Preconditioning Stimulation Research Articles

Photobiomodulation at Defined Wavelengths Regulates Mitochondrial Membrane Potential and Redox Balance in Skin Fibroblasts.

Starting from the discovery of phototherapy in the beginning of the last century, photobiomodulation (PBM) has been defined in late 1960s and, since then, widely described in different in vitro models. Robust evidence indicates that the effect of light exposure on the oxidative state of the cells and on mitochondrial dynamics, suggesting a great therapeutic potential. The translational scale-up of PBM, however, has often given contrasting and confusing results, mainly due to light exposure protocols which fail to adequately control or define factors such as emitting device features, emitted light characteristics, exposure time, cell target, and readouts. In this in vitro study, we describe the effects of a strictly controlled light-emitting diode (LED)-based PBM protocol on human fibroblasts, one of the main cells involved in skin care, regeneration, and repair. We used six emitter probes at different wavelengths (440, 525, 645, 660, 780, and 900 nm) with the same irradiance value of 0.1 mW/cm2, evenly distributed over the entire surface of the cell culture well. The PBM was analyzed by three main readouts: (i) mitochondrial potential (MitoTracker Orange staining), (ii) reactive oxygen species (ROS) production (CellROX staining); and (iii) cell death (nuclear morphology). The assay was also implemented by cell-based high-content screening technology, further increasing the reliability of the data. Different exposure protocols were also tested (one, two, or three subsequent 20 s pulsed exposures at 24 hr intervals), and the 645 nm wavelength and single exposure chosen as the most efficient protocol based on the mitochondrial potential readout, further confirmed by mitochondrial fusion quantification. This protocol was then tested for its potential to prevent H2O2-induced oxidative stress, including modulation of the light wave frequency. Finally, we demonstrated that the controlled PBM induced by the LED light exposure generates a preconditioning stimulation of the mitochondrial potential, which protects the cell from oxidative stress damage.

N°184 – Adjuncting Linked Quadri-polar (LQP) and preconditioning stimulation technique to improve TCeMEPs during spinal tumor resection. A case report

N°184 – Adjuncting Linked Quadri-polar (LQP) and preconditioning stimulation technique to improve TCeMEPs during spinal tumor resection. A case report

Transcranial electrical stimulation modifies the neuronal response to psychosocial stress exposure

Stress is a constant characteristic of everyday life in our society, playing a role in triggering several chronic disorders. Therefore, there is an ongoing need to develop new methods in order to manage stress reactions. The regulatory function of right medial-prefrontal cortex (mPFC) is frequently reported by imaging studies during psychosocial stress situations. Here, we examined the effects of inhibitory and excitatory preconditioning stimulation via cathodal and anodal transcranial direct current stimulation (tDCS) on psychosocial stress related behavioral indicators and physiological factors, including the cortisol level in the saliva and changes in brain perfusion. Twenty minutes real or sham tDCS was applied over the right mPFC of healthy subjects before the performance of the Trier Social Stress Test (TSST). Regional cerebral blood flow (rCBF) was measured during stimulation and after TSST, using pseudo-continuous arterial spin labeling (pCASL). Comparing the effect of the different stimulation conditions, during anodal stimulation we found higher rCBF in the right mPFC, compared to the sham and in the right amygdala, superior PFC compared to the cathodal condition. Salivary cortisol levels showed a decrease in the anodal and increase in cathodal groups after completion of the TSST. The behavioral stress indicators indicated the increase of stress level, however, did not show any significant differences among groups. In this study we provide the first insights into the neuronal mechanisms mediating psychosocial stress responses by prefrontal tDCS.

Temporal interaction in electrical hearing elucidates auditory nerve dynamics in humans

In cochlear implants, severe limitations arise from electrical crosstalk between channels. Therefore, the current trend in cochlear implants is to increase stimulation rates to encode signals with higher temporal precision. However, the fundamental question: “What is the limit of temporal precision due to inherent neuronal dynamics of the stimulated neurons?” has not yet been resolved. In this study we have developed a double-pulse method and, for the first time, reversed stimulus polarity systematically between consecutive pulses to elucidate subthreshold-induced temporal interaction effects. This method allowed us to determine the time-course of subthreshold temporal interaction in human subjects which identifies the limits of encoded temporal precision. Our results show significant temporal interaction up to 600 μs inter-pulse interval. In all the cases tested we saw a facilitation effect on threshold. Interaction effects at a 20% below threshold pre-conditioning stimulation showed up to 38% ± 6% threshold reduction. These results imply that there is significant temporal interaction between two subsequent pulses. This interaction diminishes the precision of amplitude coding. We predict interaction effects on temporal precision and channel interaction. For (interleaved) stimulation with short inter-pulse intervals it is interesting to consider our interaction results; and it may become important to consider them for future coding strategies where high temporal precision is required. In an increasing group of binaural implanted patients this will be the case when interaural time differences are encoded with μs precision.

Improved neuromonitoring during spinal surgery using double-train transcranial electrical stimulation.

Motor evoked potentials (MEPs) evoked by transcranial electrical stimulation (TES) have become an important technique for monitoring spinal cord function intra-operatively, but can fail in some patients. A new technique of double-train stimulation is described. A multipulse transcranial electrical stimulus is preceded by a preconditioning pulse train that leads to larger MEP responses. An MEP monitoring system was adapted for double-train transcranial stimulation (DTS). MEP responses from 160 anterior tibial muscles obtained by double-train stimulation were analysed. All patients received propofol/remifentanil/O2/N2O anaesthesia. Fifty-two (83%) out of 63 single-train tibial MEPs with response amplitudes below 100 microV were magnified to over 100 microV, with an inter-train (inter-stimulus) interval ITI = 10-35 ms. These 63 amplitudes were magnified by an overall logarithmic mean factor of 15.5. For 97 MEPs with amplitudes above 100 microV, the logarithmic mean facilitation factor was 2.4. It was concluded that double-train TES stimulation can markedly facilitate responses to a single stimulus train (STS). The facilitation appears to be most effective when the responses to STS would otherwise be small or absent. This preconditioning stimulation technique is therefore useful when an STS leads to responses that are too small for effective monitoring.

Synaptically stimulated induction of group i metabotropic glutamate receptor-dependent long-term depression and depotentiation is inhibited by prior activation of metabotropic glutamate receptors and PROTEIN KINASE C

We have investigated metaplasticity of the group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) and depotentiation (DP) induced by physiological synaptic stimulation in the medial perforant path of the dentate gyrus in vitro. Group I mGluR-LTD/DP was inhibited by prior preconditioning brief high frequency stimulation (HFS) if the preconditioning HFS induced long-term potentiation (LTP) or if the induction of LTP was inhibited by an NMDA receptor antagonist. The inhibitory effect of the preconditioning HFS on LTD/DP was dependent upon activation of mGluRs, as it was blocked by the presence of the mGluR antagonist ( S)-α-methyl-4-carboxyphenylglycine during the preconditioning stimulation. The inhibitory effect of the preconditioning HFS involved stimulation of PKC, as the presence of the PKC inhibitor bisindolylmaleimide (BIS) during the preconditioning stimulation prevented the inhibitory effect of such preconditioning stimulation. Activation of PKC was also necessary for the induction of mGluR-LTD itself, as the PKC inhibitor BIS prevented the induction of the mGluR-LTD. We suggest that the physiological stimulation of mGluRs by the preconditioning stimulation produces a PKC-dependent inactivation of subsequent group I mGluR functioning and thereby an inhibition of induction of group I mGluR-dependent LTD/DP induction.

Activation of group II metabotropic glutamate receptors results in long-term potentiation following preconditioning stimulation in the dentate gyrus

The role of group II metabotropic glutamate receptors in the induction/expression of long-term potentiation has been investigated in the medial perforant path of the outer (infrapyramidal) blade of the rat dentate gyrus in vitro. Activation of group II metabotropic glutamate receptors by perfusion of the selective agonist LY354740 did not induce long-term potentiation or long-term depression in control. However, LY354740, applied following the induction of long-term potentiation by high frequency stimulation, resulted in additional long-term potentiation. LY354740 was only found to cause additional long-term potentiation if the pre-existing high frequency stimulation-induced long-term potentiation was sub-maximal. Although activation of metabotropic glutamate receptors was not required for induction of high frequency stimulation-induced long-term potentiation, activation of both group I and group II metabotropic glutamate receptors was required during high frequency stimulation-induced long-term potentiation in order for subsequent application of LY354740 to result in additional long-term potentiation. Thus, the long-term potentiation caused by application of LY354740 following high frequency-induced long-term potentiation was prevented if the high frequency stimulation was given in the presence of ( S)-α-methyl-4-carboxyphenylglycine or the selective group I or group II metabotropic glutamate receptor antagonists 1-aminoindan-1,5-dicarboxylic acid or (2 S)-α-ethylglutamic acid respectively. The long-term potentiation caused by LY354740 was also dependent upon activation of N-methyl- D-aspartate receptors during the high frequency stimulation, being blocked if high frequency stimulation was given in the presence of the N-methyl- D-aspartate receptor antagonist, D(−)-2-amino-5-phosphonopentanoic acid. The long-term potentiation resulting from activation of group II metabotropic glutamate receptors could be due either to the enhancement of the expression level of the high frequency stimulation-induced long-term potentiation, or alternatively, to a direct novel induction of long-term potentiation. In either theory, the long-term potentiation resulting from activation of group II metabotropic glutamate receptors is dependent upon prestimulation of group I and group II metabotropic glutamate receptors and N-methyl- D-aspartate receptors during the ‘preconditioning high frequency stimulation’.

Stimulation of substantia nigra pars reticulata enhances dentate granule cell excitability

We studied the effects of electrical and chemical stimulation of the substantia nigra (SN) on the dentate granule cell (DGC) response to perforant path stimulation. Studies were carried out in both pentobarbital anesthetized and awake freely moving rats. Chemical stimulation was achieved by microinjection ofN-methyl- d,l-aspartate (NMDA), an excitatory amino acid. Electrical preconditioning stimulation applied to the area of the SN, but not dorsal to SN, increased the excitability of DGCs. Intracerebral microinjection of NMDA into the contralateral SN pars reticulata (SNR), but not into SN pars compacta or cerebral peduncle, also produced a marked and reversible enhancement of DGC excitability. In both instances, the increased DGC excitability consisted of increased amplitude of the perforant path evoked population spike without change in the slope of the population excitatory postsynaptic potential (pEPSP). We interpret the data to indicate that increasing the output of the SNR increases the excitability of the DGCs, a limbic neuronal population regulating information transfer through hippocampal pathways. Together with our previous finding that decreasing the output of SNR suppressed limbic seizures, these data demonstrate that the SNR exerts a powerful influence on limbic system excitability. Delineating the anatomic pathway mediating this influence could provide valuable insight into the mechanisms underlying basal ganglia-limbic interactions in both physiologic and pathologic conditions.

Enhancement of visual responses of area 7 neurons by electrical pre-conditioning stimulation of LP-pulvinar nuclei of the monkey.

The characteristics of visually evoked unit responses in area PG of the infraparietal lobule were studied in the awake trained Rhesus monkey. These responses are shown to be significantly modified by pairing the visual stimulus with pre-conditioning stimulation of targets in the LP Pulvinar complex. Pre-conditioning stimuli were either single pulses, or a 50 ms train of pulses at 100 Hz delivered through bipolar electrodes 20 ms prior to, simultaneously with, or 50 ms following the visual stimulus. In some cases, modifications of the visual responses appeared as more massive discharges; in others they became bursts of constant latencies, pattern and duration, that contained high frequency discharges. A pre-conditioning single stimulus delivered simultaneously to a few sites in the LP, medial and lateral pulvinar was more effective than stimulation at a single electrode site, and produced an enhancement that appeared like an additive effect of several inputs. In the enhanced condition, repetition of single pulse preconditioning stimulation resulted in a considerable build-up of the enhancement. A pre-conditioning train of stimuli delivered during enhancement resulted in a further increase in the constancy of response durations and patterns. These changes, lasting as long as five minutes, manifested hysteresis: when recovery was allowed without any pre-conditioning stimulation, the various response patterns appeared in a reverse order. It is proposed that this dependence of the responses on the neural state is based on a complex network of inputs to cells of area 7.

Posterior parietal manipulation reach neurons with and without visual responsiveness, modifications of their unitary responses by LP pulvinar pre-conditioning stimulation

The corticothalamic projection includes a main, modulatory projection from cortical layer VI terminating with small endings whereas a less numerous, driving projection from layer V forms giant endings. Such dual pattern of corticothalamic projections is well established in rodents and cats for many cortical areas. In non-human primates (monkeys), it has been reported for the primary sensory cortices (A1, V1, S1), the motor and premotor cortical areas and, in the parietal lobe, also for area 7. The present study aimed first at refining the cytoarchitecture parcellation of area 5 into the sub-areas PE and PEa and, second, establishing whether area 5 also exhibits this dual pattern of corticothalamic projection and what is its precise topography. To this aim, the tracer biotinylated dextran amine (BDA) was injected in area PE in one monkey and in area PEa in a second monkey. Area PE sends a major projection terminating with small endings to the thalamic lateral posterior nucleus (LP), ventral posterior lateral nucleus (VPL), medial pulvinar (PuM) and, but fewer, to ventral lateral posterior nucleus, dorsal division (VLpd), central lateral nucleus (CL) and center median nucleus (CM), whereas giant endings formed restricted terminal fields in LP, VPL and PuM. For area PEa, the corticothalamic projection formed by small endings was found mainly in LP, VPL, anterior pulvinar (PuA), lateral pulvinar (PuL), PuM and, to a lesser extent, in ventral posterior inferior nucleus (VPI), CL, mediodorsal nucleus (MD) and CM. Giant endings originating from area PEa formed restricted terminal fields in LP, VPL, PuA, PuM, MD and PuL. Furthermore, the origin of the thalamocortical projections to areas PE and PEa was established, exhibiting clusters of neurons in the same thalamic nuclei as above, in other words predominantly in the caudal thalamus. Via the giant endings CT projection, areas PE and PEa may send feedforward, transthalamic projections to remote cortical areas in the parietal, temporal and frontal lobes contributing to polysensory and sensorimotor integration, relevant for visual guidance of reaching movements for instance.