Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia

Background

Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation which has been shown to alter cortical excitability in the upper limb representation of primary somatosensory cortex (SI). However, it is unknown whether cTBS modulates cortical excitability within the lower limb representation in SI. The present study investigates the effects of cTBS over the SI lower limb representation on cortical somatosensory evoked potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve stimulation at the knee. SEPs and H-reflex were recorded before and in four time blocks up to 30 minutes following cTBS targeting the lower limb representation within SI.

Results

Following cTBS, the P1-N1 first cortical potential was significantly decreased at 12?C16 minutes. CTBS also suppressed the P2-N2 second cortical potential for up to 30 minutes following stimulation. The H-reflex remained statistically unchanged following cTBS although there was a modest suppression observed.

Conclusion

We conclude that cTBS decreases cortical excitability of the lower limb representation of SI as evidenced by suppressed SEP amplitude. The duration and magnitude of the cTBS after effects are similar to those observed in upper limb studies.     

A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Background

Our goal was to examine the spatiotemporal integration of tactile information in the hand representation of human primary somatosensory cortex (anterior parietal somatosensory areas 3b and 1), secondary somatosensory cortex (S2), and the parietal ventral area (PV), using high-resolution whole-head magnetoencephalography (MEG). To examine representational overlap and adaptation in bilateral somatosensory cortices, we used an oddball paradigm to characterize the representation of the index finger (D2; deviant stimulus) as a function of the location of the standard stimulus in both right- and left-handed subjects.

Results

We found that responses to deviant stimuli presented in the context of standard stimuli with an interstimulus interval (ISI) of 0.33s were significantly and bilaterally attenuated compared to deviant stimulation alone in S2/PV, but not in anterior parietal cortex. This attenuation was dependent upon the distance between the deviant and standard stimuli: greater attenuation was found when the standard was immediately adjacent to the deviant (D3 and D2 respectively), with attenuation decreasing for non-adjacent fingers (D4 and opposite D2). We also found that cutaneous mechanical stimulation consistently elicited not only a strong early contralateral cortical response but also a weak ipsilateral response in anterior parietal cortex. This ipsilateral response appeared an average of 10.7 ± 6.1 ms later than the early contralateral response. In addition, no hemispheric differences either in response amplitude, response latencies or oddball responses were found, independent of handedness.

Conclusion

Our findings are consistent with the large receptive fields and long neuronal recovery cycles that have been described in S2/PV, and suggest that this expression of spatiotemporal integration underlies the complex functions associated with this region. The early ipsilateral response suggests that anterior parietal fields also receive tactile input from the ipsilateral hand. The lack of a hemispheric difference in responses to digit stimulation supports a lack of any functional asymmetry in human somatosensory cortex.     

Temporal mismatch between pain behaviour, skin Nerve Growth Factor and intra-epidermal nerve fibre density in trigeminal neuropathic pain

Background

The neurotrophin Nerve Growth factor (NGF) is known to influence the phenotype of mature nociceptors, for example by altering synthesis of neuropeptides, and changes in NGF levels have been implicated in the pathophysiology of chronic pain conditions such as neuropathic pain. We have tested the hypothesis that after partial nerve injury, NGF accumulates within the skin and causes ‘pro-nociceptive’ phenotypic changes in the remaining population of sensory nerve fibres, which could underpin the development of neuropathic pain.

Results

Eleven days after chronic constriction injury of the rat mental nerve the intra-epidermal nerve fibre density of the chin skin from had reduced from 11.6?±?4.9 fibres/mm to 1.0?±?0.4 fibres/mm; this slowly recovered to 2.4?±?2.0 fibres/mm on day 14 and 4.0?±?0.8 fibres/mm on day 21. Cold hyperalgesia in the ipsilateral lower lip was detectable 11 days after chronic constriction injury, although at this time skin [NGF] did not differ between sides. At 14 days post-injury, there was a significantly greater [NGF] ipsilaterally compared to contralaterally (ipsilateral?=?111?±?23 pg/mg, contralateral?=?69?±?13 pg/mg), but there was no behavioural evidence of neuropathic pain at this time-point. By 21 days post-injury, skin [NGF] was elevated bilaterally and there was a significant increase in the proportion of TrkA-positive (the high-affinity NGF receptor) intra-epidermal nerve fibres that were immunolabelled for the neuropeptide Calcitonin Gene-related peptide.

Conclusions

The temporal mismatch in behaviour, skin [NGF] and phenotypic changes in sensory nerve fibres indicate that increased [NGF] does not cause hyperalgesia after partial mental nerve injury, although it may contribute to the altered neurochemistry of cutaneous nerve fibres.     

The effect of water immersion on short-latency somatosensory evoked potentials in human

Background  

Water immersion therapy is used to treat a variety of cardiovascular, respiratory, and orthopedic conditions. It can also benefit some neurological patients, although little is known about the effects of water immersion on neural activity, including somatosensory processing. To this end, we examined the effect of water immersion on short-latency somatosensory evoked potentials (SEPs) elicited by median nerve stimuli. Short-latency SEP recordings were obtained for ten healthy male volunteers at rest in or out of water at 30°C. Recordings were obtained from nine scalp electrodes according to the 10-20 system. The right median nerve at the wrist was electrically stimulated with the stimulus duration of 0.2 ms at 3 Hz. The intensity of the stimulus was fixed at approximately three times the sensory threshold.     

Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

Background  

Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG) activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP) triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Non-dominant hand movement facilitates the frontal N30 somatosensory evoked potential

Background  

Previous literature has shown that the frontal N30 is increased during movement of the hand contralateral to median nerve stimulation. This finding was a result of non-dominant left hand movement in right-handed participants. It is unclear however if the effect depends upon non-dominant hand movement or if this is a generalized phenomenon across the upper-limbs. This study tests the effect of dominant and non-dominant hand movement upon contralateral frontal and parietal somatosensory evoked potentials (SEPs) and further tests if this relationship persists in left hand dominant participants. Median nerve SEPs were elicited from the wrist contralateral to movement in both right hand and left hand dominant participants alternating the movement hand in separate blocks. Participants were required to volitionally squeeze (~ 20% of a maximal voluntary contraction) a pressure-sensitive bulb every ~3 seconds with the hand contralateral to median nerve stimulation. SEPs were continuously collected during the task and individual traces were grouped into time bins relative to movement according to the timing of components of the Bereitschaftspotential. SEPs were then averaged and quantified from both FCZ and CP3/4 scalp electrode sites during both the squeeze task and at rest.     

Enhancing the effect of repetitive I-wave paired-pulse TMS (iTMS) by adjusting for the individual I-wave periodicity

Background

The aberrant pyramidal tract (APT) refers to the collateral pathway of the pyramidal tract (PT) through the medial lemniscus in the midbrain and pons. Using diffusion tensor tractography (DTT), we investigated the characteristics of the APT in comparison with the PT in the normal human brain.

Results

In thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the 186 hemispheres, the APTs separated from the PT at the upper midbrain level, descended through the medial lemniscus from the midbrain to the pons, and then rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found to originate from the primary somatosensory cortex without a primary motor cortex origin. Values of fractional anisotropy (FA) and tract volume of the APT were lower than those of the PT (P < 0.05); however, no difference in mean diffusivity (MD) value was observed (P > 0.05).

Conclusion

We found that the APT has different characteristics, including less directionality, fewer neural fibers, and less origin from the primary motor cortex than the PT.     

Cortical disinhibition occurs in chronic neuropathic,but not in chronic nociceptive pain

Background  

The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.     

Transcranial Magnetic Stimulation for the treatment of tinnitus: Effects on cortical excitability

Background

Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positron-emission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single- and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitus-questionnaire.

Results

We noted a significant interaction between treatment response and changes in motor cortex excitability during active rTMS. Specifically, clinical improvement was associated with an increase in intracortical inhibition, intracortical facilitation and a prolongation of the cortical silent period. These results indicate that intraindividual changes in cortical excitability may serve as a correlate of response to rTMS treatment.

Conclusion

The observed alterations of cortical excitability suggest that low frequency rTMS may evoke long-term-depression like effects resulting in an improvement of subcortical inhibitory function.     

Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation

Background  

Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS.     

Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study

Background

Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results

We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion

These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.     

Use of ultraviolet-light irradiated multiple myeloma cells as immunogens to generate tumor-specific cytolytic T lymphocytes

Background

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic T lymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity.

Results

By day 10 of cultures, PBMCs primed using UV-irradiated tumor cells demonstrated a higher percentage of activated CD8+/CD4- T lymphocytes than non-primed PBMCs or PBMCs primed using mitomycin-treated MM cells. Cytotoxicity assays revealed that primed PBMCs were markedly more effective (p < 0.01) than non-primed PBMCs in killing RPMI 8226 MM cells. Surface expression of glucose regulated protein 94 (Grp94/Gp96) and Grp78 were both found to be induced in UV-treated MM cells.

Conclusion

Since, HSP-associated peptides are known to mediate tumor rejection; these data suggest that immune-mediated eradication of MM cells could be elicited via a UV-induced HSP process. The finding that the addition of 17-allylamide-17-demethoxygeldanamycin (17AAG, an inhibitor of HSP 90-peptide interactions) resulted in decreased CTL-induced cytotoxicity supported this hypothesis. Our study, therefore, provides the framework for the development of anti-tumor CTL cellular vaccines for treating MM using UV-irradiated tumor cells as immunogens.     

Mass mixing,CP violation and left-right symmetry for heavy neutral mesons

We investigate \(M^0 - \bar M^0 \) mixing and CP violation in the minimal left-right symmetric gauge model with spontaneous P and CP violation. The dominant contributions to the mixing amplitude including QCD corrections are calculated explicitly for \(B^0 - \bar B^0 \) . While the amount of mixing is not much changed with respect to the standard model leftright symmetry can give rise to significantly larger CP violation in the \(B_s^0 - \bar B_s^0 \) system (up to two orders of magnitude for the dilepton charge asymmetry). Sizable CP violating effects require that the left-right contribution to theK _L K _S mass difference has the same sign as the standard model contribution. We also comment on \(D^0 - \bar D^0 \) mixing including a careful discussion of the standard model prediction for the short distance part.     

Confronting the MSSM and the NMSSM with the discovery of a signal in the two photon channel at the LHC

We confront the discovery of a boson decaying into two photons, as reported recently by ATLAS and CMS, with the corresponding predictions in the Minimal Supersymmetric Standard Model (MSSM) and the Next-to-Minimal Supersymmetric Standard Model (NMSSM). We perform a scan over the relevant regions of parameter space in both models and evaluate the MSSM and NMSSM predictions for the dominant Higgs production channel and the photon–photon decay channel. Taking into account the experimental constraints from previous direct searches, flavor physics, electroweak measurements as well as theoretical considerations, we find that a Higgs signal in the two photon channel with a rate equal to, or above, the SM prediction is viable over the full mass range 123?M _H ?127 GeV, both in the MSSM and the NMSSM. We find that besides the interpretation of a possible signal at about 125 GeV in terms of the lightest $\mathcal {CP}$ -even Higgs boson, both the MSSM and the NMSSM permit also a viable interpretation where an observed state at about 125 GeV would correspond to the second-lightest $\mathcal {CP}$ -even Higgs boson in the spectrum, which would be accompanied by another light Higgs with suppressed couplings to W and Z bosons. We find that a significant enhancement of the γγ rate, compatible with the signal strengths observed by ATLAS and CMS, is possible in both the MSSM and the NMSSM, and we analyse in detail different mechanisms in the two models that can give rise to such an enhancement. We briefly discuss also our predictions in the two models for the production and subsequent decay into two photons of a $\mathcal {CP}$ -odd Higgs boson.     

Measuring Dirac CP-violating phase with intermediate energy beta beam facility

We find that spontaneously broken parity ( $P$ ) or left–right symmetry stabilizes dark matter in a beautiful way. If dark matter has a non-real intrinsic parity $\pm i$ (e.g. if it entails Majorana fermions), parity can ensure that it cannot decay to all normal particles with real intrinsic parities. However, if Majorana couplings are absent either in the lepton or the dark sector, $P$ symmetry can be redefined to remove relative non-real intrinsic phases. It is therefore predicted that neutrinos and dark matter fermions must have Majorana masses if dark matter is stable due to parity. The strong CP problem is solved by additionally imposing CP and including vectorlike fermions that help generate CP violation. If leptonlike heavy fermions are provided purely imaginary intrinsic parity phase, they do not couple to the usual leptons, and leptonic CP phases are not generated, which is a testable prediction. Experimentally if leptonic CP phases are not found (if they are consistent with $0$ or $\pi $ ) it can be evidence for the type of models in this work where CP is spontaneously or softly broken and there is also a second hidden or softly broken symmetry such as $P$ , $Z_2$ or $Z_4$ . However, leptonic CP violation can be present in closely related or some non-minimal versions of these models, such as by also including vectorlike leptons with real intrinsic parities.     

Probing Higgs boson — and supersymmetry-induced CP violation in top quark production by (un-) polarized electron-positron collisions

We consider, both for unpolarized and longitudinally polarized electron beams, the reaction $e^ + e^ - \to t\bar t$ with subsequent semileptonict and nonleptonic $\bar t$ decay and vice versa and investigate optimized angular correlations which are sensitive to CP non-conservation in the $t\bar t$ production vertex. We calculate these correlations for two-Higgs-doublet extensions and the minimal super-symmetric extension of the Standard Model (SM) with CP violation beyond the Kobayashi-Maskawa phase. While the sensitivity of the optimal correlation for tracing dispersive CP effects is enhanced with longitudinally polarized electron beams, we find that the sensitivity of the best correlation for probing absorptive CP effects is almost independent of the polarization degree.     

Structural,surface, and electrical properties of nitrogen ion implanted ZnTe epilayers

P-type ZnTe epilayers grown on GaAs (001) by molecular beam epitaxy have been achieved by N ions implantation, and reached a doping level of more than 1  \(\times \)  10 \(^{18}\) cm \(^{-3}\) . X-ray diffraction spectra suggest that increasing the post-implantation annealing temperature can promote the N ions occupying substitutional sites and help to remove the radiation damage.The hole concentration rises with annealing temperature, while the lowest resistivity and the highest mobility can be obtained by annealing at 450  \(^{\circ }\) C for 5 min. Annealing for 1 min cannot obtain low resistivity. Fabricating ZnTe films with a lower VI/II beam equivalent pressure ratio results in an enhancement in hole concentration and a drop of mobility.In addition, p-ZnTe/n-GaAs and p-ZnTe/n-ZnSe/n-GaAs junctions show better rectifying behaviour after ion implantation.     

Optical properties of ZnTe doped with transition metals (Ti, Cr and Mn)

The electronic and optical properties of $\text{ Zn }_{1-\mathrm{x}}\text{ M }_\mathrm{x}\text{ Te }$ with (M = Cr, Mn, Ti) have been investigated, within generalized gradient approximation (GGA) using the full potential linear augmented plane wave (FP-LAPW) method as implemented in the WIEN2K code. This work presents detailed information about optical properties like absorbance, refractive index and reflectivity. The result of this study shows that doped ZnTe material with Ti, Cr and Mn shift the absorption spectrum and reflection to the infrared spectral domain or to the ultra violet region, depending on the nature of the dopant. Dielectric functions for different compositional alloys are calculated for 16-atom cubic supercell structure. The calculated band gaps are fitted with a linear equation: ( $\upalpha \text{ h }\upnu )^{2} = \text{ A }(\text{ h }\upnu -\text{ Eg }$ ). For all types of doping the position of critical points (CP’s) $\text{ E }_{0}, \text{ E }_{1}$ and $\text{ E }_{2}$ show good agreement with the experimental data.