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PubMed2004

Ion generation in a low-density plastic foam by interaction with intense femtosecond laser pulses.

Energetic proton generation in low-density plastic (C5H10) foam by intense femtosecond laser pulse irradiation has been studied experimentally and numerically. Plastic foam was successfully produced by a sol-gel method, achieving an average density of 10 mg/cm(3). The foam target was irradiated by 100 fs pulses of a laser intensity 1 x 10(18) W/cm(2). A plateau structure extending up to 200 keV was observed in the energy distribution of protons generated from the foam target, with the plateau shape well explained by Coulomb explosion of lamella in the foam. The laser-foam interaction and ion generation were studied qualitatively by two-dimensional particle-in-cell simulations, which indicated that energetic protons are mainly generated by the Coulomb explosion. From the results, the efficiency of energetic ion generation in a low-density foam target by Coulomb explosion is expected to be higher than in a gas-cluster target.

Journal Article↗
PubMed1984

Detection of lactoferrin and myeloperoxidase release from single neutrophils by a protein A plaque assay.

A haemolytic plaque assay was adopted to detect release of lactoferrin and myeloperoxidase (MPO) from single neutrophils. Target erythrocytes coated with protein A were bound as a monolayer by poly-L-lysine to the surface of a plastic dish. Secreted lactoferrin and MPO induced plaque formation dependent on the reaction with complement and specific antiserum producing lysis of the protein-A-coated sheep red blood cells. Lactoferrin was found to be released spontaneously from a fraction of neutrophils while MPO was released only after phagocytosis, reflecting different mechanisms for degranulation of MPO-containing azurophil and lactoferrin-containing specific granules.

Antibody-Producing Cells↗
PubMed1991

Dorsal Horn Plasticity Following Re-routeing of Peripheral Nerves: Evidence for Tissue-Specific Neurotrophic Influences from the Periphery.

Some properties of primary sensory neurons change when they reinnervate new peripheral targets (McMahon et al., Neuroscience, 33, 67 - 75, 1989). We ask here if such influences can extend to the central connectivity of sensory neurons. In adult rats the nerve to the gastrocnemius muscle (GN) and the cutaneous sural nerve (SN) were self- and cross-anastomosed on left- and right-hand sides, respectively, so that they regenerated to either appropriate or inappropriate targets. Ten to 14 weeks later, the distribution and strength of spinal connections of the SN and GN were determined. The unmyelinated afferents in the GN innervating skin increased their connectivity to 286% of that seen for the GN innervating muscle (P < 0.005), and came to resemble normal cutaneous afferents. However, for the SN there was no significant difference between appropriately and inappropriately regenerated nerves by this measure. The ability of myelinated fibres to produce inhibitions and facilitations in dorsal horn cells was also assessed. The intact or self-anastomosed SN produced predominantly inhibitory effects, whilst the GN produced predominantly facilitatory effects. After the SN had regenerated to muscle its central effects became predominantly facilitatory, whilst those of the GN innervating skin became inhibitory. These changes were statistically significant. In conclusion, we have found that major changes in the physiology of central connections in the dorsal horn may occur following peripheral reinnervation of foreign targets. The changes that were seen were appropriate to the new target, and could not easily be explained by non-specific changes due to axotomy, or changes in A-fibre-mediated inhibitions. We suggest that these effects might arise because of trophic influences arising in and specific to different peripheral targets.

Journal Article↗
PubMed2004

Basic advances and new avenues in therapy of spinal cord injury.

The prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation.

Animals↗
PubMed1995

Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills.

1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

The molecular chaperone hsp70 interacts with the cytosolic II-III loop of the Cav2.3 E-type voltage-gated Ca2+ channel.

Multiple types of voltage-activated Ca2+ channels (T, L, N, P, Q, R type) coexist in excitable cells and participate in synaptic differentiation, secretion, transmitter release, and neuronal plasticity. Ca2+ ions entering cells trigger these events through their interaction with the ion channel itself or through Ca2+ binding to target proteins initiating signalling cascades at cytosolic loops of the ion conducting subunit (Cava1). These loops interact with target proteins in a Ca2+-dependent or independent manner. In Cav2.3-containing channels the cytosolic linker between domains II and III confers a novel Ca2+ sensitivity to E-type Ca2+ channels including phorbol ester sensitive signalling via protein kinase C (PKC) in Cav2.3 transfected HEK-293 cells. To understand Ca2+ and phorbol ester mediated activation of Cav2.3 Ca2+ channels, protein interaction partners of the II-III loop were identified. FLAG-tagged II-III - loop of human Cav2.3 was over-expressed in HEK 293 cells, and the molecular chaperone hsp70, which is known to interact with PKC, was identified as a novel functional interaction partner. Immunopurified II-III loop-protein of neuronal and endocrine Cav2.3 splice variants stimulate autophosphorylation of PKCa, leading to the suggestion that hsp70--binding to the II-III loop--may act as an adaptor for Ca2+ dependent targeting of PKC to E-type Ca2+ channels.

Amino Acid Sequence↗
PubMed2004

Two Loci of expression for long-term depression at hippocampal mossy fiber-interneuron synapses.

Two distinct forms of long-term depression (LTD) exist at mossy fiber synapses between dentate gyrus granule cells and hippocampal CA3 stratum lucidum interneurons. Although induction of each form of LTD requires an elevation of postsynaptic intracellular Ca2+, at Ca2+-impermeable AMPA receptor (CI-AMPAR) synapses, induction is NMDA receptor (NMDAR) dependent, whereas LTD at Ca2+-permeable AMPA receptor (CP-AMPAR) synapses is NMDAR independent. However, the expression locus of either form of LTD is not known. Using a number of criteria, including the coefficient of variation, paired-pulse ratio, AMPA-NMDA receptor activity, and the low-affinity AMPAR antagonist gamma-D-glutamyl-glycine, we demonstrate that LTD expression at CP-AMPAR synapses is presynaptic and results from reduced transmitter release, whereas LTD expression at CI-AMPAR synapses is postsynaptic. The N-ethylmaleimide-sensitive fusion protein-AP2-clathrin adaptor protein 2 inhibitory peptide pep2m occluded LTD expression at CI-AMPAR synapses but not at CP-AMPAR synapses, confirming that CI-AMPAR LTD involves postsynaptic AMPAR trafficking. Thus, mossy fiber innervation of CA3 stratum lucidum interneurons occurs via two parallel systems targeted to either Ca2+-permeable or Ca2+-impermeable AMPA receptors, each with a distinct expression locus for long-term synaptic plasticity.

Animals↗
PubMed2005

Activity-dependent synapse modulation and the pathogenesis of Alzheimer disease.

During normal development of the nervous system, a major reduction occurs in the initially excessive number of neurons and synapses. This "pruning" process is heavily influenced by patterns of electrical activity in the synaptic circuits being pruned. Many of the cell biological and molecular mechanisms involved in this activity-dependent modification of nervous system structure and function have been explicated, and the area is one of intense study. Similarly, an explosive increase has occurred in knowledge about the molecular pathogenesis of Alzheimer disease (AD). There are significant mechanistic commonalities between the normal neurodevelopmental process and development of AD. We hypothesize that abnormalities in neural activity patterns, or in the coupling between neural activity and maintenance of neurons and synaptic circuits, may be a key determinant in the pathogenesis of AD that is late in onset, sporadic in nature, and in which the genes for the presenilins and the beta amyloid precursor protein are normal. Behavioral data suggests that an active, socially engaged life-style may be associated with a reduced risk for AD. If so, mechanisms linking neural activity with synaptic circuit integrity are probably involved and provide a target for ameliorative pharmacological intervention.

Alzheimer Disease↗
PubMed2006

Neuroserpin.

Neuroserpin is a member of the serpin family of serine protease inhibitors. Tissue distribution analysis reveals a predominantly neuronal expression during the late stages of neurogenesis and, in the adult brain, in areas where synaptic changes are associated with learning and memory (synaptic plasticity). In vitro studies revealed complex formation between neuroserpin and different serine proteases, i.e. tPA, uPA, and plasmin. The neuroserpin-target complex has so far not been characterized in vivo. However, some investigations help to understand the functional role of this serpin. Neuroserpin was shown to be involved in the regulation of the morphology of neuroendocrine cells in culture, possibly by modulating the degradation of the extracellular matrix by proteolytic enzymes such as tPA. Moreover, a role of neuroserpin in mood regulation has been deduced from the over- and underexpression of neuroserpin in genetically modified mice, which showed increased anxiety and novelty-induced hypo-locomotion. In pathological conditions of the central nervous system (i.e. stroke and seizures), neuroserpin plays a neuroprotective role, probably by blocking the deleterious effects of tPA. A familial form of a neurodegenerative disease, termed familial encephalopathy with neuroserpin inclusion bodies, is caused by point mutations in the neuroserpin gene. This condition is characterized by the intracellular polymerization and accumulation of mutated neuroserpin, leading to neuronal death and dementia.

Animals↗
PubMedDate not supplied

Brain attack: a new approach to stroke.

'Brain' attack' is a new term to describe the acute presentation of stroke which emphasises the need for urgent action. The article describes the basis for this new approach to acute stroke treatment. Rational treatment requires individual causes of stroke to be identified early and treatment targeted at the mechanism. Acute stroke treatment aims to preserve the ischaemic penumbra, protect neurons against further ischaemia and enhance brain plasticity to maximise recovery. There is a strong evidence base supporting the routine use of aspirin, but not heparin, in acute ischaemic stroke. There is also convincing evidence supporting intravenous thrombolysis using recombinant tissue plasminogen activator in selected patients within 3 hours of stroke onset. Surprisingly, as many as 33% of suspected-stroke patients arrive in Accident & Emergency departments in the UK within 3 hours of onset. New techniques in MR imaging, particularly diffusion weighted imaging, are transforming the approach to diagnosis of acute stroke. Although neuroprotective drugs have proved disappointing, active neuroprotection in acute stroke should include control of blood pressure within certain limits, antipyretic therapy, maintenance of blood glucose, and early feeding and fluid replacement. Surgical hemicraniectomy should be considered in patients with malignant cerebral oedema. There is good evidence that the best way to enhance recovery from stroke is to admit the patient to a stroke unit. To enable patients to benefit from the early active approach outlined in the article, the following are needed: the development of acute stroke units; imaging protocols; and education of patients, general practitioners and the ambulance services. Stroke care has become a specialised field, requiring input from stroke physicians, as well as the multidisciplinary rehabilitation team. The British Association of Stroke Physicians (BASP) has therefore developed a curriculum which is designed to lead to the development of a new sub-specialty of stroke medicine.

Animals↗
PubMed2004

[Neuroprotection in brain ischemia--doubts and hopes].

In ischaemic stroke the two major potential therapeutic strategies are aimed at either improving cerebral blood flow or directly interacting with the cytotoxic cascade--a large body of evidence gained from animal studies is in support of them. In clinical trials direct neuroprotection by blocking the neurotoxic cascade remained ineffective, although there are several clinical trials still in progress. We summarize the experimental data and present the results of clinical trials and also discuss why so many drugs, which were effective in animal studies, failed in human trials. It is emphasized, that 1. in most animal studies the reduction of infarct size, i.e. the amount of saved penumbral tissue, was the outcome measure, whereas neurological function remained unassessed; 2. the recovery of intellectual performance and higher cortical functions are of major importance in the future quality of life in stroke victims; however, it is impossible to examine these parameters appropriately in animal studies; 3. in many clinical trials the patient population was rather heterogenous and low in number, the study protocol was not optimal and the critical analysis of the subacute and chronic phase was lacking or insufficient. We present the major experimental stroke models, discuss their similarities, differences and limitations as compared to the human pathophysiological processes. The pitfalls of extrapolating data from animal studies to clinical practice are also summarized. The complex network of functional and morphological intercellular connections, the long timescale of neurotoxic and reparative events and the lessons learned from clinical trials suggest, that the use of drug combinations (therapeutic cocktails) targeting multiple steps of the neurotoxic cascade would hopefully result in more effective treatment of ischaemic stroke. Strategies to facilitate brain plasticity and regeneration is an additional promising tool to enhance recovery in brain ischaemia.

Animals↗
PubMed1980

Subarachnoid-pleural fistula.

This is the tenth case report of a subarchnoid-pleural fistula. One of the authors (H. T. L.) reported the first case in 1959. This case reconfirms the value of myelography in making the diagnosis and localizing the surgical target. In addition, it demonstrates the usefullness of the Risa-131 scanning techniques for this condition. The use of methyl methacrylate plastic adhesive for closure of such a fistula has not been previously reported.

Adult↗
PubMed1983

Tumour cell toxicity for the targets of natural killer cells.

Cells of intraperitoneally transplanted murine leukaemias and sarcomas (L-1210, EL-4, MC-11 and SA-1), were found to be toxic for target cells usually employed for assaying NK cells (K-562, EL-4, YAC-1). The 3H-uridine-ribonuclease method used in our study, in contrast to the 51Cr assay, revealed not only cytotoxicity but also reversible damage to target cell membrane (membrane toxicity). This damage became irreversible if target cells had been pretreated with actinomycin D. To exclude the possible role of an admixture of NK, macrophages and T killer cells, contaminants were removed from suspensions of peritoneal tumour cells from syngeneic mice by adherence to plastic surfaces and separation on Hypaque-Ficoll, and from tumour cells grown in vivo or in vitro and then maintained in allogeneic animals by additional treatment with anti-H-2 sera and complement. The toxic effect depended directly on the dosage of tumour cells. Unlabelled target cells inhibited tumour cell toxicity. The medium used for incubating tumour cells was not toxic for target cells.

Animals↗
PubMed2003

A novel control process of cyanobacterial bloom using cyanobacteriolytic bacteria immobilized in floating biodegradable plastic carriers.

A process using a floating carrier for immobilization of cyanobacteriolytic bacteria, B.cereus N-14, was proposed to realize an effective in situ control of natural floating cyanobacterial blooms. The critical concentrations of the cyanobacteriolytic substance and B.cereus N-14 cells required to exhibit cyanobacteriolytic activity were investigated. The results indicated the necessity of cell growth to produce sufficiently high amounts of the cyanobacteriolytic substance to exhibit its activity and also for conditions enabling good contact between high concentrations of the cyanobacteriolytic substance and cyanobacteria. Floating biodegradable plastics made of starch were applied as a carrier material to maintain close contact between the immobilized cyanobacteriolytic bacteria and floating cyanobacteria. The floating starch-carriers could eliminate 99% of floating cyanobacteria in 4 d. Since B.cereus N-14 could produce the cyanobacteriolytic substance under the presence of starch and some amino acids, the cyanobacteriolytic activity could be attributed to carbon source fed from starch carrier and amino acids eluted from lysed cyanobacteria. Therefore, the effect of using a floating starch-carrier was confirmed from both view points as a carrier for immobilization and a nutrient source to stimulate cyanobacteriolytic activity. The new concept to apply a floating carrier immobilizing useful microorganisms for intensive treatment of a nuisance floating target was demonstrated.

Biocompatible Materials↗
PubMed2005

Lipids and drugs of abuse.

Drug abuse continues to take an enormous economic and social toll on the world. Among the costs are reduced productivity, increased need for medical services and stress on families. Treatments that allow affected individuals to reduce compulsive drug use are lacking and novel approaches to their development will likely come from increased understanding of the consequences of chronic exposure to reinforcing drugs. The purpose of this review is to explore the role of lipids in drug abuse and to present a rationale for an increased focus on the interactions between drugs of abuse and lipids in the brain. Small molecular weight lipids function as neuromodulators in the brain and, as such, play a role in the synaptic plasticity that occurs following exposure to drugs of abuse. In addition, the membrane lipid bilayer consists of lipid subdomains and emerging evidence suggests that protein function can be altered by transient associations with these subdomains. Finally, lipidomics is a very new field devoted to the exploration of changes in cellular lipid constituents during phenotypic alterations. Enhanced research in all of these areas will likely provide useful insights into and, perhaps, therapeutic targets for the treatment of drug abuse.

Arachidonic Acids↗
PubMed2006

Plasticity of brainstem mechanisms of cough.

The cough reflex is a brainstem reflex, consisting of specific sensory afferent nerves which trigger the reflex, by transmitting the sensory input over vagal or laryngeal nerves to a brainstem circuitry which processes and ultimately transforms the sensory input into a complex motor output to generate cough. The first synaptic target for the primary cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS). This position in the reflex pathway and intricate local circuits within the nucleus make it a strategic site where the sensory information can be modified. Plasticity at this synapse will change the nature of the output--exaggerating it, suppressing it or transforming it into some other complex pattern. This review integrates evidence implicating the NTS in exaggerated cough with proof of the concept that NTS neurons undergo plasticity to contribute to an exaggeration of cough.

Afferent Pathways↗
PubMed1997

Short- and long-term plasticity of the hippocampus to nucleus accumbens and prefrontal cortex pathways in the rat, in vivo.

The pathways from the hippocampal formation to the nucleus accumbens and the prefrontal cortex are likely to play a role in several aspects of learning and memory. In the present study we addressed the question of how plastic changes in these structures may occur simultaneously. This question can be studied in an appropriate way in the hippocampal/fornix-fimbria to prefrontal cortex/nucleus accumbens system, since electrical stimulation of the fornix-fimbria fibre bundle evokes characteristic field potentials in the two target areas simultaneously. First, we examined the termination field in the nucleus accumbens (medial shell and core region with an extension into the ventro-medial caudate-putamen) and the prefrontal cortex (deeper layers of the ventral prelimbic and ventral infralimbic areas) by recording single unit activity evoked by stimulation of fornix-fimbria fibres in halothane anaesthetized rats. Second, we studied short-term plasticity, namely paired pulse facilitation, in these two areas upon stimulation of the fornix-fimbria fibres. In the nucleus accumbens, paired pulse facilitation was encountered for double pulse intervals between 25 and 500 ms, peaking around 100 ms. In the medial prefrontal cortex it was confined to intervals between 25 and 200 ms, with a peak around 75 ms. Third, we investigated whether LTP could be elicited simultaneously in the two target structures by a single tetanic stimulation (50 Hz, 2 s) of the fornix-fimbria fibres. LTP that was sustained for more than 90 min in the medial prefrontal cortex, reached levels of 130% of control values. In the nucleus accumbens, however, only a transient form of potentiation was found which lasted no more than 60 min. These data show that synaptic weights can be changed in several target structures of the hippocampal formation, simultaneously, in a distributed way.

Animals↗
PubMed1983

In vitro detection of cell-mediated immunity to individual tumor-specific antigens of chemically induced BALB/c fibrosarcomas.

In this study we have analyzed the in vitro cell-mediated cytotoxicity of immune peritoneal exudate cells (PEC), elicited in syngeneic mice against the MCA-induced, TSTA-bearing BALB/c fibrosarcoma CA-2, GI-17 and C-3. The 4 h 51Cr-release assay showed the immune PEC effectors to be specifically cytotoxic to fibrosarcoma used for the immunization, but not to other syngeneic MCA-induced tumors or normal fibroblasts. Cold target inhibition experiments on CA-2 cells confirmed the specificity of the reaction. When PEC, lymph-node and spleen cells from BALB/c anti-CA-2 mice were compared for anti-tumor activity, only PEC were found to kill tumor cells significantly. PEC effectors did not have a significant level of NK or NC activities since they were unable to destroy YAC-1 or WEHI-164 tumor cells. PEC anti-CA-2 were analyzed for the expression of T-cell markers by anti-Thy 1.2, anti-Ly 1.2 and Ly 2.2 monoclonal antibodies. Anti-tumor specific effector cells were identified as mature T cells since they were not adherent to plastic and showed Thy 1.2+, Ly 1.2- and Ly 2.2+ phenotypes. In addition, anti-H-2Kd but not anti-H-2Dd alloantiserum added to target cells, blocked CA-2 tumor lysis, thus supporting the conclusion that the T-cell response against TSTA is H-2 restricted.

Animals↗