that limit global warming to less than 2 °C. We analyse the co-evolutionary interaction of societal interventions via tCDR and the natural dynamics of the Earth's carbon cycle. Applying a conceptual modelling framework, we analyse how the degree of anticipation of the climate problem and the intensity of tCDR efforts with the aim of staying within a "safe" level of global warming might influence the state of the Earth system with respect to other carbon-related planetary boundaries. Within the scope of our approach, we show that societal management of atmospheric carbon via tCDR can lead to a collateral transgression of the planetary boundary of land system change. Our analysis indicates that the opportunities to remain in a desirable region within carbon-related planetary boundaries only exist for a small range of anticipation levels and depend critically on the underlying emission pathway. While tCDR has the potential to ensure the Earth system's persistence within a carbon-safe operating space under low-emission pathways, it is unlikely to succeed in a business-as-usual scenario.

Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer.

PubMed

Denby, Charles M; Li, Rachel A; Vu, Van T; Costello, Zak; Lin, Weiyin; Chan, Leanne Jade G; Williams, Joseph; Donaldson, Bryan; Bamforth, Charles W; Petzold, Christopher J; Scheller, Henrik V; Martin, Hector Garcia; Keasling, Jay D

2018-03-20

Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.

12 CFR 223.42 - What covered transactions are exempt from the quantitative limits, collateral requirements, and...

Code of Federal Regulations, 2014 CFR

2014-01-01

... quantitative limits, collateral requirements, and low-quality asset prohibition? 223.42 Section 223.42 Banks... Provisions of Section 23A § 223.42 What covered transactions are exempt from the quantitative limits... quantitative limits of §§ 223.11 and 223.12, the collateral requirements of § 223.14, or the prohibition on the...

12 CFR 223.42 - What covered transactions are exempt from the quantitative limits, collateral requirements, and...

Code of Federal Regulations, 2013 CFR

2013-01-01

... quantitative limits, collateral requirements, and low-quality asset prohibition? 223.42 Section 223.42 Banks... Provisions of Section 23A § 223.42 What covered transactions are exempt from the quantitative limits... quantitative limits of §§ 223.11 and 223.12, the collateral requirements of § 223.14, or the prohibition on the...

12 CFR 221.108 - Effect of registration of stock subsequent to making of loan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... than the maximum loan value for the collateral specified in this part. (c) If the stock should become... increase the amount of the loan balance unless there was provided additional collateral having a maximum... value of the loan collateral or because of a decrease by the Board in the maximum loan value of the loan...

25 CFR 166.223 - Can I use a permit as collateral for a loan?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Can I use a permit as collateral for a loan? 166.223... PERMITS Permit Requirements Permit (leasehold) Mortgage § 166.223 Can I use a permit as collateral for a loan? We may approve a permit containing a provision that authorizes the permittee to encumber the...

Use of collateral information to improve LANDSAT classification accuracies

NASA Technical Reports Server (NTRS)

Strahler, A. H. (Principal Investigator)

1981-01-01

Methods to improve LANDSAT classification accuracies were investigated including: (1) the use of prior probabilities in maximum likelihood classification as a methodology to integrate discrete collateral data with continuously measured image density variables; (2) the use of the logit classifier as an alternative to multivariate normal classification that permits mixing both continuous and categorical variables in a single model and fits empirical distributions of observations more closely than the multivariate normal density function; and (3) the use of collateral data in a geographic information system as exercised to model a desired output information layer as a function of input layers of raster format collateral and image data base layers.

Anatomy and Biomechanics of the Finger Proximal Interphalangeal Joint.

PubMed

Pang, Eric Quan; Yao, Jeffrey

2018-05-01

A complete understanding of the normal anatomy and biomechanics of the proximal interphalangeal joint is critical when treating pathology of the joint as well as in the design of new reconstructive treatments. The osseous anatomy dictates the principles of motion at the proximal interphalangeal joint. Subsequently, the joint is stabilized throughout its motion by the surrounding proximal collateral ligament, accessory collateral ligament, and volar plate. The goal of this article is to review the normal anatomy and biomechanics of the proximal interphalangeal joint and its associated structures, most importantly the proper collateral ligament, accessory collateral ligament, and volar plate. Copyright © 2017 Elsevier Inc. All rights reserved.

Laser speckle contrast imaging of collateral blood flow during acute ischemic stroke

PubMed Central

Armitage, Glenn A; Todd, Kathryn G; Shuaib, Ashfaq; Winship, Ian R

2010-01-01

Collateral vasculature may provide an alternative route for blood flow to reach the ischemic tissue and partially maintain oxygen and nutrient support during ischemic stroke. However, much about the dynamics of stroke-induced collateralization remains unknown. In this study, we used laser speckle contrast imaging to map dynamic changes in collateral blood flow after middle cerebral artery occlusion in rats. We identified extensive anastomatic connections between the anterior and middle cerebral arteries that develop after vessel occlusion and persist for 24 hours. Augmenting blood flow through these persistent yet dynamic anastomatic connections may be an important but relatively unexplored avenue in stroke therapy. PMID:20517321

Self-, collateral- and clinician assessment of depression in persons with cognitive impairment

PubMed Central

Chopra, Mohit P.; Sullivan, Jan R.; Feldman, Zachary; Landes, Reid D.; Beck, Cornelia

2011-01-01

Objectives This investigation examined the associations between self-reports, collateral-source reports and a clinician’s diagnosis of depression in persons with cognitive impairment. Method Responses on the Geriatric Depression Scale – 15 (GDS-15) from 162 participants with a diagnosis of Mild Cognitive Impairment (n = 78) or Alzheimer’s Dementia and a Mini-Mental State score ≥15 (n = 84) were compared with both their collateral sources’ report on either the Neuropsychiatric Inventory Questionnaire (n = 93) and/or the collateral-source GDS-15 (n = 67), or a clinician’s diagnosis of Major Depression (MD). Results Significant differences were seen between self- versus collateral-source reports of depression in these participants. Participants’ reports of loss of interest (anhedonia) significantly increased the odds of disagreement with their collateral sources (OR = 3.78, 95% CI: 1.3–11.2) while reports of negative cognitions significantly decreased the odds of such a disagreement (OR = 0.31, 95% CI: 0.1–0.9). The symptom of anhedonia also showed the strongest association with the clinician’s diagnosis of MD. Conclusion A motivational symptom like loss of interest was seen to play an important role in depression experienced by those with cognitive impairment. PMID:19023719

The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity

PubMed Central

Harrison, Benjamin J.; Venkat, Gayathri; Lamb, James L.; Hutson, Tom H.; Drury, Cassa; Rau, Kristofer K.; Bunge, Mary Barlett; Mendell, Lorne M.; Gage, Fred H.; Johnson, Richard D.; Hill, Caitlin E.; Rouchka, Eric C.; Moon, Lawrence D.F.

2016-01-01

Growth of intact axons of noninjured neurons, often termed collateral sprouting, contributes to both adaptive and pathological plasticity in the adult nervous system, but the intracellular factors controlling this growth are largely unknown. An automated functional assay of genes regulated in sensory neurons from the rat in vivo spared dermatome model of collateral sprouting identified the adaptor protein CD2-associated protein (CD2AP; human CMS) as a positive regulator of axon growth. In non-neuronal cells, CD2AP, like other adaptor proteins, functions to selectively control the spatial/temporal assembly of multiprotein complexes that transmit intracellular signals. Although CD2AP polymorphisms are associated with increased risk of late-onset Alzheimer's disease, its role in axon growth is unknown. Assessments of neurite arbor structure in vitro revealed CD2AP overexpression, and siRNA-mediated knockdown, modulated (1) neurite length, (2) neurite complexity, and (3) growth cone filopodia number, in accordance with CD2AP expression levels. We show, for the first time, that CD2AP forms a novel multiprotein complex with the NGF receptor TrkA and the PI3K regulatory subunit p85, with the degree of TrkA:p85 association positively regulated by CD2AP levels. CD2AP also regulates NGF signaling through AKT, but not ERK, and regulates long-range signaling though TrkA+/RAB5+ signaling endosomes. CD2AP mRNA and protein levels were increased in neurons during collateral sprouting but decreased following injury, suggesting that, although typically considered together, these two adult axonal growth processes are fundamentally different. These data position CD2AP as a major intracellular signaling molecule coordinating NGF signaling to regulate collateral sprouting and structural plasticity of intact adult axons. SIGNIFICANCE STATEMENT Growth of noninjured axons in the adult nervous system contributes to adaptive and maladaptive plasticity, and dysfunction of this process may contribute to neurologic pathologies. Functional screening of genes regulated during growth of noninjured axons revealed CD2AP as a positive regulator of axon outgrowth. A novel association of CD2AP with TrkA and p85 suggests a distinct intracellular signaling pathway regulating growth of noninjured axons. This may also represent a novel mechanism of generating specificity in multifunctional NGF signaling. Divergent regulation of CD2AP in different axon growth conditions suggests that separate mechanisms exist for different modes of axon growth. CD2AP is the first signaling molecule associated with adult sensory axonal collateral sprouting, and this association may offer new insights for NGF/TrkA-related Alzheimer's disease mechanisms. PMID:27076424

Dendritic GIRK Channels Gate the Integration Window, Plateau Potentials, and Induction of Synaptic Plasticity in Dorsal But Not Ventral CA1 Neurons

PubMed Central

2017-01-01

Studies comparing neuronal activity at the dorsal and ventral poles of the hippocampus have shown that the scale of spatial information increases and the precision with which space is represented declines from the dorsal to ventral end. These dorsoventral differences in neuronal output and spatial representation could arise due to differences in computations performed by dorsal and ventral CA1 neurons. In this study, we tested this hypothesis by quantifying the differences in dendritic integration and synaptic plasticity between dorsal and ventral CA1 pyramidal neurons of rat hippocampus. Using a combination of somatic and dendritic patch-clamp recordings, we show that the threshold for LTP induction is higher in dorsal CA1 neurons and that a G-protein-coupled inward-rectifying potassium channel mediated regulation of dendritic plateau potentials and dendritic excitability underlies this gating. By contrast, similar regulation of LTP is absent in ventral CA1 neurons. Additionally, we show that generation of plateau potentials and LTP induction in dorsal CA1 neurons depends on the coincident activation of Schaffer collateral and temporoammonic inputs at the distal apical dendrites. The ventral CA1 dendrites, however, can generate plateau potentials in response to temporally dispersed excitatory inputs. Overall, our results highlight the dorsoventral differences in dendritic computation that could account for the dorsoventral differences in spatial representation. SIGNIFICANCE STATEMENT The dorsal and ventral parts of the hippocampus encode spatial information at very different scales. Whereas the place-specific firing fields are small and precise at the dorsal end of the hippocampus, neurons at the ventral end have comparatively larger place fields. Here, we show that the dorsal CA1 neurons have a higher threshold for LTP induction and require coincident timing of excitatory synaptic inputs for the generation of dendritic plateau potentials. By contrast, ventral CA1 neurons can integrate temporally dispersed inputs and have a lower threshold for LTP. Together, these dorsoventral differences in the threshold for LTP induction could account for the differences in scale of spatial representation at the dorsal and ventral ends of the hippocampus. PMID:28280255

Dendritic GIRK Channels Gate the Integration Window, Plateau Potentials, and Induction of Synaptic Plasticity in Dorsal But Not Ventral CA1 Neurons.

PubMed

Malik, Ruchi; Johnston, Daniel

2017-04-05

Studies comparing neuronal activity at the dorsal and ventral poles of the hippocampus have shown that the scale of spatial information increases and the precision with which space is represented declines from the dorsal to ventral end. These dorsoventral differences in neuronal output and spatial representation could arise due to differences in computations performed by dorsal and ventral CA1 neurons. In this study, we tested this hypothesis by quantifying the differences in dendritic integration and synaptic plasticity between dorsal and ventral CA1 pyramidal neurons of rat hippocampus. Using a combination of somatic and dendritic patch-clamp recordings, we show that the threshold for LTP induction is higher in dorsal CA1 neurons and that a G-protein-coupled inward-rectifying potassium channel mediated regulation of dendritic plateau potentials and dendritic excitability underlies this gating. By contrast, similar regulation of LTP is absent in ventral CA1 neurons. Additionally, we show that generation of plateau potentials and LTP induction in dorsal CA1 neurons depends on the coincident activation of Schaffer collateral and temporoammonic inputs at the distal apical dendrites. The ventral CA1 dendrites, however, can generate plateau potentials in response to temporally dispersed excitatory inputs. Overall, our results highlight the dorsoventral differences in dendritic computation that could account for the dorsoventral differences in spatial representation. SIGNIFICANCE STATEMENT The dorsal and ventral parts of the hippocampus encode spatial information at very different scales. Whereas the place-specific firing fields are small and precise at the dorsal end of the hippocampus, neurons at the ventral end have comparatively larger place fields. Here, we show that the dorsal CA1 neurons have a higher threshold for LTP induction and require coincident timing of excitatory synaptic inputs for the generation of dendritic plateau potentials. By contrast, ventral CA1 neurons can integrate temporally dispersed inputs and have a lower threshold for LTP. Together, these dorsoventral differences in the threshold for LTP induction could account for the differences in scale of spatial representation at the dorsal and ventral ends of the hippocampus. Copyright © 2017 the authors 0270-6474/17/373940-16$15.00/0.

Nano-CuO impairs spatial cognition associated with inhibiting hippocampal long-term potentiation via affecting glutamatergic neurotransmission in rats.

PubMed

Li, Xiaoliang; Sun, Wei; An, Lei

2018-06-01

Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0.5 mg/kg/day for 2 weeks. The Morris water maze (MWM) test was employed to evaluate learning and memory. The long-term potentiation (LTP) from Schaffer collaterals to the hippocampal CA1 region, and the effects of nano-CuO on synases were recorded in the hippocampal CA1 neurons of rats. MWM test showed that learning and memory abilities were impaired significantly by nano-CuO ( p < 0.05). The LTP test demonstrated that the field excitatory postsynaptic potential (fEPSP) slopes were significantly lower in nano-CuO-treated groups compared with the control group ( p < 0.01). Furthermore, the data of whole-cell patch-clamp experiments showed that nano-CuO markedly depressed the frequencies of both spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs), indicating an effect of nano-CuO on inhibiting the release frequency of glutamate presynapticly ( p < 0.01). Meanwhile, the amplitudes of both sEPSC and mEPSC were significantly reduced in nano-CuO-treated animals, which suggested that the effect of nano-CuO modulates postsynaptic receptor kinetics ( p < 0.01). Paired pulse facilitation (PPF) ( p < 0.05) and the expression of NR2A, but not NR2B, of N-methyl-d-aspartate (NMDA) subunits ( p < 0.05), were decreased significantly. In conclusion, nano-CuO impaired glutamate transmission presynapticly and postsynapticly, which may contribute importantly to diminished LTP and other induced cognitive deficits.

Transgenic Mice with Increased Astrocyte Expression of IL-6 Show Altered Effects of Acute Ethanol on Synaptic Function

PubMed Central

Hernandez, Ruben V.; Puro, Alana C.; Manos, Jessica C.; Huitron-Resendiz, Salvador; Reyes, Kenneth C.; Liu, Kevin; Vo, Khanh; Roberts, Amanda J.; Gruol, Donna L.

2015-01-01

A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including persistent changes in CNS function that contribute to cognitive dysfunction and the development of alcohol dependence. PMID:26707655

GABAergic contributions to gating, timing, and phase precession of hippocampal neuronal activity during theta oscillations.

PubMed

Cutsuridis, Vassilis; Hasselmo, Michael

2012-07-01

Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra- and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo-axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum-moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate-keeper modulating the spatial memory flow to the PC distal dendrites in a frequency-dependent manner. A mechanism for spike-timing-dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories as well as in the generation and maintenance of theta phase precession of pyramidal cells (place cells) in CA1. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical computations in the hippocampus and medial septum. Copyright © 2011 Wiley Periodicals, Inc.

Change in collateral ligament length and tibiofemoral movement following joint line variation in TKA.

PubMed

Lin, Kun-Jhih; Wei, Hung-Wen; Huang, Chang-Hung; Liu, Yu-Liang; Chen, Wen-Chuan; McClean, Colin Joseph; Cheng, Cheng-Kung

2016-08-01

The primary intent of total knee arthroplasty is the restoration of normal knee kinematics, with ligamentous constraint being a key influential factor. Displacement of the joint line may lead to alterations in ligament attachment sites relative to knee flexion axis and variance of ligamentous constraints on tibiofemoral movement. This study aimed to investigate collaterals strains and tibiofemoral kinematics with different joint line levels. A previously validated knee model was employed to analyse the change in length of the collateral ligaments and tibiofemoral motion during knee flexion. The models shifted the joint line by 3 and 5 mm both proximally and distally from the anatomical level. The data were captured from full extension to flexion 135°. The elevated joint line revealed a relative increase in distance between ligament attachments for both collateral ligaments in comparison with the anatomical model. Also, tibiofemoral movement decreased with an elevation in the joint line. Conversely, lowering the joint line led to a significant decrease in distance between ligament attachments, but greater tibiofemoral motion. Elevation of the joint line would strengthen the capacity of collateral ligaments for knee motion constraint, whereas a distally shifted joint line might have the advantage of improving tibiofemoral movement by slackening the collaterals. It implies that surgeons can appropriately change the joint line position in accordance with patient's requirement or collateral tensions. A lowered joint line level may improve knee kinematics, whereas joint line elevation could be useful to maintain knee stability. V.

In vivo Length Change Patterns of the Medial and Lateral Collateral Ligaments along the Flexion Path of the Knee

PubMed Central

Hosseini, Ali; Qi, Wei; Tsai, Tsung-Yuan; Liu, Yujie; Rubash, Harry; Li, Guoan

2014-01-01

Purpose The knowledge of the function of the collateral ligaments – i.e., superficial medial collateral ligament (sMCL), deep medial collateral ligament (dMCL) and lateral collateral ligament (LCL) – in the entire range of knee flexion is important for soft tissue balance during total knee arthroplasty. The objective of this study was to investigate the length changes of different portions (anterior, middle and posterior) of the sMCL, dMCL and LCL during in vivo weightbearing flexion from full extension to maximal knee flexion. Methods Using a dual fluoroscopic imaging system eight healthy knees were imaged while performing a lunge from full extension to maximal flexion. The length changes of each portion of the collateral ligaments were measured along the flexion path of the knee. Results All anterior portions of the collateral ligaments were shown to have increasing length with flexion except that of the sMCL which showed a reduction in length at high flexion. The middle portions showed minimal change in lengths except that of the sMCL which showed a consistent reduction in length with flexion. All posterior portions showed reduction in lengths with flexion. Conclusions These data indicated that every portion of the ligaments may play important roles in knee stability at different knee flexion range. The soft tissue releasing during TKA may need to consider the function of the ligament portions along the entire flexion path including maximum flexion. PMID:25239504

Effects of an Air-Powder Abrasive Device When Used during Periodontal Flap Surgery in Dogs.

DTIC Science & Technology

1983-01-01

instru- ments, ultrasonic devices, air driven reciprocating hand- pieces, and air driven rotary handpieces (Schaffer, 1967). None of these techniques...system, the Prophy-Jet Mark IV C-100 , may be an alternative to conventional mechanical and chemical methods of detoxifying roots. The handpiece is...electric current and uses inlet air pressure of 65 to 100 p.s.i. and inlet water pressure of 25 to 60 p.s.i. The handpiece propels particles of the

Horse Hoof Protectors

NASA Technical Reports Server (NTRS)

2004-01-01

Power Pads, shown here, were designed to support and cushion horses' hooves while walking, rurning, and jumping, thus reducing the risk of injury. The pads utilize magnets implanted in the pads to increase blood circulation, not only reducing the chance of injury, but also speeding up the healing process if an injury does occur. Marshall Space Flight Center materials engineer Deborah Dianne Schmidt and materials technician Anthony Schaffer contributed to the design by providing fatigue stress analysis to the prototypes, thus helping determine the best configuration and maximum durability.

Benefit from NASA

NASA Image and Video Library

2004-04-15

Power Pads, shown here, were designed to support and cushion horses' hooves while walking, rurning, and jumping, thus reducing the risk of injury. The pads utilize magnets implanted in the pads to increase blood circulation, not only reducing the chance of injury, but also speeding up the healing process if an injury does occur. Marshall Space Flight Center materials engineer Deborah Dianne Schmidt and materials technician Anthony Schaffer contributed to the design by providing fatigue stress analysis to the prototypes, thus helping determine the best configuration and maximum durability.

Unusual collateral vessel from right subclavian vein to left atrium, a rare complication of superior vena cava obstruction.

PubMed

Parsaee, Mozhgan; Pouraliakbar, Hamidreza; Ghadrdoost, Behshid; Moosavi, Jamal; Behjati, Mohaddeseh

2018-06-10

The most commonly reported collateral systems in the setting of superior vena cava obstruction are azygos venous system, vertebral venous system, external and internal thoracic venous system based on McLntire and Sykes classification. A 49-year-old female with renal disease complained dyspnea on exertion. Transesophageal echocardiography showed significant mitral annular calcification, large multi-lobulated mass at posterior aspect of RA, and complete obstruction of superior vena cava by thrombus formation. Computed tomography angiography showed a collateral vein to the left atrium (LA) roof. This case report is the first one which shows development of collateral vein from right subclavian to LA. © 2018 Wiley Periodicals, Inc.

CUDA-based acceleration of collateral filtering in brain MR images

NASA Astrophysics Data System (ADS)

Li, Cheng-Yuan; Chang, Herng-Hua

2017-02-01

Image denoising is one of the fundamental and essential tasks within image processing. In medical imaging, finding an effective algorithm that can remove random noise in MR images is important. This paper proposes an effective noise reduction method for brain magnetic resonance (MR) images. Our approach is based on the collateral filter which is a more powerful method than the bilateral filter in many cases. However, the computation of the collateral filter algorithm is quite time-consuming. To solve this problem, we improved the collateral filter algorithm with parallel computing using GPU. We adopted CUDA, an application programming interface for GPU by NVIDIA, to accelerate the computation. Our experimental evaluation on an Intel Xeon CPU E5-2620 v3 2.40GHz with a NVIDIA Tesla K40c GPU indicated that the proposed implementation runs dramatically faster than the traditional collateral filter. We believe that the proposed framework has established a general blueprint for achieving fast and robust filtering in a wide variety of medical image denoising applications.

The Autophagy-Senescence Connection in Chemotherapy: Must Tumor Cells (Self) Eat Before They Sleep?

PubMed Central

Goehe, Rachel W.; Di, Xu; Sharma, Khushboo; Bristol, Molly L.; Henderson, Scott C.; Valerie, Kristoffer; Rodier, Francis; Davalos, Albert R.

2012-01-01

Exposure of MCF-7 breast tumor cells or HCT-116 colon carcinoma cells to clinically relevant concentrations of doxorubicin (Adriamycin; Farmitalia Research Laboratories, Milan, Italy) or camptothecin results in both autophagy and senescence. To determine whether autophagy is required for chemotherapy-induced senescence, reactive oxygen generation induced by Adriamycin was suppressed by N-acetyl cysteine and glutathione, and the induction of ataxia telangiectasia mutated, p53, and p21 was modulated pharmacologically and/or genetically. In all cases, autophagy and senescence were collaterally suppressed. The close association between autophagy and senescence indicated by these experiments reflects their collateral regulation via common signaling pathways. The potential relationship between autophagy and senescence was further examined through pharmacologic inhibition of autophagy with chloroquine and 3-methyl-adenine and genetic ablation of the autophagy-related genes ATG5 and ATG7. However, inhibition of autophagy by pharmacological and genetic approaches could not entirely abrogate the senescence response, which was only reduced and/or delayed. Taken together, our findings suggest that autophagy and senescence tend to occur in parallel, and furthermore that autophagy accelerates the development of the senescent phenotype. However, these responses are not inexorably linked or interdependent, as senescence can occur when autophagy is abrogated. PMID:22927544

The effects of collateral consequences of criminal involvement on employment, use of Temporary Assistance for Needy Families, and health

PubMed Central

Kneipp, Shawn M.

2017-01-01

Criminal convictions are often associated with collateral consequences that limit access to the forms of employment and social services on which disadvantaged women most frequently rely – regardless of the severity of the offense. These consequences may play an important role in perpetuating health disparities by socioeconomic status and gender. We examined the extent to which research studies to date have assessed whether a criminal conviction might influence women’s health by limiting access to Temporary Assistance for Needy Families (TANF) and employment, as a secondary, or “collateral” criminal conviction-related consequence. We reviewed 434 peer-reviewed journal articles retrieved from three electronic article databases and 197 research reports from three research organizations. Two reviewers independently extracted data from each eligible article or report using a standardized coding scheme. Of the sixteen eligible studies included in the review, most were descriptive. None explored whether receiving TANF modified health outcomes, despite its potential to do so. Researchers to date have not fully examined the causal pathways that could link employment, receiving TANF, and health, especially for disadvantaged women. Future research is needed to address this gap and to understand better the potential consequences of the criminal justice system involvement on the health of this vulnerable population. PMID:25905904

Periprocedural ischaemia during recanalisation of chronic total coronary occlusions: the influence of the transcollateral retrograde approach.

PubMed

Werner, Gerald S; Coenen, Anja; Tischer, Karl-Heinz

2014-11-01

Percutaneous coronary intervention for chronic total coronary occlusions (CTO) becomes increasingly more complex with the transcollateral retrograde approach. This study assesses the effect of the retrograde approach on markers of ischaemia and clinical events. Four hundred and ninety-two consecutive procedures in 392 patients were prospectively evaluated. Before and within 18-24 hours after the PCI creatine kinase (CK) and cardiac troponin I (cTnI) were obtained. A CK increase of greater than three times the upper limit of normal (ULN) was considered a periprocedural MI. Patients with initially elevated cTnI were excluded. In 106 patients with a retrograde wire passage of the septal collaterals, the incidence of a CK or TnI increase was higher as compared to the antegrade group. Patients with septal dilatation or passage of a dilatation catheter (Corsair) showed the highest cTnI. There was no difference in cardiac death or cerebral complications between the groups with antegrade and retrograde approach within the first 30 days. Complex retrograde recanalisation procedures for CTOs lead to an increased periprocedural ischaemic burden, most likely due to obstruction of the collateral pathway, and to the increased plaque burden of complex lesions treated with the retrograde approach.

Disclosure of Federal Acquisition Records.

DTIC Science & Technology

1981-05-24

Parties. .. .. .. . ... .. ....... 170 Collateral Estoppel . .. ......... .. ... ...... 171 Basis for Relief and Scope ofReview .. .. .. ..... 1741Burden of...grounds to a decision by a co-ordinate court with which he disagreed is unworthy of comment. 𔄁 3 (2) Collateral estoppel --"If the FOIA applicant has...documents.ś 3 7 The Supreme Court did not discuss stare decisis, or collateral 1 estoppel , or comity, as had the D,C. Circuit Court of Appeals; instead

31 CFR 380.3 - What collateral may I pledge if I am a Treasury Tax and Loan depositary under 31 CFR part 203...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What collateral may I pledge if I am a Treasury Tax and Loan depositary under 31 CFR part 203, and what value will you assign to it? 380...) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT COLLATERAL ACCEPTABILITY AND...

Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke.

PubMed

Ma, Junqiang; Ma, Yonglie; Dong, Bin; Bandet, Mischa V; Shuaib, Ashfaq; Winship, Ian R

2017-08-01

Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo. LSCI and TPLSM revealed that RIPerC augmented collateral flow into distal MCA segments. Notably, while control rats exhibited an initial dilation followed by a progressive narrowing of pial arterioles 60 to 150-min post-MCAo (constricting to 80-90% of post-MCAo peak diameter), this constriction was prevented or reversed by RIPerC (such that vessel diameters increased to 105-110% of post-MCAo, pre-RIPerC diameter). RIPerC significantly reduced early ischemic damage measured 6 h after stroke onset. Thus, prevention of collateral collapse via RIPerC is neuroprotective and may facilitate other protective or recanalization therapies by improving blood flow in penumbral tissue.

Detection of cerebral collateral circulation with Tc-99m HMPAO radionuclide angiography in cerebrovascular diseases: Delayed filling-in sign

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

Ueno, K.

1994-05-01

In patients with internal carotid and major cerebral arterial obstructions, it is clinically important to know the presence of collateral circulation. However, this information is not available from Tc-99m HMPAO perfusion SPECT alone. To investigate the usefulness of Tc-99m HMPAO radionuclide angiography (RNA) in the diagnosis of collaterals, we retrospectively studied 39 patients (pts) cerebrovascular diseases (CVD) with HMPAO RNA and SPECT. Contrast angiography was done on all pts. Of these, 11 internal carotid artery (ICA), 1 anterior cerebral artery (ACA), and 3 middle cerebral artery (MCA) obstructions were found angiographically. Non- or decreased visualization of ICA was found inmore » 11 of 11 pts of ICA obstruction. In 1 pt of ICA obstruction, the collaterals were directly visualized with RNA. Early perfusion deficient area with delayed filling-in with Tc-HMPAO was found in 7 of 11 pts of ICA, 1 of 1 pt of ACA, and 2 of 3 pts of MCA obstructions. In all pts with the delayed filling-in sign on RNA, collateral circulations were confirmed angiographically. We conclude that the delayed filling-in of Tc-HMPAO is a useful sign of collateral circulation in the CVD pts.« less

Resiliency and collateral learning in science in some students of cree ancestry

NASA Astrophysics Data System (ADS)

Sutherland, Dawn

2005-07-01

In the context of schooling, resiliency refers to the ability to thrive academically despite adverse circumstances. In this study the relationship between academic resilience and student's collateral learning is explored in 20 students of Cree ancestry. The individual resilience of each student was examined by identifying protective factors for school leaving within the microsystem of each student's ecological framework. Student responses to questions related to motivation and engagement were ranked. In addition, students' perception of the influence of family and peers on individual attributes toward schooling was ranked.To gain insight into the collateral learning aspects of science learning in Cree students, the participants in this study were asked to reflect on their learning strategies through the use of critical incidents. The relationship between collateral learning and resiliency was also explored.This study found that students possessing a greater number of protective factors were more likely to learn science in a way described by Jegede's collateral learning theory. Responses to critical incidents indicate some Cree students hold at least two sources of knowledge to explain some science concepts and therefore may adopt a collateral learning strategy. The importance these students place on earned or experiential knowledge is evident in the interviews. Some suggestions for classroom instruction are offered in conclusion.

Influence of angiographic collateral circulation on myocardial perfusion in patients with chronic total occlusion of a single coronary artery and no prior myocardial infarction.

PubMed

Aboul-Enein, Fatma; Kar, Saibal; Hayes, Sean W; Sciammarella, Maria; Abidov, Aiden; Makkar, Raj; Friedman, John D; Eigler, Neal; Berman, Daniel S

2004-06-01

The functional role of various angiographic grades for coronary collaterals remains controversial. The aim of this study was to assess the influence of the Rentrop angiographic grading of coronary collaterals on myocardial perfusion in patients with single-vessel chronic total occlusion (CTO) and no prior myocardial infarction (MI). The study included 56 patients with single-vessel CTO and no prior MI who underwent rest-stress myocardial perfusion SPECT and coronary angiography within 6 mo. All patients had angiographic evidence of coronary collaterals. Patients were divided according to the Rentrop classification: Group I had grade 1 or 2 (n = 25) and group II had grade 3 collaterals (n = 31). Group I had a higher frequency of resting regional wall motion abnormalities on left ventriculography (52.6% vs. 19.2% [P = 0.019]). The mean perfusion scores of the overall population showed severe and extensive stress perfusion defects (summed stress score of 14.1 +/- 7.1 and summed difference score of 12.9 +/- 6.9) but minimal resting perfusion defects (summed rest score of 1.0 +/- 2.7). No perfusion scores differed between the 2 groups. The perfusion findings suggested that chronic stunning rather than hibernation is the principal cause of regional wall motion abnormalities in these patients. In the setting of single-vessel CTO and no prior MI, coronary collaterals appear to protect against resting perfusion defects. Excellent angiographic collaterals may prevent resting regional wall motion abnormalities but do not appear to protect against stress-induced perfusion defects.

The "moving valgus stress test" for medial collateral ligament tears of the elbow.

PubMed

O'Driscoll, Shawn W M; Lawton, Richard L; Smith, Adam M

2005-02-01

The diagnosis of a painful partial tear of the medial collateral ligament in overhead-throwing athletes is challenging, even for experienced elbow surgeons and despite the use of sophisticated imaging techniques. The "moving valgus stress test" is an accurate physical examination technique for diagnosis of medial collateral ligament attenuation in the elbow. Cohort study (diagnosis); Level of evidence, 2. Twenty-one patients underwent surgical intervention for medial elbow pain due to medial collateral ligament insufficiency or other abnormality of chronic valgus overload, and they were assessed preoperatively with an examination called the moving valgus stress test. To perform the moving valgus stress test, the examiner applies and maintains a constant moderate valgus torque to the fully flexed elbow and then quickly extends the elbow. The test is positive if the medial elbow pain is reproduced at the medial collateral ligament and is at maximum between 120 degrees and 70 degrees. The moving valgus stress test was highly sensitive (100%, 17 of 17 patients) and specific (75%, 3 of 4 patients) when compared to assessment of the medial collateral ligament by surgical exploration or arthroscopic valgus stress testing. The mean shear range (ie, the arc within which pain was produced with the moving valgus stress test) was 120 degrees to 70 degrees. The mean angle at which pain was at a maximum was 90 degrees of elbow flexion. The moving valgus stress test is an accurate physical examination technique that, when performed and interpreted correctly, is highly sensitive for medial elbow pain arising from the medial collateral ligament.

Insights into coronary collateral formation from a novel porcine semiacute infarction model.

PubMed

Krackhardt, Florian; Harnoss, Jonathan M; Waliszewski, Matthias W; Ritter, Zully; Granzow, Susanne; Felsenberg, Dieter; Neumann, Konrad; Lerman, Lilian O; Hillmeister, Philipp; Gebker, Rolf; Paetsch, Ingo; Riediger, Fabian; Bramlage, Peter; Buschmann, Ivo R

2018-03-01

For patients with severe ischemic heart disease, complete revascularization by a percutaneous coronary intervention or coronary artery bypass grafting is often not achieved and may still cause residual angina. In case of progressive coronary artery occlusions, therapeutic arteriogenesis constitutes a promising strategy for increasing blood supply to the ischemic myocardium. Whether the formation of collaterals in the hypofused myocardium is angiogenetic in nature or based on preformed coronary artery anastomoses remains debatable. The objectives of this research were (i) the development of an appropriate research methodology to study a humanoid animal semiacute infarction model with low mortality and (ii) to answer the question of whether collateral revascularization follows a pre-existing 'blueprint'. A porcine model was chosen in which a step-wise vessel occlusion was performed by implantation of a copper stent into the distal left anterior descending artery. Vessel occlusion and collateral development were confirmed in vivo every 14 days up to day 56 by repeated coronary angiography and myocardial perfusion measurement using cardiac MRI. After the completion of the in-vivo imaging studies, animals were euthanized and collateral growth was evaluated using microcomputer tomography. Our porcine model of semiacute noninvasive coronary artery occlusion confirmed the existence of preformed coronary anastomoses and the proliferation of functional vessels in hypoperfused myocardium. Repetitive intra-animal MRIs showed the functional impact of these growing collaterals. The confirmation of preformed coronary anastomoses during the process of collateralization (natural bypasses) offers a preclinical avenue to carry out arteriogenetic pharmaceutical research in patients with ischemic heart disease.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

PubMed

Wang, Li; Lu, Min-Jie; Feng, Lei; Wang, Juan; Fang, Wei; He, Zuo-Xiang; Dou, Ke-Fei; Zhao, Shi-Hua; Yang, Min-Fu

2018-03-07

The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18 F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99m Tc-sestamibi and 18 F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18 F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

Impact of the origin of the collateral feeding donor artery on short-term mortality in ST-elevation myocardial infarction with comorbid chronic total occlusion.

PubMed

Fujii, Toshiharu; Sakai, Katsuaki; Nakano, Masataka; Ohno, Yohei; Nakazawa, Gaku; Shinozaki, Norihiko; Matsukage, Takashi; Yoshimachi, Fuminobu; Ikari, Yuji

2016-09-01

Patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD) have higher mortality, especially with comorbid chronic total occlusion (CTO). The origin of collateral flow to the CTO segment has not been studied in regard to short-term mortality. This study examined the impact of collateral feeding donor arteries from an infarct-related artery (IRA) or non-IRA to the comorbid CTO segment in regard to STEMI short-term mortality. Data from 760 consecutive STEMI patients who underwent primary percutaneous coronary intervention were obtained retrospectively from medical records. The number of vessels involved and origin of the collateral feeding donor artery were evaluated using angiograms from the primary percutaneous coronary intervention. The study population was divided into patients with: single-vessel disease (SVD) (n=483), MVD without CTO (n=208), and MVD with CTO (n=64). All CTO segments had collateral flow from an IRA (n=23) or non-IRA (n=46). All-cause mortality (30-day) was analyzed. Compared to SVD and MVD without CTO, MVD with comorbid CTO had a higher mortality (5.4% vs. 15.9% vs. 24.6%, P<0.0001, respectively). Of patients with CTO, those with collateral flow from the IRA had significantly higher mortality than the non-IRA group (52.2% vs. 10.9%, P<0.0001). Collateral flow from the IRA was extracted as an independent predictor associated with 30-day all-cause mortality using a multivariate Cox proportional hazards model (hazard ratio 4.71, 95% confidence interval 1.60-14.2, P=0.0005). The origin of the collateral donor artery from the IRA had an impact on short-term mortality in STEMI patients with comorbid CTO lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

PubMed

Breda, Vitor; Rovaris, Diego Luiz; Vitola, Eduardo Schneider; Mota, Nina Roth; Blaya-Rocha, Paula; Salgado, Carlos Alberto Iglesias; Victor, Marcelo Moraes; Picon, Felipe Almeida; Karam, Rafael Gomes; Silva, Katiane Lilian; Rohde, Luis Augusto; Bau, Claiton Henrique Dotto; Grevet, Eugenio Horacio

2016-06-01

In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Vasoresponsiveness of collateral vessels in the rat hindlimb: influence of training.

PubMed

Colleran, Patrick N; Li, Zeyi; Yang, Hsiao T; Laughlin, M Harold; Terjung, Ronald L

2010-04-15

Exercise training is known to be an effective means of improving functional capacity and quality of life in patients with peripheral arterial insufficiency (PAI). However, the specific training-induced physiological adaptations occurring within collateral vessels remain to be clearly defined. The purpose of this study was to determine the effect of exercise training on vasomotor properties of isolated peripheral collateral arteries. We hypothesized that daily treadmill exercise would improve the poor vasodilatory capacity of collateral arteries isolated from rats exposed to surgical occlusion of the femoral artery. Following femoral artery ligation, animals were either kept sedentary or exercise trained daily for a period of 3 weeks. Hindlimb collateral arteries were then isolated, cannulated and pressurized via hydrostatic reservoirs to an intravascular pressure of either 45 or 120 cmH(2)O. Non-occluded contralateral vessels of the sedentary animals served as normal Control. Vasodilatory responses to acetylcholine (ACh; 1 x 10(9)-1 x 10(5)m) and sodium nitroprusside (SNP; 1 x 10(9)-1 x 10(4)m), constrictor responses to phenylephrine (PE; 1 x 10(9)-1 x 10(4)m), and flow-induced vasodilatation were determined. Endothelium-mediated vasodilatation responses were significantly greater to either ACh (P < 0.02) or intravascular flow (P < 0.001) in collateral arteries of trained rats. Neither blockade of cyclooxygenase with indomethacin (Indo; 5 microm) nor blockade of endothelial nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microm) eliminated this ACh- or flow-induced vasodilatation. The depressed vasodilatory response to SNP caused by vascular occlusion was reversed with training. These data indicate that exercise training improves endothelium-mediated vasodilatory capacity of hindlimb collateral arteries, apparently by enhanced production of the putative endothelium-derived hyperpolarizing factor(s). If these findings were applicable to patients with PAI, they could contribute to an improved collateral vessel function and enhance exercise tolerance during routine physical activity.

7 CFR 1779.48 - Collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.48 Collateral. (a) Lender..., water rights, buildings, machinery, equipment, accounts receivable, contracts, cash, or other accounts...

Chronic thalidomide administration enhances vascular responsiveness to vasopressin in portal-systemic collaterals of bile duct-ligated rats.

PubMed

Chang, Ching-Chih; Wang, Sun-Sang; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Lee, Jing-Yi; Chen, Yi-Chou; Lee, Shou-Dong

2009-05-01

Arginine vasopressin (AVP) controls gastroesophageal variceal bleeding, partly due to its vasoconstrictive effect on portal-systemic collaterals. It has been shown that chronic thalidomide treatment decreases portal pressure, attenuates hyperdynamic circulation and inhibits vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-alpha in partially portal vein-ligated rats. This study investigated the effects of chronic thalidomide treatment on portal-systemic collateral vascular responsiveness to AVP in common bile duct-ligated (CBDL) cirrhotic rats. In the first series, CBDL-induced cirrhotic rats received thalidomide (50 mg/kg/day orally) or distilled water (control) from the 35th to 42nd day after ligation. On the 43rd day after ligation, the body weight, mean arterial pressure, portal pressure, and heart rate were measured. An in situ collateral vascular perfusion model was used to obtain the cumulative concentration-response curves of collateral vessels to AVP (10(-10) to 3 x 10(-7) M). Plasma levels of VEGF and TNF-alpha were measured, and expressions of VEGF and TNF-alpha mRNA in the left adrenal veins were also determined. In the second series, the cumulative concentration-response curves of collateral vessels to AVP in CBDL rats with or without thalidomide (10(-5) M) preincubation in the perfusate were obtained. The thalidomide and control groups were not significantly different in terms of heart rate, mean arterial pressure and portal pressure (p > 0.05). The collateral vascular perfusion pressure change to AVP was significantly enhanced at 10(-8) M after thalidomide treatment (p = 0.041). Compared with the control group, thalidomide-treated rats had significantly lower plasma VEGF levels (p < 0.001), accompanied by an insignificant reduction in plasma TNF-alpha levels (p > 0.05). The expressions of VEGF and TNF-alpha mRNA in the left adrenal veins of thalidomide-treated CBDL rats were not significantly changed compared with those of the control group. In addition, thalidomide did not significantly elicit changes in vascular responsiveness to AVP in collateral vessels of CBDL rats when it was added into the perfusate. In cirrhotic rats, chronic thalidomide treatment improves the portal-systemic collateral vascular responsiveness to AVP, which was partly related to VEGF inhibition.

Exercise training increases basal tone in arterioles distal to chronic coronary occlusion

PubMed Central

Heaps, Cristine L.; Mattox, Mildred L.; Kelly, Katherine A.; Meininger, Cynthia J.; Parker, Janet L.

2014-01-01

Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (~150 µm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound (P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition (Nω-nitro-l-arginine methylester; 100 µM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium. PMID:16243909

When collateral supply is accounted for epicardial stenosis does not increase microvascular resistance.

PubMed

Layland, Jamie; MacIsaac, Andrew I; Burns, Andrew T; Somaratne, Jithendra B; Leitl, George; Whitbourn, Robert J; Wilson, Andrew M

2012-02-01

The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis. Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89, P=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06, P<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89, P=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78, P=0.42). When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.

Coronary Collateral Growth—Back to the Future

PubMed Central

Chilian, William M.; Penn, Marc S.; Pung, Yuh Fen; Dong, Feng; Mayorga, Maritza; Ohanyan, Vahagn; Logan, Suzanna; Yin, Liya

2012-01-01

The coronary collateral circulation is critically important as an adaptation of the heart to prevent the damage from ischemic insults. In their native state, collaterals in the heart would be classified as part of the microcirculation, existing as arterial-arterial anastomotic connections in the range of 30 to 100 μM in diameter. However, these vessels also show a propensity to remodel into components of the macrocirculation and can become arteries larger than a 1000 μM in diameter. This process of outward remodelling is critically important in the adaptation of the heart to ischemia because the resistance to blood flow is inversely related to the fourth power of the diameter of the vessel. Thus, an expansion of a vessel from 100 to 1000 μM would reduce resistance (in this part of the circuit) to a negligible amount and enable delivery of flow to the region at risk. Our goal in this review is to highlight the voids in understanding this adaptation to ischemia—the growth of the coronary collateral circulation. In doing so we discuss the controversies and unknown aspects of the causal factors that stimulate growth of the collateral circulation, the role of genetics, and the role of endogenous stem and progenitor cells in the context of the normal, physiological situation and under more pathological conditions of ischemic heart disease or with some of the underlying risk factors, e.g., diabetes. The major conclusion of this review is that there are many gaps in our knowledge of coronary collateral growth and this knowledge is critical before the potential of stimulating collateralization in the hearts of patients can be realized. PMID:22210280

Color Doppler Sonographic and Cadaveric Study of the Arterial Vascularity of the Lateral Upper Arm Flap.

PubMed

Sun, Ruimei; Ding, Yu; Sun, Chuanzheng; Li, Xiaojiang; Wang, Jinde; Li, Lei; Yang, Jie; Ren, Yanxin; Zhong, Zhaoming

2016-04-01

To determine the importance of adequate preoperative assessment with color Doppler sonography to assist in the successful transfer of lateral upper arm flaps by studying the lateral upper arm flap with color Doppler sonography and analyzing the anatomic features of the radial collateral artery. A clinical case-control study was performed. The radial collateral artery was studied with color Doppler sonography in 15 healthy volunteers. The origins, courses, variations, and locations of the perforators of the radial collateral artery were recorded. The results and data from the color Doppler sonographic investigation were compared with an anatomic study that was performed on 22 adult cadaveric upper limb specimens. The volunteer group (14 of 15 volunteers) and the cadaveric group (19 of 22 upper arm specimens) clearly showed that the branch pattern of the arterial supply was as follows: brachial artery → deep brachial artery → radial collateral artery → posterior radial collateral artery → myocutaneous perforator. Variations in the origin of the radial collateral artery were identified in 1 volunteer bilaterally and in 3 upper arm specimens. The diameters of the artery and vein measured at the distal insertion of the deltoid and the origin of the deep brachial artery were not significantly different between the volunteer and cadaver groups (P > .05). Due to the difference in measuring methods, the length of the vascular pedicles was significantly different between the groups (P < .05). Color Doppler sonography can facilitate the preoperative assessment of the origin, course, variations, and locations of the radial collateral artery and therefore may increase the success rate of lateral upper arm flap transfer. © 2016 by the American Institute of Ultrasound in Medicine.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

NASA Astrophysics Data System (ADS)

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex.

PubMed

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME.

PubMed

Arenillas, Juan F; Cortijo, Elisa; García-Bermejo, Pablo; Levy, Elad I; Jahan, Reza; Goyal, Mayank; Saver, Jeffrey L; Albers, Gregory W

2017-01-01

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy. Unique identifier: NCT0165746.

48 CFR 32.304-6 - Other collateral security.

Code of Federal Regulations, 2010 CFR

2010-10-01

... GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Loan Guarantees for Defense Production 32.304-6 Other collateral security. The following are examples of other forms of security that, although seldom invoked...

48 CFR 32.304-6 - Other collateral security.

Code of Federal Regulations, 2011 CFR

2011-10-01

... GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Loan Guarantees for Defense Production 32.304-6 Other collateral security. The following are examples of other forms of security that, although seldom invoked...

Revision with suture-tape augmentation after failed collateral ligament reconstruction for chronic interphalangeal instability of the hallux.

PubMed

Cho, Byung-Ki; Park, Ji-Kang; Choi, Seung-Myung; SooHoo, Nelson F

2017-12-01

Chronic varus instability or recurrent subluxation following isolated interphalangeal dislocation of the hallux is a rare injury. No consensus has been reached regarding the best joint-salvage procedure for patients with the failed collateral ligament reconstruction using tendon graft. We report a case who achieved satisfactory clinical outcome through a modified surgical procedure (revision collateral ligament reconstruction augmented with suture-tape). Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Isolated lateral collateral ligament complex injury in rock climbing and Brazilian Jiu-jitsu.

PubMed

Davis, Bryan A; Hiller, Lucas P; Imbesi, Steven G; Chang, Eric Y

2015-08-01

We report two occurrences of high-grade tears of the lateral collateral ligament complex (LCLC), consisting of the anterolateral ligament (ALL) and fibular collateral ligament (FCL). One injury occurred in a rock climber and the other in a martial artist. Increasing awareness of isolated injuries of the LCLC will allow for appropriate diagnosis and management. We review and discuss the anatomy of the LCLC, the unique mechanism of isolated injury, as well as physical and imaging examination findings.

Lone-actor Terrorism and Impulsivity.

PubMed

Meloy, J Reid; Pollard, Jeffrey W

2017-11-01

In some recent cases of lone-actor terrorism, there is evidence the subject acted impulsively, often in response to a triggering event which contained a loss and humiliation. Evidence suggests the subjects acted precipitously, despite planning and preparation carried out in the preceding weeks or months, and their attacks failed to include the often considerable preparation that had been done. The pathway became a runway. The authors recommend the traditional assessment of impulsivity in persons of concern for lone acts of terrorism, as well as other proximal warning behaviors for targeted violence. Both indirect and direct assessment guidelines are proposed, with an emphasis upon self-report, psychological testing, collateral data gathering, and historical records. © 2017 American Academy of Forensic Sciences.

Corkscrew collaterals in atherosclerosis obliterans.

PubMed

Fujii, Yuichi; Ueda, Tomohiro; Uchimura, Yuko; Teragawa, Hiroki

2017-12-01

Marked calcifications in the femoral artery obscured imaging of the artery in computed tomography (CT) and duplex ultrasonography. The presence of corkscrew collateral arteries in patients with Atherosclerosis obliterans (ASO) indicates total artery occlusion.

26 CFR 403.29 - Deposit of collateral.

Code of Federal Regulations, 2011 CFR

2011-04-01

... principal by the United States, may be pledged and deposited by claimants as collateral security in lieu of corporate surety bonds in accordance with the provisions of Treasury Department Circular No. 154, revised...

26 CFR 403.29 - Deposit of collateral.

Code of Federal Regulations, 2012 CFR

2012-04-01

... principal by the United States, may be pledged and deposited by claimants as collateral security in lieu of corporate surety bonds in accordance with the provisions of Treasury Department Circular No. 154, revised...

26 CFR 403.29 - Deposit of collateral.

Code of Federal Regulations, 2010 CFR

2010-04-01

... principal by the United States, may be pledged and deposited by claimants as collateral security in lieu of corporate surety bonds in accordance with the provisions of Treasury Department Circular No. 154, revised...

Embolization of Collateral Vessels Using Mechanically Detachable Coils in Young Children with Congenital Heart Disease

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

Sato, Y.; Ogino, H.; Hara, M.

2003-11-15

Our objective was to evaluate the usefulness of embolizing collateral vessels using mechanically detachable coils (MDCs) in children aged 3 years or younger with congenital heart disease. The subjects were 8 children with congenital heart disease featuring collateral vessels (age 18 days-3 years): 3 with a single ventricle, 2 with the tetralogy of Fallot, 2 with pulmonary atresia, and 1 with a ventricular septal defect. The embolized vessels were the major aortopulmonary collateral artery (MAPCA) in 5 patients, the persistent left superior vena cava in 2, and the coronary arteriovenous fistula in 1. A 4 or a 5 F cathetermore » was used as the guiding device, and embolization was performed using MDCs and other conventional coils introduced through the microcatheter. One patient had growth of new MAPCAs after embolization, and these MAPCAs were also embolized with MDCs. Thus, a total of 9 embolization procedures were performed in 8 patients. Complete occlusion of the collateral vessels was achieved in 8 of 9 procedures (89%). Seven of 8 patients (88%) had uneventful courses after embolization, and MDC procedures appeared to play important roles in avoiding coil migration and achievement of safe coil embolization. One patient who underwent MAPCA embolization showed no improvement in heart function and died 2 months and 19 days later. Embolization of collateral vessels using MDCs in young children with congenital heart disease can be an effective procedure and a valuable adjunct to surgical management.« less

Contrast-Induced Nephropathy Is Less Common in Patients with Good Coronary Collateral Circulation.

PubMed

Avci, Eyup; Yildirim, Tarik; Kadi, Hasan

2017-10-01

Contrast-induced nephropathy (CIN) is a typically reversible type of acute renal failure that develops after exposure to contrast agents; underlying endothelial dysfunction is thought to be an important risk factor for CIN. Although the mechanism of coronary collateral circulation (CCC) is not fully understood, a pivotal role of the endothelium has been reported in many studies. The aim of this study was to investigate whether there is a relationship between CCC and CIN. Patients with at least one occluded major coronary artery and blood creatinine analyses performed before and on the second day after angiography were included in the study. CIN was defined as a 25% or greater elevation of creatinine on the second day after exposure to the contrast agent. Collateral grading was performed according to the Rentrop classification. Patients were grouped according to whether they developed CIN or not, i.e., CIN(-) and CIN(+) group. A total of 214 patients who met the inclusion criteria were included in the study. CIN was diagnosed in 43 patients (20.1%) in the study population. Good CCC was identified in 112 patients (65.5%) in the CIN(-) group, whereas it was identified in 13 patients (30.2%) in the CIN(+) group. In the CIN(-) group, good CCC was significantly more frequent ( p < 0.001). Furthermore, collateral circulation was an independent predictor of CIN. Good collateral circulation was associated with a lower frequency of CIN, and poor collateral circulation was an independent predictor of CIN.

Dynamic Knee Alignment and Collateral Knee Laxity and Its Variations in Normal Humans

PubMed Central

Deep, Kamal; Picard, Frederic; Clarke, Jon V.

2015-01-01

Alignment of normal, arthritic, and replaced human knees is a much debated subject as is the collateral ligamentous laxity. Traditional quantitative values have been challenged. Methods used to measure these are also not without flaws. Authors review the recent literature and a novel method of measurement of these values has been included. This method includes use of computer navigation technique in clinic setting for assessment of the normal or affected knee before the surgery. Computer navigation has been known for achievement of alignment accuracy during knee surgery. Now its use in clinic setting has added to the inventory of measurement methods. Authors dispel the common myth of straight mechanical axis in normal knees and also look at quantification of amount of collateral knee laxity. Based on the scientific studies, it has been shown that the mean alignment is in varus in normal knees. It changes from lying non-weight-bearing position to standing weight-bearing position in both coronal and the sagittal planes. It also varies with gender and race. The collateral laxity is also different for males and females. Further studies are needed to define the ideal alignment and collateral laxity which the surgeon should aim for individual knees. PMID:26636090

Navy Safety Center data on the effects of fire protection systems on electrical equipment

NASA Astrophysics Data System (ADS)

Levine, Robert S.

1991-04-01

Records of the Navy Safety Center, Norfolk, VA were reviewed to find data relevant to inadvertant operation of installed fire extinguishing systems in civilian nuclear power plants. Navy data show the incidence of collateral fire or other damage by fresh water on operating electrical equipment in submarines and in shore facilities is about the same as the civilian experience, about 30 percent. Aboard surface ships, however, the collateral damage incidence in much lower, about 15 percent. With sea water, the collateral damage incidence is at least 75 percent. It is concluded that the fire extinguisher water has to be contaminated, as by rust in sprinkler systems or deposited salt spray, for most collateral damage to occur. Reasons for inadvertant operation (or advertant operation) of firex systems at shore facilities, submarines, and surface ships resemble those for nuclear power plants. Mechanical or electrical failures lead the list, followed by mishaps during maintenance. Detector and alarm system failures are significant problems at Navy shore facilities, and significant at nuclear power plants. Fixed halon and CO2 systems in shore facilities cause no collateral damage. Lists of individual Navy incidents with water and with halon and carbon dioxide are included as appendices.

Repetitive ischemia increases myocardial dimethylarginine dimethylaminohydrolase 1 expression.

PubMed

Zhang, Ping; Fassett, John T; Zhu, Guangshuo; Li, Jingxin; Hu, Xinli; Xu, Xin; Chen, Yingjie; Bache, Robert J

2017-06-01

Pharmacologic inhibition of nitric oxide production inhibits growth of coronary collateral vessels. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme that degrades asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. Here we examined regulation of the ADMA-DDAH1 pathway in a canine model of recurrent myocardial ischemia during the time when coronary collateral growth is known to occur. Under basal conditions, DDAH1 expression was non-uniform across the left ventricular (LV) wall, with expression strongest in the subepicardium. In response to ischemia, DDAH1 expression was up-regulated in the midmyocardium of the ischemic zone, and this was associated with a significant reduction in myocardial interstitial fluid (MIF) ADMA. The decrease in MIF ADMA during ischemia was likely due to increased DDAH1 because myocardial protein arginine N-methyl transferase 1 (PRMT1) and the methylated arginine protein content (the source of ADMA) were unchanged or increased, respectively, at this time. The inflammatory mediators interleukin (IL-1β) and tumor necrosis factor (TNF-α) were also elevated in the midmyocardium where DDAH1 expression was increased. Both of these factors significantly up-regulated DDAH1 expression in cultured human coronary artery endothelial cells. Taken together, these results suggest that inflammatory factors expressed in response to myocardial ischemia contributed to up-regulation of DDAH1, which was responsible for the decrease in MIF ADMA.

Conservative Management of an Epicardial Collateral Perforation During Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention.

PubMed

Ngo, Christian; Christopoulos, George; Brilakis, Emmanouil S

2016-01-01

Coronary artery perforation is a highly feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and can lead to pericardial effusion, tamponade, and, rarely, emergent cardiac surgery. Perforation of epicardial collaterals during retrograde CTO-PCI may be particularly challenging to treat, as embolization from both sides of the perforation may be required to control the bleeding. However, conservative measures can occasionally be effective. We present a case of epicardial collateral vessel perforation that was managed conservatively with anticoagulation reversal.

Open dislocation of the proximal interphalangeal joint of the little finger subsequent to chronic radial collateral ligament injury: a case report of primary ligament reconstruction with a half-slip of the flexor digitorum superficialis: Case Report.

PubMed

Wada, Kazuma; Hibino, Naohito; Kondo, Kenji; Yoshioka, Shinji; Terai, Tomoya; Henmi, Tatsuhiko; Sairyo, Koichi

2015-01-01

Open dislocation of the proximal interphalangeal (PIP) joint is relatively rare. We report a case of a 32-year-old man who had open dislocation of the PIP joint of the little finger while playing American football. He had a history of chronic radial collateral ligament injury. We reconstructed the radial collateral ligament with a half-slip of the flexor digitorum superficialis tendon.

Clinical study of the hypothesis of endogenous collateral wind on acute coronary syndrome: a review.

PubMed

Wang, Xian; Zhang, Cong; Yang, Ran; Zhu, Haiyan; Zhao, Huaibing; Li, Xiaoming

2014-01-01

Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of "endogenous collateral wind" based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine. Through successful coronary angiography (CAG), and intravascular ultrasound (IVUS), patients with coronary artery disease were made the differential diagnosis such as blood stasis, blood stasis due to phlegm obstruction, and endogenous collateral wind. The levels of plasma inflammatory marker were measured to study on the characteristics of "endogenous collateral wind". Luo heng dripping pills with promoting blood circulation to expel wind-evil, and remove wetness were made based on the hypothesis of "endogenous collateral wind" on ACS. Patients with unstable angina were randomly divided into 3, groups based on therapeutic methods: conventional therapy group, Luo Heng dripping pills group and Tongxinluo caps. Differences among groups were compared. There were great changes in number and degree of coronary arteriostenosis confirmed by CAG, the types of ACC/AHA lesion and Levin lesion confirmed by CAG, remodeling index, positive or negative remodeling percentage measured by IVUS, the plasma levels of plasma inflammatory marker measured by ELLSA in the patients with endogenous collateral wind, compared with patients with blood stasis and blood stasis due to phlegm obstruction. The total effective rate of improved angina in Luo Heng dripping pills group was significantly higher than those in other two groups. The levels of plasma inflammatory marker were significantly lower in Luo Heng dripping pills group. There were some pathological basis which were found about the hypothesis of "endogenous collateral wind" on acute coronary syndrome. It provided evidences for patients with coronary artery disease treated by medicines with expelling evil-wind, and removing wetness.

Dynamic Magnetic Resonance Angiography Provides Collateral Circulation and Hemodynamic Information in Acute Ischemic Stroke.

PubMed

Hernández-Pérez, María; Puig, Josep; Blasco, Gerard; Pérez de la Ossa, Natalia; Dorado, Laura; Dávalos, Antoni; Munuera, Josep

2016-02-01

Contrary to usual static vascular imaging techniques, contrast-enhanced dynamic magnetic resonance angiography (dMRA) enables dynamic study of cerebral vessels. We evaluated dMRA ability to assess arterial occlusion, cerebral hemodynamics, and collateral circulation in acute ischemic stroke. Twenty-five acute ischemic stroke patients with proximal anterior circulation occlusion underwent dMRA on a 3T scanner within 12 hours of symptoms onset. Diffusion weighted imaging, Tmax6 s lesion volumes and hypoperfusion intensity ratio as volume of Tmax>6 s/volume of Tmax>10 s were measured. Site and grade of occlusion (Thrombolysis in Myocardial Infarction criteria) were evaluated on time-of-flight MRA and dMRA. Leptomeningeal collaterality (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR] Scale) and asymmetries in venous clearance were assessed exclusively on dMRA. Collateral filling was dichotomized into incomplete (ASITN/SIR 0-2) or complete (ASITN/SIR 3-4). On dMRA, site of occlusion was M1 in 21 patients, tandem internal carotid artery/M1 in 2 and tandem internal carotid artery/terminal internal carotid artery in 2 patients. Three tandem occlusions were not detected on time-of-flight-MRA. All patients had Thrombolysis in Myocardial Infarction 0 to 1 on time-of-flight-MRA, but three of them had Thrombolysis in Myocardial Infarction 2 on dMRA. Complete collateral filling (n=12, 48%) was associated with smaller diffusion weighted imaging lesion volume (P=0.039), smaller hypoperfused volume (P=0.018), and lower hypoperfusion intensity ratio (P=0.006). Patients with symmetrical clearance of transverse sinuses (52%) were more likely to have complete collateral filling (P=0.015). As a fast, direct, feasible, noninvasive, and reliable method to assess site of occlusion, collateral circulation and hemodynamic alterations, dMRA provides profound insights in acute stroke. © 2015 American Heart Association, Inc.

[Internal fixation with one-hole microplate for the treatment of collateral ligament injuries of the metacarpophalangeal joint of the thumb combined with fracture].

PubMed

Wang, Xi-Xun; Sun, De-Tao; Chen, Xu-Hui; Li, Jun; Cui, Yan; Hu, Ji-Chao; Shu, Zheng-Hua; He, Jian; Ding, Chao-Qi; Chen, Bo

2015-03-01

To study clinical effects of one-hole microplate internal fixation for the treatment of collateral ligament injuries of the metacarpophalangeal joint of the thumb combined with fracture. Twenty-two patients (16 males, 6 females) with collateral ligament injuries of the metacarpophalangeal joint of the thumb combined fracture were treated with one-hole microplate internal fixation. The age of the patients ranged from 18 to 53 years old with a mean age of 28.5 years old. The duration from injury to surgery ranged from 2 hours to 2 months, and the mean time was 6 days. All the patients had collateral ligament injuries combined with fracture of the metacarpophalangeal joint of the thumb. Thirteen patients had injuries in the right hand and 9 patients had injuries in the left hand. There were 18 cases of closed wound and 4 cases of open wound. Eighteen patients had fresh injuries (< 2 weeks) and 4 had old injuries (> 2 weeks). Sixteen patients had injuries in the ulnar collateral ligament of the thumb combined with fracture, 6 patients had radial collateral ligament injuries of the thumb combined with fracture, 4 cases of which were complicated with injuries of abductor pollicis brevis and the end of the flexor pollicis brevis tender. The size of the avulsed fragment was about 3.0 mm x 4.0 mm to 6.0 mm x 7.0 mm. The incisions of 22 patients healed by first intention. The follow-up periods ranged from 6 months to 5 years old,with an average of 2.5 years old. The thumb function was evaluated by Saetta and other evaluation criteria, and 20 patients got an excellent result and 2 good. The application of one-hole microplate internal fixation in treating collateral ligament injuries with fracture of the metacarpophalangeal joint of the thumb is an effective method.

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

Rai, Ansaar T., E-mail: ansaar.rai@gmail.com; Jhadhav, Yahodeep; Domico, Jennifer

Purpose: To identify factors impacting outcome in patients undergoing interventions for acute ischemic stroke (AIS). Materials and Methods: This was a retrospective analysis of patients undergoing endovascular therapy for AIS secondary during a 30 month period. Outcome was based on modified Rankin score at 3- to 6-month follow-up. Recanalization was defined as Thrombolysis in myocardial infarction score 2 to 3. Collaterals were graded based on pial circulation from the anterior cerebral artery either from an ipsilateral injection in cases of middle cerebral artery (MCA) occlusion or contralateral injection for internal carotid artery terminus (ICA) occlusion as follows: no collaterals (grademore » 0), some collaterals with retrograde opacification of the distal MCA territory (grade 1), and good collaterals with filling of the proximal MCA (M2) branches or retrograde opacification up to the occlusion site (grade 2). Occlusion site was divided into group 1 (ICA), group 2 (MCA with or without contiguous M2 involvement), and group 3 (isolated M2 or M3 branch occlusion). Results: A total of 89 patients were studied. Median age and National Institutes of health stroke scale (NIHSS) score was 71 and 15 years, respectively. Favorable outcome was seen in 49.4% of patients and mortality in 25.8% of patients. Younger age (P = 0.006), lower baseline NIHSS score (P = 0.001), successful recanalization (P < 0.0001), collateral support (P = 0.0008), distal occlusion (P = 0.001), and shorter procedure duration (P = 0.01) were associated with a favorable outcome. Factors affecting successful recanalization included younger age (P = 0.01), lower baseline NIHSS score (P = 0.05), collateral support (P = 0.01), and shorter procedure duration (P = 0.03). An ICA terminus occlusion (P < 0.0001), lack of collaterals (P = 0.0003), and unsuccessful recanalization (P = 0.005) were significantly associated with mortality. Conclusion: Angiographic findings and preprocedure variables can help prognosticate procedure outcomes in patients undergoing endovascular therapy for AIS.« less

Treatment of posterior cruciate ligament tibial avulsion by a minimally-invasive open posterior approach.

PubMed

Abdallah, Ahmed Abdelbadie; Arafa, Mohammed S

2017-07-01

To assess the surgical technique and report the outcomes following fixation of PCL bony avulsions through mini-invasive posterior knee approach as described by Burks and Schaffer. From June 2012 to July 2015, 27 patients enrolled in the study (21 males and 6 females). Fixation of tibial PCL avulsion fractures was done with one or two cannulated screws, or sutures through Burks and Schaffer's approach. The mean interval before surgery was 16days (1-70) .Patients was followed up for an average of 51 weeks. The outcome measures evaluated at final follow-up were (1) clinical stability as assessed by posterior drawer test, (2) radiologic union, (3) functional assessment by Lysholm score, and (4) gastrocnemius muscle strength as a measure of morbidity. Average operative time was 43min. Improvement of both subjective Lysholm score (mean 93) and objective stability testing by posterior drawer test (returns to normal in 81.1% of patients) at the final follow-up. Good radiographic union at average of 5.6 weeks. No morbidity of the gastrocnemius with few complications. The approach was fast and safe with excellent visualization. It allows surgeons to address other injuries in the same setting. It can be considered as a minimally-invasive open surgery without surgery-related morbidity. It is a reproducible technique that can be done at any trauma centre by surgeons with average experience. The subjective and objective results of the technique are excellent and comparable to the arthroscopic procedures that needs more specific centres with well-trained surgeons. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Comprehension and explanation of meridians and collaterals theory in the background of the spread of western medicine into the East in the Ming and Qing Dynasties].

PubMed

Li, Su-Yun

2010-06-01

In the background of the spread of western medicine into the East in the Ming and Qing Dynasties, Chinese doctors who had accepted western medicine referred to western medical knowledge and began to use the methods of anatomical observation and demonstrating to explain the objective structure of meridians and collaterals. They tried to adopt the artery and vessel explaining the shape of meridian and the blood circle and pulmonary respiration explaining the circulation of Ying-Wei. When the anatomy structures could not perfectly equal to meridians and collaterals, some doctors put forward the gasification feature of meridian to explain the reason. These results suggest that there are difference between meridians and collaterals and pure anatomy concepts, which serves as significant reference and edification for later generations.

Fenestration of axillary vein by a variant axillary artery.

PubMed

Hadimani, S; Desai, S D; Bagoji, I B; Patil, B S

2013-01-01

Variations of venous pattern in the arm are common. In this case report, we present a variation of axillary artery and vein. During routine educational dissections of axillary region, it was observed that a fenestrated axillary vein was perforated by a variant axillary artery in right arm of an old male cadaver. The axillary artery which was fenestrated through axillary vein had only two branches arising from its second part and no branches from its remaining distal parts. The branches are thoraco-acromial (usual) and another large collateral (unusual) branch. This collateral branch is the origin of several important arteries as the subscapular, circumflex scapular, posterior circumflex humeral and lateral thoracic arteries. We propose to name this artery as collateral axillary arterial trunk. The course of this collateral axillary arterial trunk and its branches and also clinical significance of this variation are discussed in the paper.

Impact of time to therapy and presence of collaterals on the efficacy of FX06 in acute ST elevation myocardial infarction: a substudy of the F.I.R.E., the Efficacy of FX06 in the prevention of myocardial reperfusion injury trial.

PubMed

Hallén, Jonas; Petzelbauer, Peter; Schwitter, Jürg; Geudelin, Bernard; Buser, Peter; Atar, Dan

2010-04-01

To determine whether the efficacy of FX06 was dependent upon the timing of reperfusion therapy or the presence of collaterals in the Efficacy of FX06 in the prevention of myocardial reperfusion injury (F.I.R.E.) trial. Two hundred and thirty-four (234) patients presenting with acute ST-segment elevation myocardial infarction were randomised to FX06 or matching placebo given as an intravenous bolus at reperfusion. Infarct size was assessed at 5-7 days and four months after myocardial infarction by cardiac magnetic resonance imaging determined total late enhancement and necrotic core zone. Patients were stratified according to presentation status (time-to-therapy <3 hours, n=108; time-to-therapy=3-6 hours, n=115) and presence of collaterals (yes, 46; no, 177). There were no statistically significant differences between groups at day 5-7. At four months, we observed statistically significant reductions of both measures of infarct size (0.3% vs. 2.4%, p=0.038; 8.0% vs. 16.0%, p=0.032) in the group given FX06 and presenting early. There was also a statistically significant reduction of total late enhancement zone among patients given FX06 with collaterals (7.3% vs. 15.2%, p=0.043). No differences were evident among late presenters or those without collaterals. FX06 significantly reduced infarct size at four months in the early presenters and in those with collaterals.

Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats.

PubMed

Cipolla, Marilyn J; Linfante, Italo; Abuchowski, Abe; Jubin, Ronald; Chan, Siu-Lung

2018-05-01

Similar to patients with chronic hypertension, spontaneously hypertensive rats (SHR) develop fast core progression during middle cerebral artery occlusion (MCAO) resulting in large final infarct volumes. We investigated the effect of Sanguinate™ (SG), a PEGylated carboxyhemoglobin (COHb) gas transfer agent, on changes in collateral and reperfusion cerebral blood flow and brain injury in SHR during 2 h of MCAO. SG (8 mL/kg) or vehicle ( n = 6-8/group) was infused i.v. after 30 or 90 min of ischemia with 2 h reperfusion. Multi-site laser Doppler probes simultaneously measured changes in core MCA and collateral flow during ischemia and reperfusion using a validated method. Brain injury was measured using TTC. Animals were anesthetized with choral hydrate. Collateral flow changed little in vehicle-treated SHR during ischemia (-8 ± 9% vs. prior to infusion) whereas flow increased in SG-treated animals (29 ± 10%; p < 0.05). In addition, SG improved reperfusion regardless of time of treatment; however, brain injury was smaller only with early treatment in SHR vs. vehicle (28.8 ± 3.2% vs. 18.8 ± 2.3%; p < 0.05). Limited collateral flow in SHR during MCAO is consistent with small penumbra and large infarction. The ability to increase collateral flow in SHR with SG suggests that this compound may be useful as an adjunct to endovascular therapy and extend the time window for treatment.

Effects of tibial plateau angle and spacer thickness applied during in vitro canine total knee replacement on three-dimensional kinematics and collateral ligament strain.

PubMed

Baker, Katherine M; Foutz, Timothy L; Johnsen, Kyle J; Budsberg, Steven C

2014-09-01

To quantify the 3-D kinematics and collateral ligament strain of stifle joints in cadaveric canine limbs before and after cranial cruciate ligament transection followed by total knee replacement (TKR) involving various tibial plateau angles and spacer thicknesses. 6 hemi-pelvises collected from clinically normal nonchondrodystrophic dogs (weight range, 25 to 35 kg). Hemi-pelvises were mounted on a modified Oxford knee rig that allowed 6 degrees of freedom of the stifle joint but prevented mechanical movement of the hip and tarsal joints. Kinematics and collateral ligament strain were measured continuously while stifle joints were flexed. Data were again collected after cranial cruciate ligament transection and TKR with combinations of 3 plateau angles (0°, 4°, and 8°) and spacer thicknesses (5, 7, and 9 mm). Presurgical (ie, normal) stifle joint rotations were comparable to those previously documented for live dogs. After TKR, kinematics recorded for the 8°, 5-mm implant most closely resembled those of unaltered stifle joints. Decreasing the plateau angle and increasing spacer thickness altered stifle joint adduction, internal rotation, and medial translation. Medial collateral ligament strain was minimal in unaltered stifle joints and was unaffected by TKR. Lateral collateral ligament strain decreased with steeper plateau angles but returned to a presurgical level at the flattest plateau angle. Among the constructs tested, greatest normalization of canine stifle joint kinematics in vitro was achieved with the steepest plateau angle paired with the thinnest spacer. Furthermore, results indicated that strain to the collateral ligaments was not negatively affected by TKR.

Microsurgical Repair of Ruptured Aneurysms Associated with Moyamoya-Pattern Collateral Vessels of the Middle Cerebral Artery: A Report of Two Cases.

PubMed

Lang, Min; Moore, Nina Z; Witek, Alex M; Kshettry, Varun R; Bain, Mark D

2017-09-01

Patients with Moyamoya or other intracranial steno-occlusive disease are at risk for developing aneurysms associated with flow through collateral vessels. Because these lesions are rare, the optimal management remains unclear. Here, we describe 2 cases of microsurgical repair of ruptured collateral vessel aneurysms associated with middle cerebral artery (MCA) occlusion. The first patient was a 61-year-old man who presented with right frontal and intraventricular hemorrhage. Angiography revealed chronic right M1 occlusion and a 3-mm spherical lenticulostriate aneurysm. The frontal lobe hematoma was evacuated to reveal the aneurysm, which was safely cauterized and resected by coagulating and dividing the lenticulostriate parent vessel. The procedure was carried out with neuronavigation guidance and intraoperative neuromonitoring. The patient was discharged with no neurologic deficits. The second patient was a 53-year-old woman who presented with subarachnoid and intracerebral hemorrhage. Computed tomography angiogram showed a 2-mm saccular MCA aneurysm. Emergency left decompressive hemicraniectomy and hematoma evacuation were performed. The aneurysm, arising from a small collateral type vessel, was safely clipped without complications. Postoperative angiography revealed absence of the superior MCA trunk with a dense network of collateral vessels at the site of the clipped aneurysm. The patient recovered well and was ambulating independently 6 months postoperatively. No rebleeding occurred in the 2 patients. Our experience suggests that patients with MCA occlusion can harbor associated aneurysms related to flow through collateral vessels and can present with hemorrhage. Microsurgical repair of these aneurysms can be performed safely to prevent rebleeding. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of VEGF and KDR Polymorphisms in Moyamoya Disease and Collateral Revascularization

PubMed Central

Park, Young Seok; Jeon, Young Joo; Kim, Hyun Seok; Chae, Kyu Young; Oh, Seung-Hun; Han, In Bo; Kim, Hyun Sook; Kim, Won-Chan; Kim, Ok-Joon; Kim, Tae Gon; Choi, Joong-Uhn; Kim, Dong-Seok; Kim, Nam Keun

2012-01-01

We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF −2578, −1154, −634, and 936) and kinase insert domain containing receptor (KDR −604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (−2578, −1154, −634, and 936) and KDR (−604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF −2578, −1154, −634, and 936 or KDR −604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the −634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR −604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF −634 had better collateral vessel formation after surgery. Our results suggest that the VEGF −634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation. PMID:23077562

28 CFR 104.47 - Collateral sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... determining the appropriate collateral source offset for future benefit payments, the Special Master may employ an appropriate methodology for determining the present value of such future benefits. In... compensation, including life insurance, pension funds, death benefits programs, and payments by Federal, State...

12 CFR 614.4266 - Personal and intangible property evaluations.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 614.4266 Section 614.4266 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS Collateral Evaluation Requirements § 614.4266 Personal and intangible property... shall include provisions for periodic collateral inspections and verification by the institution's...

MR imaging of the elbow in the injured athlete.

PubMed

Wenzke, Daniel R

2013-03-01

This article summarizes key MR imaging findings in common athletic elbow injuries including little leaguer's elbow, Panner disease, osteochondritis dissecans, olecranon stress fracture, occult fracture, degenerative osteophyte formation, flexor-pronator strain, ulnar collateral ligament tear, lateral ulnar collateral ligament and radial collateral ligament tear, lateral epicondylitis, medial epicondylitis, biceps tear, bicipitoradial bursitis, triceps tear, olecranon bursitis, ulnar neuropathy, posterior interosseous nerve syndrome, and radial tunnel syndrome. The article also summarizes important technical considerations in elbow MR imaging that enhance image quality and contribute to the radiologist's success. Copyright © 2013 Elsevier Inc. All rights reserved.

The Dual Role of Cerebral Autoregulation and Collateral Flow in the Circle of Willis After Major Vessel Occlusion.

PubMed

Kennedy McConnell, Flora; Payne, Stephen

2017-08-01

Ischaemic stroke is a leading cause of death and disability. Autoregulation and collateral blood flow through the circle of Willis both play a role in preventing tissue infarction. To investigate the interaction of these mechanisms a one-dimensional steady-state model of the cerebral arterial network was created. Structural variants of the circle of Willis that present particular risk of stroke were recreated by using a network model coupled with: 1) a steady-state physiological model of cerebral autoregulation; and 2) one wherein the cerebral vascular bed was modeled as a passive resistance. Simulations were performed in various conditions of internal carotid and vertebral artery occlusion. Collateral flow alone is unable to ensure adequate blood flow ([Formula: see text] normal flow) to the cerebral arteries in several common variants during internal carotid artery occlusion. However, compared to a passive model, cerebral autoregulation is better able to exploit available collateral flow and maintain flows within [Formula: see text] of baseline. This is true for nearly all configurations. Hence, autoregulation is a crucial facilitator of collateral flow through the circle of Willis. Impairment of this response during ischemia will severely impact cerebral blood flows and tissue survival, and hence, autoregulation should be monitored in this situation.

A case of reocclusion of the renal artery diagnosed by the color Doppler method with evaluation of blood flow direction in the collateral circulation of the kidney in addition to the non-detectable blood signal in the renal artery.

PubMed

Hirano, Megumi; Ohta, Tomoyuki; Nakata, Norio; Kawakami, Reina; Takamura, Kimihiro; Matsuda, Tosiharu; Nishioka, Makiko; Sakurai, Tomoo; Matsuo, Kouichi; Miyamoto, Yukio

2014-10-01

A 23-year-old woman was referred to our hospital for an interventional procedure for chronic total occlusion of the right renal artery, probably due to fibromuscular dysplasia (FMD), and for control of renal vascular hypertension. Before percutaneous transluminal renal angioplasty (PTRA), aortography revealed collateral circulation to the right kidney from the lower lumbar artery. After PTRA, however, blood flow in the renal side of the collateral circulation flowed outside from the right renal parenchyma. 4 months later, we could not find a blood flow signal in the right renal artery, and there was a contrary flow signal in the right kidney parenchyma continuously from the extrahilar vessel, possibly a collateral artery. These findings indicated reocclusion of the right artery. We confirmed reocclusion of the renal artery and collateral feeding by contrast dynamic computed tomography (CT), and PTRA was performed again without any complications or reocclusion for 5 months. This is the first case report showing that a back-flowing signal in the right renal parenchyma from the extrahilar artery is useful as an indirect finding suggesting reocclusion.

Medial collateral ligament injuries and subsequent load on the anterior cruciate ligament: a biomechanical evaluation in a cadaveric model.

PubMed

Battaglia, Michael J; Lenhoff, Mark W; Ehteshami, John R; Lyman, Stephen; Provencher, Matthew T; Wickiewicz, Thomas L; Warren, Russell F

2009-02-01

Numerous studies have documented the effect of complete medial collateral ligament injury on anterior cruciate ligament loads; few have addressed how partial medial collateral ligament disruption affects knee kinematics. To determine knee kinematics and subsequent change in anterior cruciate ligament load in a partial and complete medial collateral ligament injury model. Controlled laboratory study. Ten human cadaveric knees were sequentially tested by a robot with the medial collateral ligament intact, in a partial injury model, and in a complete injury model with a universal force-moment sensor measuring system. Tibial translation, rotation, and anterior cruciate ligament load were measured under 3 conditions: anterior load (125 N), valgus load (10 N x m), and internal-external rotation torque (4 N x m; all at 0 degrees and 30 degrees of flexion). Anterior and posterior translation did not statistically increase with a partial or complete medial collateral ligament injury at 0 degrees and 30 degrees of flexion. In response to a 125 N anterior load, at 0 degrees , the anterior cruciate ligament load increased 8.7% (from 99.5 to 108.2 N; P = .006) in the partial injury and 18.3% (117.7 N; P < .001) in the complete injury; at 30 degrees , anterior cruciate ligament load was increased 12.3% (from 101.7 to 114.2 N; P = .001) in the partial injury and 20.6% (122.7 N; P < .001) in the complete injury. In response to valgus torque (10 N x m) at 30 degrees , anterior cruciate ligament load was increased 55.3% (30.4 to 47.2 N; P = .044) in the partial injury model and 185% (86.8 N; P = .001) in the complete injury model. In response to internal rotation torque (4 N.m) at 30 degrees , anterior cruciate ligament load was increased 29.3% (27.6 to 35.7 N; P = .001) in the partial injury model and 65.2% (45.6 N; P < .001) in the complete injury model. The amount of internal rotation at 30 degrees of flexion was significantly increased in the complete injury model (22.8 degrees ) versus the intact state (19.5 degrees ; P < .001). Partial and complete medial collateral ligament tears significantly increased the load on the anterior cruciate ligament. In a partial tear, the resultant load on the anterior cruciate ligament was increased at 30 degrees of flexion and with valgus load and internal rotation torque. Patients may need to be protected from valgus and internal rotation forces after anterior cruciate ligament reconstruction in the setting of a concomitant partial medial collateral ligament tear. This information may help clinicians understand the importance of partial injuries of the medial collateral ligament with a combined anterior cruciate ligament injury complex.

78 FR 14013 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Wheelchair Elevator

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

...: General Requirements for Safety-- Collateral Standard: Electromagnetic Compatibility--Requirements and... electromagnetic compatibility and electrical safety. Firms are now exempt from 510(k) requirements for vertical... Equipment--Part 1-2: General Requirements for Safety--Collateral Standard: Electromagnetic Compatibility...

75 FR 66805 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... from using its customers' securities as collateral to finance its own trading, speculating, or...-dealer is prohibited from commingling the securities of different customers as collateral for a loan without the consent of each customer; second, that a broker-dealer cannot commingle customers' securities...

Targeted Infrared Photoimmunotherapy for Cancer | Center for Cancer Research

Cancer.gov

A longstanding goal of cancer therapy is the extensive destruction of cancer cells with minimal collateral damage to normal cells. This goal has been very hard to accomplish. Most existing efficacious treatments inevitably inflict collateral damage on nearby normal cells and tissue.

7 CFR 1980.331 - Collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Collateral. 1980.331 Section 1980.331 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... security interest is obtained, maintained in existence, and of record to protect the interests of the...

Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy.

PubMed

Jiang, Beisi; Churilov, Leonid; Kanesan, Lasheta; Dowling, Richard; Mitchell, Peter; Dong, Qiang; Davis, Stephen; Yan, Bernard

2017-05-01

Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) ( p =0.001), by 73.9% in diastolic BP (DBP) ( p <0.001) and by 68.5% in mean BP (MBP) ( p <0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP ( p =0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship ( p >0.05). In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.

Intrinsic development of choroidal and thalamic collaterals in hemorrhagic-onset moyamoya disease: case-control study of the Japan Adult Moyamoya Trial.

PubMed

Fujimura, Miki; Funaki, Takeshi; Houkin, Kiyohiro; Takahashi, Jun C; Kuroda, Satoshi; Tomata, Yasutake; Tominaga, Teiji; Miyamoto, Susumu

2018-05-04

OBJECTIVE This study was performed to identify the angiographic features of hemorrhagic-onset moyamoya disease (MMD) in comparison with those of patients with ischemic-onset MMD. METHODS This case-control study compared the data set of the Japan Adult Moyamoya (JAM) Trial with the angiographic data of adult patients with ischemic-onset MMD. The authors analyzed angiograms obtained at onset, classifying the collaterals into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. They then compared the extent of these collaterals, as indicated by the collateral development grade from 0 to 2 in each subtype, between the JAM Trial group and the ischemic-onset group. They also compared the involvement of the posterior cerebral artery (PCA) and Suzuki's angiographic staging between each group. RESULTS Among 89 ischemic-onset patients, 103 symptomatic hemispheres in 80 patients were analyzed and compared with 75 hemorrhagic hemispheres from the JAM Trial. The hemorrhagic-onset patients showed a significantly higher proportion of thalamic anastomosis (p = 0.043) and choroidal anastomosis (< 0.001), as indicated by grade 2 in each subtype, compared with ischemic-onset patients. Suzuki's angiographic staging was significantly higher in the hemorrhagic group (< 0.038). There was no difference in the extent of lenticulostriate anastomosis and PCA involvement between the groups. CONCLUSIONS In adult MMD, the characteristic pattern of the abnormal vascular networks at the base of the brain is different between each onset type. In light of the more prominent development of thalamic and choroidal anastomosis in the JAM Trial group in the present study, development of these collaterals, especially the choroidal collateral extending beyond the lateral ventricle, may play a critical role in hemorrhagic presentation in MMD. Clinical trial registration no. C000000166 ( http://www.umin.ac.jp/ctr/index.htm ).

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

Effect of dehydration on the development of collaterals in acute middle cerebral artery occlusion.

PubMed

Chang, S-W; Huang, Y-C; Lin, L-C; Yang, J-T; Weng, H-H; Tsai, Y-H; Lee, T-H

2016-03-01

Recent large series studies have demonstrated that dehydration is common amongst stroke subjects and is associated with poor outcome. However, the effects of hydration status on the development of collaterals have never been discussed. In this study, the hypothesis that hydration status is an important factor for developing collaterals after acute middle cerebral artery (MCA) infarction was tested. Eighty-seven patients with acute infarction due to occlusion of the MCA were enrolled. Two collateral markers, posterior cerebral artery (PCA) laterality and fluid-attenuated inversion recovery hyperintense vessels (HVs) were assessed from magnetic resonance imaging. Dehydration status was defined by a nitrogen to creatinine ratio ≧ of 15. The associations between dehydration status and the development of collaterals were estimated. Sixty-one of 87 patients (70.1%) were identified as dehydrated. The development of PCA laterality and HVs shows a significant difference between dehydrated and euhydrated patients. A serum nitrogen to creatinine ratio <15, diastolic blood pressure and the presence of a dense MCA on computed tomography were significantly associated with the development of PCA laterality. A serum nitrogen to creatinine ratio <15, the initial National Institutes of Health Stroke Scale score, the presence of a dense MCA and calcifications of the internal carotid artery on computed tomography were significantly associated with the development of HVs. Dehydration remained an independent negative predictor for the development of PCA laterality and HVs in the multivariate analysis. Hydration status is associated with the development of collateral flow after acute MCA occlusion. This preliminary study provides an imaging clue that hydration status and early hydration therapy could be important for acute stroke management. © 2016 EAN.

2'-Hydroxyflavanone ameliorates mesenteric angiogenesis and portal-systemic collaterals in rats with liver fibrosis.

PubMed

Hsin, I-Fang; Lee, Jing-Yi; Huo, Teh-Ia; Lee, Fa-Yauh; Huang, Hui-Chun; Hsu, Shao-Jung; Wang, Sun-Sang; Ho, Hsin-Ling; Lin, Han-Chieh; Lee, Shou-Dong

2016-05-01

Portal-systemic collaterals lead to dreadful consequences in patients with cirrhosis. Angiogenesis participates in the development of liver fibrosis, hyperdynamic circulation, and portal-systemic collaterals. 2'-Hydroxyflavanone (2'-HF), one of the citrus fruits flavonoids, is known to have antiangiogenesis effect without adverse response. However, the relevant effects in liver fibrosis have not been surveyed. Male Wistar rats received thioacetamide (TAA, 100 mg/kg tiw, i.p.) for 6 weeks to induce liver fibrosis. On the 29th to 42nd day, rats randomly received 2'-HF (100 mg/kg, qod, i.p.) or vehicle (corn oil). On the 43rd day, after hemodynamic measurements, the followings were surveyed: (i) severity of collaterals; (ii) mesenteric angiogenesis; (iii) mesenteric proangiogenic factors protein expressions; (iv) Mesenteric vascular endothelial cells apoptosis; and (v) Mesenteric expressions of proteins regulating apoptosis. Compared with the vehicle group, 2'-HF did not significantly change body weight, mean arterial pressure, heart rate, and portal pressure in TAA rats. 2'-HF significantly alleviated the severity of collaterals, but the mesenteric phospho-ERK, ERK, phospho-Akt, Akt, COX1, COX2, VEGF, and VEGFR-2 protein expressions were not altered. The apoptotic index of 2'-HF group was significantly higher and the mesenteric protein expressions of pro-apoptotic factors, NFkB 50, NFkB 65, Bax, phospho-p53, 17 kD cleaved caspase 3, and 17 kD casepase 3 were up-regulated. 2'-HF does not influence the hemodynamics but alleviated the severity of collaterals in rats with liver fibrosis and early portal hypertension. This is, at least partly, attributed to enhanced apoptosis of mesenteric vascular endothelial cells. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Collaterals management during pancreatoduodenectomy in patients with celiac axis stenosis: A systematic review of the literature.

PubMed

Giovanardi, Francesco; Lai, Quirino; Garofalo, Manuela; Arroyo Murillo, Gabriela A; Choppin de Janvry, Eleonore; Hassan, Redan; Larghi Laureiro, Zoe; Consolo, Adriano; Melandro, Fabio; Berloco, Pasquale B

2018-05-15

Celiac axis stenosis (CAS) represents an uncommon and typically innocuous condition. However, when a pancreatic resection is required, a high risk for upper abdominal organs ischemia is observed. In presence of collaterals, such a risk is minimized if their preservation is realized. The aim of the present study is to systematically review the literature with the intent to address the routine management of collateral arteries in the case of CAS patients requiring pancreatoduodenectomy. A systematic search was done in accordance with the PRISMA guidelines, using "celiac axis stenosis" AND "pancreatoduodenectomy" as MeSH terms. Seventy-four articles were initially screened: eventually, 30 articles were identified (n = 87). The main cause of CAS was median arcuate ligament (MAL) (n = 31; 35.6%), followed by atherosclerosis (n = 20; 23.0%). CAS was occasionally discovered during the Whipple procedure in 15 (17.2%) cases. Typically, MAL was divided during surgery (n = 24/31; 77.4%). In the great majority of cases (n = 83; 95.4%), vascular abnormalities involved the pancreatoduodenal arteries (i.e., dilatation, arcade, channels, aneurysms). Collateral arteries were typically preserved, being divided or reconstructed in only 14 (16.1%) cases, respectively. Severe ischemic complications were reported in six (6.9%) patients, 20.0% of whom were reported in patients with preoperatively unknown CAS (p-value 0.06). A correct pre-operative evaluation of anatomical conditions as well as a correct surgical planning represent the paramount targets in CAS patients with arterial collaterals. Vascular flow must be always safeguarded preserving/reconstructing the collaterals or resolving the CAS, with the final intent to avoid dreadful intra- and post-operative complications. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Relative cerebral blood volume as a marker of durable tissue-at-risk viability in hyperacute ischemic stroke.

PubMed

Cortijo, Elisa; Calleja, Ana Isabel; García-Bermejo, Pablo; Mulero, Patricia; Pérez-Fernández, Santiago; Reyes, Javier; Muñoz, Ma Fe; Martínez-Galdámez, Mario; Arenillas, Juan Francisco

2014-01-01

Selection of best responders to reperfusion therapies could be aided by predicting the duration of tissue-at-risk viability, which may be dependant on collateral circulation status. We aimed to identify the best predictor of good collateral circulation among perfusion computed tomography (PCT) parameters in middle cerebral artery (MCA) ischemic stroke and to analyze how early MCA response to intravenous thrombolysis and PCT-derived markers of good collaterals interact to determine stroke outcome. We prospectively studied patients with acute MCA ischemic stroke treated with intravenous thrombolysis who underwent PCT before treatment showing a target mismatch profile. Collateral status was assessed using a PCT source image-based score. PCT maps were quantitatively analyzed. Cerebral blood volume (CBV), cerebral blood flow, and Tmax were calculated within the hypoperfused volume and in the equivalent region of unaffected hemisphere. Occluded MCAs were monitored by transcranial Duplex to assess early recanalization. Main outcome variables were brain hypodensity volume and modified Rankin scale score at day 90. One hundred patients with MCA ischemic stroke imaged by PCT received intravenous thrombolysis, and 68 met all inclusion criteria. A relative CBV (rCBV) >0.93 emerged as the only predictor of good collaterals (odds ratio, 12.6; 95% confidence interval, 2.9-55.9; P=0.001). Early MCA recanalization was associated with better long-term outcome and lower infarct volume in patients with rCBV<0.93, but not in patients with high rCBV. None of the patients with rCBV<0.93 achieved good outcome in absence of early recanalization. High rCBV was the strongest marker of good collaterals and may characterize durable tissue-at-risk viability in hyperacute MCA ischemic stroke.

Accuracy of low-field magnetic resonance imaging versus radiography for guiding injection of equine distal interphalangeal joint collateral ligaments.

PubMed

Lamb, Megan M; Barrett, Jennifer G; White, Nathaniel A; Werre, Stephen R

2014-01-01

Desmopathy of the distal interphalangeal joint collateral ligament is a common cause of lameness in the horse and carries a variable prognosis for soundness. Intralesional treatment has been proposed for improving outcome; however, limited reports describe methods for injecting this ligament. The purpose of this study was to compare accuracy of low-field magnetic resonance imaging (MRI) vs. radiography for injecting the collateral ligament of the distal interphalangeal joint. Equine cadaver digit pairs (n = 10) were divided by random assignment to injection of the ligament by either technique. An observer unaware of injection technique determined injection success based on postinjection MRI and/or gross sections acquired from the proximal, middle, and distal portions of the ligament. McNemar's test was performed to determine statistical difference between injection techniques, the number of injection attempts, and injection of the medial or lateral collateral ligament. Magnetic resonance imaging guided injection was successful more frequently than radiographic-guided injection based on postinjection MRI (24 of 30 vs. 9 of 30; P = 0.0006) and gross sections (26 of 30 vs. 13 of 30; P = 0.0008). At each level of the ligament (proximal, middle, and distal), MRI-guided injection resulted in more successful injections than radiographic guidance. Statistical significance occurred at the proximal aspect of the collateral ligament based on postinjection MRI (P = 0.0143) and the middle portion of the ligament based on gross sections (P = 0.0253). Findings supported future testing of standing, low-field MRI as a technique for delivering intralesional regenerative therapy in live horses with desmopathy of these collateral ligaments. © 2013 American College of Veterinary Radiology.

12 CFR 614.4240 - Collateral definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

....4240 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS... income and/or other collateral, absent the real estate, and the decision to extend credit was, in fact... staff evaluator from another Farm Credit System institution only if the employing institution is not...

12 CFR 614.4240 - Collateral definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

....4240 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS... income and/or other collateral, absent the real estate, and the decision to extend credit was, in fact... staff evaluator from another Farm Credit System institution only if the employing institution is not...

12 CFR 614.4240 - Collateral definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

....4240 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS... income and/or other collateral, absent the real estate, and the decision to extend credit was, in fact... staff evaluator from another Farm Credit System institution only if the employing institution is not...

31 CFR 202.6 - Collateral security.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Collateral security. 202.6 Section 202.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS OF THE FEDERAL...

13 CFR 120.934 - Collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Collateral. 120.934 Section 120.934 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company... must be insured against such hazards and risks as SBA may require, with provisions for notice to SBA...

12 CFR 747.17 - Collateral attacks on adjudicatory proceeding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Collateral attacks on adjudicatory proceeding. 747.17 Section 747.17 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING... adjudicatory proceeding, the challenged adjudicatory proceeding shall continue without regard to the pendency...

12 CFR 614.4240 - Collateral definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

....4240 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS... income and/or other collateral, absent the real estate, and the decision to extend credit was, in fact... staff evaluator from another Farm Credit System institution only if the employing institution is not...

46 CFR 308.509 - Collateral deposit fund.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.509 Collateral deposit fund. (a..., Department of Transportation” for the amount of the fund, or United States Government bonds having a par...

46 CFR 308.509 - Collateral deposit fund.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Open Policy War Risk Cargo Insurance § 308.509 Collateral deposit fund. (a..., Department of Transportation” for the amount of the fund, or United States Government bonds having a par...

46 CFR 308.509 - Collateral deposit fund.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.509 Collateral deposit fund. (a..., Department of Transportation” for the amount of the fund, or United States Government bonds having a par...

46 CFR 308.509 - Collateral deposit fund.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.509 Collateral deposit fund. (a..., Department of Transportation” for the amount of the fund, or United States Government bonds having a par...

46 CFR 308.509 - Collateral deposit fund.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.509 Collateral deposit fund. (a..., Department of Transportation” for the amount of the fund, or United States Government bonds having a par...

12 CFR 614.4255 - Independence requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... collateral supporting a loan shall subsequently participate in any decision related to the loan purchase. ... approve a loan decision on which such person performed a collateral evaluation; or (3) As a director... required to make a credit decision. (b) Officers and employees. If the institution's internal control...

The Effects of a Functional Elbow Brace on Medial Joint Stability: A Case Study

PubMed Central

Pincivero, Danny M.; Rijke, Arie M.; Heinrichs, Kristinn; Perrin, David H.

1994-01-01

Medical elbow ligament sprains in athletics can be traumatic and disabling. In this case report, we outline the effect of a prototype functional elbow brace on joint stability in a female collegiate javelin thrower with an ulnar collateral ligament sprain. A valgus force to both elbows was applied using graded stress radiography (Telos GA-II/E stress device) at 0, 5, 10, and 15 kiloPascals (kPa) of pressure. The increase in gap width between the coronoid process and the medial epicondyle was measured from anteroposterior radiographs to determine medial displacement. The brace resulted in less displacement in both injured and noninjured ulnar collateral ligament; injured ulnar collateral ligament demonstrated greater displacement regardless of condition. The brace restored medial stability to the elbow joint by 49%, 38%, and 35% at 5, 10, and 15 kPa of pressure, respectively. The application of the brace may be useful in athletes with ulnar collateral ligament injuries. ImagesFig 1Fig 2 PMID:16558285

Optimal management of ulnar collateral ligament injury in baseball pitchers

PubMed Central

Hibberd, Elizabeth E; Brown, J Rodney; Hoffer, Joseph T

2015-01-01

The ulnar collateral ligament stabilizes the elbow joint from valgus stress associated with the throwing motion. During baseball pitching, this ligament is subjected to tremendous stress and injury if the force on the ulnar collateral ligament during pitching exceeds the physiological limits of the ligament. Injuries to the throwing elbow in baseball pitchers result in significant time loss and typically surgical intervention. The purpose of this paper is to provide a review of current information to sports medicine clinicians on injury epidemiology, injury mechanics, injury risk factors, injury prevention, surgical interventions, nonsurgical interventions, rehabilitation, and return to play outcomes in baseball pitchers of all levels. PMID:26635490

11 CFR 9033.11 - Documentation of disbursements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... to a payee, the candidate shall present a canceled check negotiated by the payee and either: (i) A... present collateral evidence to document the qualified campaign expense. Such collateral evidence may...) For all other disbursements, the candidate shall present: (i) A record disclosing the full name and...

75 FR 32943 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... basic safety and essential performance--Collateral standard: Electromagnetic compatibility--Requirements... standard: Electromagnetic compatibility--Requirements and tests 5-34 5-53 IEC 60601-1-2 Third edition 2007... for basic safety and essential performance--Collateral standard: Electromagnetic compatibility...

7 CFR 1427.12 - Liens.

Code of Federal Regulations, 2010 CFR

2010-01-01

... tendered as collateral for a loan, even though the liens or encumbrances are satisfied from the loan... less than $50,000. (b) CCC may elect to accept cotton as loan collateral that has warehouse receiving... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Nonrecourse Cotton Loan and Loan Deficiency Payments...

7 CFR 1779.83 - Protective advances.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... Protective advances can only be added to the loan account for purposes of requirements to preserve the value..., but are not limited to, advances made for taxes, annual assessments, ground rent, hazard and flood... associated with the value of the collateral being preserved. (b) Preserving collateral. When considering...

7 CFR 1779.83 - Protective advances.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... Protective advances can only be added to the loan account for purposes of requirements to preserve the value..., but are not limited to, advances made for taxes, annual assessments, ground rent, hazard and flood... associated with the value of the collateral being preserved. (b) Preserving collateral. When considering...

7 CFR 1779.83 - Protective advances.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... Protective advances can only be added to the loan account for purposes of requirements to preserve the value..., but are not limited to, advances made for taxes, annual assessments, ground rent, hazard and flood... associated with the value of the collateral being preserved. (b) Preserving collateral. When considering...

7 CFR 1779.83 - Protective advances.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... Protective advances can only be added to the loan account for purposes of requirements to preserve the value..., but are not limited to, advances made for taxes, annual assessments, ground rent, hazard and flood... associated with the value of the collateral being preserved. (b) Preserving collateral. When considering...

7 CFR 1779.83 - Protective advances.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... Protective advances can only be added to the loan account for purposes of requirements to preserve the value..., but are not limited to, advances made for taxes, annual assessments, ground rent, hazard and flood... associated with the value of the collateral being preserved. (b) Preserving collateral. When considering...

10 CFR 611.111 - Default, demand, payment, and collateral liquidation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Default, demand, payment, and collateral liquidation. 611.111 Section 611.111 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM Direct Loan Program § 611.111 Default, demand, payment, and...

Low prevalence of collateral cerebral circulation in the circle of Willis in patients with severe carotid artery stenosis and recent ischemic stroke.

PubMed

Badacz, Rafał; Przewłocki, Tadeusz; Karch, Izabela; Pieniążek, Piotr; Rosławiecka, Agnieszka; Mleczko, Szymon; Brzychczy, Andrzej; Trystuła, Mariusz; Żmudka, Krzysztof; Kabłak-Ziembicka, Anna

2015-01-01

The circle of Willis is thought to play a key role in development of collateral flow in patients with internal carotid artery stenosis (ICAS). To assess flow in the circle of Willis in patients with recent ischemic stroke (IS). The study included 371 patients, 102 symptomatic with severe ICAS and recent IS (within the last 3 months) (group I) and 269 asymptomatic with severe ICAS (group II). Flow in the middle (MCA), anterior (ACA) and posterior (PCA) cerebral arteries and pattern of the cross-flow through anterior (ACoA) and posterior (PCoA) communicating arteries were assessed with transcranial color-coded Doppler ultrasonography (TCCD). The ACoA or PCoA was less prevalent in group I than in group II (54% vs. 78%, p < 0.001 and 20% vs. 42%, p < 0.001, respectively), resulting in lower peak-systolic velocity (PSV) in the MCA in group I vs. group II (p = 0.015). Any collateral pathway was present in 67% of patients in group I, compared to 86% in group II (p < 0.001). Both PSV and end-diastolic (EDV) flow velocity in the ACA were lower in patients with recent IS, compared to asymptomatic subjects (71 ±24 cm/s vs. 86 ±34 cm/s, p < 0.001 and 32 ±12 cm/s vs. 37 ±17 cm/s, p = 0.038, respectively). Presence of ACoA or PCoA and higher PSV in the MCA and ACA were associated with significant risk reduction of IS (RR = 0.28 (95% CI = 0.16-0.49, p < 0.001), RR = 0.28 (95% CI = 0.15-0.52, p < 0.001), RR = 0.97 (95% CI = 0.96-0.99, p < 0.001), RR = 0.99 (95% CI = 0.98-0.99, p < 0.032), respectively). However, ROC curves failed to show reliable MCA or ACA PSV cut-offs for IS risk assessment. The ACoA and PCoA seem to play a key role in the evaluation of IS risk in subjects with severe ICAS.

Collateral non cardiac findings in clinical routine CT coronary angiography: results from a multi-center registry.

PubMed

La Grutta, Ludovico; Malagò, Roberto; Maffei, Erica; Barbiani, Camilla; Pezzato, Andrea; Martini, Chiara; Arcadi, Teresa; Clemente, Alberto; Mollet, Nico R; Zuccarelli, Alessandra; Krestin, Gabriel P; Lagalla, Roberto; Pozzi Mucelli, Roberto; Cademartiri, Filippo; Midiri, Massimo

2015-12-01

The aim of the study was to evaluate the prevalence of collateral findings detected in computed tomography coronary angiography (CTCA) in a multi-center registry. We performed a retrospective review of 4303 patients (2719 males, mean age 60.3 ± 10.2 years) undergoing 64-slice CTCA for suspected or known coronary artery disease (CAD) at various academic institutions between 01/2006 and 09/2010. Collateral findings were recorded and scored as: non-significant (no signs of relevant pathology, not necessary to be reported), significant (clear signs of pathology, mandatory to be reported), or major (remarkable pathology, mandatory to be reported and further investigated). We detected 6886 non-cardiac findings (1.6 non cardiac finding per patient). Considering all centers, only 865/4303 (20.1 %) patients were completely without any additional finding. Overall, 2095 (30.4 %) non-significant, 4486 (65.2 %) significant, and 305 (4.4 %) major findings were detected. Among major findings, primary lung cancer was reported in 21 cases. In every center, most prevalent significant findings were mediastinal lymph nodes >1 cm. In 256 patients, collateral findings were clinically more relevant than coexisting CAD and justified the symptoms of patients. The prevalence of significant and major collateral findings in CTCA is high. Radiologists should carefully evaluate the entire scan volume in each patient.

Small vessel hematocrit in ischemic myocardium

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

Gumm, D.C.; Cooper, S.M.; Marcus, M.L.

1986-03-01

As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement ofmore » retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.« less

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

Evaluation of the anterior chamber angle in Asian Indian eyes by ultrasound biomicroscopy and gonioscopy.

PubMed

Kaushik, Sushmita; Jain, Rajeev; Pandav, Surinder Singh; Gupta, Amod

2006-09-01

To compare the ultrasound biomicroscopic measurement of the anterior chamber angle in Asian Indian eyes, with the angle width estimated by gonioscopy. Patients with open and closed angles attending a glaucoma clinic were recruited for the study. Temporal quadrants of the angles of patients were categorized by gonioscopy as Grade 0 to Grade 4, using Shaffer's classification. These angles were quantified by ultrasound biomicroscopy (UBM) using the following biometric characteristics: Angle opening distance at 250 micro (AOD 250) and 500 micro (AOD 500) from the scleral spur and trabecular meshwork-ciliary process distance (TCPD). The angles were further segregated as "narrow angles" (Schaffer's Grade 2 or less) and "open angles" (Schaffer's Grade 3 and 4). The UBM measurements were computed in each case and analyzed in relation to the gonioscopic angle evaluation. One hundred and sixty three eyes of 163 patients were analyzed. One hundred and six eyes had "narrow angles" and 57 eyes had "open angles" on gonioscopy. There was a significant difference among the mean UBM measurements of each angle grade estimated by gonioscopy (P < 0.001). The Pearson correlation coefficient between all UBM parameters and gonioscopy grades was significant at the 0.01 level. The mean AOD 250, AOD 500 and TCPD in narrow angles were 58+/-49 micro, 102+/-84 micro and 653+/-124 respectively, while it was 176+/-47 micro, 291+/-62 micro and 883+/-94 micro in eyes with open angles (P < 0.001) respectively. The angle width estimated by gonioscopy correlated significantly with the angle dimensions measured by UBM. Gonioscopy, though a subjective test, is a reliable method for estimation of the angle width.

Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

PubMed

Marshall, P E; Goldsmith, P C

1980-07-14

The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

12 CFR 614.4265 - Real property evaluations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Real property evaluations. 614.4265 Section 614... Collateral Evaluation Requirements § 614.4265 Real property evaluations. (a) Real estate shall be valued on... property and operation where the transaction value exceeds $250,000 and the real estate taken as collateral...

12 CFR 614.4265 - Real property evaluations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Real property evaluations. 614.4265 Section 614... Collateral Evaluation Requirements § 614.4265 Real property evaluations. (a) Real estate shall be valued on... property and operation where the transaction value exceeds $250,000 and the real estate taken as collateral...

12 CFR 614.4265 - Real property evaluations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Real property evaluations. 614.4265 Section 614... Collateral Evaluation Requirements § 614.4265 Real property evaluations. (a) Real estate shall be valued on... property and operation where the transaction value exceeds $250,000 and the real estate taken as collateral...

12 CFR 614.4265 - Real property evaluations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Real property evaluations. 614.4265 Section 614... Collateral Evaluation Requirements § 614.4265 Real property evaluations. (a) Real estate shall be valued on... property and operation where the transaction value exceeds $250,000 and the real estate taken as collateral...

12 CFR 614.4265 - Real property evaluations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Real property evaluations. 614.4265 Section 614... Collateral Evaluation Requirements § 614.4265 Real property evaluations. (a) Real estate shall be valued on... property and operation where the transaction value exceeds $250,000 and the real estate taken as collateral...

12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

Code of Federal Regulations, 2013 CFR

2013-01-01

... § 221.117 When bank in “good faith” has not relied on stock as collateral. (a) The Board has received... be “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not...

12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

Code of Federal Regulations, 2011 CFR

2011-01-01

... bank in “good faith” has not relied on stock as collateral. (a) The Board has received questions... “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not relied upon...

12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

Code of Federal Regulations, 2014 CFR

2014-01-01

... § 221.117 When bank in “good faith” has not relied on stock as collateral. (a) The Board has received... be “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not...

12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

Code of Federal Regulations, 2012 CFR

2012-01-01

... bank in “good faith” has not relied on stock as collateral. (a) The Board has received questions... “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not relied upon...

12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... bank in “good faith” has not relied on stock as collateral. (a) The Board has received questions... “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not relied upon...

10 CFR 611.108 - Perfection of liens and preservation of collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Perfection of liens and preservation of collateral. 611.108 Section 611.108 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM Direct Loan Program § 611.108 Perfection of liens and preservation...

75 FR 24549 - Merchant Marine Act and Magnuson-Stevens Fishery Conservation and Management Act (Magnuson...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... interests in other collateral to bring credit risk to acceptable levels. Such guarantees or collateral may... level fishermen.'' IFQ financing is fishery specific, and individual Fishery Management Councils (FMCs... ``small vessels'' and ``entry level fishermen''). Under the legislation, the FFP cannot initiate or...

12 CFR 550.320 - What is acceptable collateral for uninsured deposits?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What is acceptable collateral for uninsured deposits? 550.320 Section 550.320 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FIDUCIARY POWERS OF SAVINGS ASSOCIATIONS Exercising Fiduciary Powers Funds Awaiting Investment Or...

Sprain of the short radial collateral ligament in a racing greyhound.

PubMed

Guilliard, M J; Mayo, A K

2000-04-01

Severe carpal lameness in a racing greyhound due to a sprain of the straight part of the short radial collateral ligament is described. The dog subsequently developed an enthesiopathy at the origin of the ligament. Treatment was by kennel rest and the dog returned to successful racing.

31 CFR 203.21 - Collateral security requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Collateral security requirements. 203.21 Section 203.21 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... hereunder; or (iv) The depositary is closed for business by regulatory action or by proper corporate action...

7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... loan is reasonably assured when considered with the integrity and ability of project management... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... and current (not over 90 days old) credit report, proven management, evidence of the market necessary...

7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... loan is reasonably assured when considered with the integrity and ability of project management... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... and current (not over 90 days old) credit report, proven management, evidence of the market necessary...

7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... loan is reasonably assured when considered with the integrity and ability of project management... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... and current (not over 90 days old) credit report, proven management, evidence of the market necessary...

7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... loan is reasonably assured when considered with the integrity and ability of project management... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... and current (not over 90 days old) credit report, proven management, evidence of the market necessary...

7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... loan is reasonably assured when considered with the integrity and ability of project management... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... and current (not over 90 days old) credit report, proven management, evidence of the market necessary...

7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Warehouse-stored marketing assistance loan collateral. 1421.106 Section 1421.106 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS GRAINS AND SIMILARLY HANDLED COMMODITIES-MARKETING...

45 CFR 30.16 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fails to pay the debt(s) within a reasonable time after demand and if such action is in the best interests of the United States. (2) Collection from other sources, including liquidation of security or... will liquidate security or collateral through the exercise of a power of sale in the security...

7 CFR 3560.61 - Loan security.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Loan security. 3560.61 Section 3560.61 Agriculture... DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Direct Loan and Grant Origination § 3560.61 Loan security... collateral. (2) The amount of the loan against the collateral does not exceed its estimated security value...

7 CFR 1427.1088 - Contract fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... storage and handling of CCC-owned cotton or cotton pledged to CCC as loan collateral must pay an annual... storage and handling of CCC-owned cotton or cotton pledged to CCC as loan collateral but who desires such... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Standards for Approval of Warehouses for...

27 CFR 25.98 - Surety or security.

Code of Federal Regulations, 2012 CFR

2012-04-01

... coverage. Bonds required by this part will be given with corporate surety or collateral security. (b... limitations set forth for corporate security by the Secretary which are set forth in the current revision of... penal sum of the bond. (e) Deposit of collateral securities in lieu of corporate surety. Bonds or notes...

27 CFR 25.98 - Surety or security.

Code of Federal Regulations, 2013 CFR

2013-04-01

... coverage. Bonds required by this part will be given with corporate surety or collateral security. (b... limitations set forth for corporate security by the Secretary which are set forth in the current revision of... penal sum of the bond. (e) Deposit of collateral securities in lieu of corporate surety. Bonds or notes...

27 CFR 25.98 - Surety or security.

Code of Federal Regulations, 2010 CFR

2010-04-01

... coverage. Bonds required by this part will be given with corporate surety or collateral security. (b... limitations set forth for corporate security by the Secretary which are set forth in the current revision of... penal sum of the bond. (e) Deposit of collateral securities in lieu of corporate surety. Bonds or notes...

27 CFR 25.98 - Surety or security.

Code of Federal Regulations, 2011 CFR

2011-04-01

... coverage. Bonds required by this part will be given with corporate surety or collateral security. (b... limitations set forth for corporate security by the Secretary which are set forth in the current revision of... penal sum of the bond. (e) Deposit of collateral securities in lieu of corporate surety. Bonds or notes...

27 CFR 25.98 - Surety or security.

Code of Federal Regulations, 2014 CFR

2014-04-01

... coverage. Bonds required by this part will be given with corporate surety or collateral security. (b... limitations set forth for corporate security by the Secretary which are set forth in the current revision of... penal sum of the bond. (e) Deposit of collateral securities in lieu of corporate surety. Bonds or notes...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

31 CFR 901.7 - Liquidation of collateral.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reasonable time after demand and if such action is in the best interest of the United States. Collection from... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Liquidation of collateral. 901.7 Section 901.7 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FEDERAL...

12 CFR 3.37 - Collateralized transactions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... this section: (i) A national bank or Federal savings association may assign a zero percent risk weight... qualifies for a zero percent risk weight under § 3.32. (iii) A national bank or Federal savings association may assign a zero percent risk weight to the collateralized portion of an exposure where: (A) The...

12 CFR 308.17 - Collateral attacks on adjudicatory proceeding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Collateral attacks on adjudicatory proceeding. 308.17 Section 308.17 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF... shall continue without regard to the pendency of that court proceeding. No default or other failure to...

12 CFR 1780.16 - Collateral attacks on adjudicatory proceeding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Collateral attacks on adjudicatory proceeding. 1780.16 Section 1780.16 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF... adjudicatory proceeding shall continue without regard to the pendency of that court proceeding. No default or...

12 CFR 263.17 - Collateral attacks on adjudicatory proceeding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Collateral attacks on adjudicatory proceeding. 263.17 Section 263.17 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE... proceeding shall continue without regard to the pendency of that court proceeding. No default or other...

7 CFR 1427.10 - Approved storage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Approved storage. 1427.10 Section 1427.10 Agriculture... § 1427.10 Approved storage. (a) Eligible cotton may be pledged as collateral for loans only if stored at... warehouse. (c) An approved cotton storage warehouse may temporarily store cotton pledged as collateral for a...

7 CFR 1427.10 - Approved storage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Approved storage. 1427.10 Section 1427.10 Agriculture... § 1427.10 Approved storage. (a) Eligible cotton may be pledged as collateral for loans only if stored at... warehouse. (c) An approved cotton storage warehouse may temporarily store cotton pledged as collateral for a...

7 CFR 1427.10 - Approved storage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Approved storage. 1427.10 Section 1427.10 Agriculture... § 1427.10 Approved storage. (a) Eligible cotton may be pledged as collateral for loans only if stored at... warehouse. (c) An approved cotton storage warehouse may temporarily store cotton pledged as collateral for a...

7 CFR 1427.10 - Approved storage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Approved storage. 1427.10 Section 1427.10 Agriculture... § 1427.10 Approved storage. (a) Eligible cotton may be pledged as collateral for loans only if stored at... warehouse. (c) An approved cotton storage warehouse may temporarily store cotton pledged as collateral for a...

7 CFR 1427.10 - Approved storage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Approved storage. 1427.10 Section 1427.10 Agriculture... § 1427.10 Approved storage. (a) Eligible cotton may be pledged as collateral for loans only if stored at... warehouse. (c) An approved cotton storage warehouse may temporarily store cotton pledged as collateral for a...

12 CFR 950.7 - Collateral.

Code of Federal Regulations, 2010 CFR

2010-01-01

... board of directors of the Bank has specifically approved such acceptance by formal resolution, and the... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Collateral. 950.7 Section 950.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK ASSETS AND OFF-BALANCE SHEET ITEMS ADVANCES...

13 CFR 120.349 - Collateral.

Code of Federal Regulations, 2013 CFR

2013-01-01

....349 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans International Trade Loans § 120.349 Collateral. Each IT loan must be secured either by a first lien position or first mortgage on the property or equipment financed by the IT loan or on other assets of the Borrower...

13 CFR 120.349 - Collateral.

Code of Federal Regulations, 2014 CFR

2014-01-01

....349 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Special Purpose Loans International Trade Loans § 120.349 Collateral. Each IT loan must be secured either by a first lien position or first mortgage on the property or equipment financed by the IT loan or on other assets of the Borrower...

7 CFR 1434.12 - Liens.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FOR HONEY § 1434.12 Liens. (a) CCC's security interest in the honey pledged as collateral is first and... law, all financing statements needed to perfect a security interest in honey pledged as collateral for... security interests, liens, or encumbrances on the honey, CCC shall obtain waivers that fully protect the...

7 CFR 1434.12 - Liens.

Code of Federal Regulations, 2011 CFR

2011-01-01

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Regulation of coronary blood flow during exercise.

PubMed

Duncker, Dirk J; Bache, Robert J

2008-07-01

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.

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