Magnetogenetic stimulation inside MRI induces spontaneous and evoked changes in neural circuits activity in rats.

The ability to modulate specific neural circuits and simultaneously visualize and measure brain activity with MRI would greatly impact our understanding of brain function in health and disease. The combination of neurostimulation methods and functional MRI in animal models have already shown promise in elucidating fundamental mechanisms associated with brain activity. We developed an innovative magnetogenetics neurostimulation technology that can trigger neural activity through magnetic fields. Similar to other genetic-based neuromodulation methods, magnetogenetics offers cell-, area-, and temporal-specific control of neural activity. The magnetogenetic protein-Electromagnetic Perceptive Gene (EPG)-is activated by non-invasive magnetic fields, providing a unique way to target neural circuits by the MRI static and gradient fields while simultaneously measuring their effect on brain activity. EPG was expressed in rat's visual cortex and the amplitude of low-frequency fluctuation, resting-state functional connectivity (FC), and sensory activation was measured using a 7T MRI. The results demonstrate that EPG-expressing rats had significantly higher signal fluctuations in the visual areas and stronger FC in sensory areas consistent with known anatomical visuosensory and visuomotor connections. This new technology complements the existing neurostimulation toolbox and provides a means to study brain function in a minimally-invasive way which was not possible previously.

Unveiling the role of TRPA1 in cardiovascular health and disease: a mini review.

The transient receptor potential ankyrin 1 (TRPA1) ion channel has emerged as significant regulators of cardiovascular physiology and pathology. TRPA1 is a non-selective cation channel permeable to calcium ions. A unique feature of the channel is its function as a sensor of various temperature, chemical and mechanical stimuli, while it can also be activated by endogenous inflammatory mediators and reactive oxygen species. Over the last two decades, much progress has been made in illuminating the role of TRPA1 in the regulation of cardiovascular physiology and pathophysiology in addition to its important function in pain sensation. This review provides a comprehensive analysis of recent studies investigating the involvement of TRPA1 channels in various cardiovascular diseases, including myocardial infarction, ischemia-reperfusion injury, myocardial fibrosis, and response to environmental toxins. We discuss the diverse roles of TRPA1 channels in cardiac pathology and highlight their potential as therapeutic targets for cardiovascular disorders. Moreover, we explore the challenges and opportunities linked with targeting TRPA1 channels for treating cardiovascular diseases, alongside future research directions.

A novel hybrid Wireless Integrated Sensing Detector for simultaneous EEG and MRI (WISDEM).

Concurrent recording of EEG/fMRI signals reveals cross-scale neurovascular dynamics that are crucial for elucidating fundamental linkage between function and behaviors. However, MRI scanners generate tremendous artifacts for EEG detection. Despite existing denoising methods, cabled connections to EEG receivers are susceptible to environmental fluctuations inside MRI scanners, creating baseline drifts that complicate EEG signal retrieval from the noisy background. Here, a Wireless Integrated Sensing Detector for simultaneous EEG and MRI (WISDEM) is developed to encode fMRI and EEG signals on distinct sidebands of the detector oscillation carrier wave for detection by a standard MRI console over the entire duration of fMRI sequence. Local field potential (LFP) and fMRI maps are retrieved through low-pass and high-pass filtering of frequency-demodulate signals. From optogenetically-stimulated somatosensory cortex, the positive correlation between evoked LFP and fMRI signals validates strong neurovascular coupling, enabling cross-scale brain mapping with this 2-in-1 transducer as a research and diagnostic tool.

Toward Ultra-High-Quality-Factor Wireless Masing Magnetic Resonance Sensing.

It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1-13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio-frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22-fold (to 1,670) via parametric pumping. This active-feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated.

Novel inductively coupled ear-bars (ICEs) to enhance restored fMRI signal from susceptibility compensation in rats.

Functional magnetic resonance imaging faces inherent challenges when applied to deep-brain areas in rodents, e.g. entorhinal cortex, due to the signal loss near the ear cavities induced by susceptibility artifacts and reduced sensitivity induced by the long distance from the surface array coil. Given the pivotal roles of deep brain regions in various diseases, optimized imaging techniques are needed. To mitigate susceptibility-induced signal losses, we introduced baby cream into the middle ear. To enhance the detection sensitivity of deep brain regions, we implemented inductively coupled ear-bars, resulting in approximately a 2-fold increase in sensitivity in entorhinal cortex. Notably, the inductively coupled ear-bar can be seamlessly integrated as an add-on device, without necessitating modifications to the scanner interface. To underscore the versatility of inductively coupled ear-bars, we conducted echo-planner imaging-based task functional magnetic resonance imaging in rats modeling Alzheimer's disease. As a proof of concept, we also demonstrated resting-state-functional magnetic resonance imaging connectivity maps originating from the left entorhinal cortex-a central hub for memory and navigation networks-to amygdala hippocampal area, Insular Cortex, Prelimbic Systems, Cingulate Cortex, Secondary Visual Cortex, and Motor Cortex. This work demonstrates an optimized procedure for acquiring large-scale networks emanating from a previously challenging seed region by conventional magnetic resonance imaging detectors, thereby facilitating improved observation of functional magnetic resonance imaging outcomes.

Stroke prevention and intracranial hemorrhage risk in atrial fibrillation management: A mini review.

This mini-review examines the management of atrial fibrillation (AF) in patients at high risk of bleeding, with a focus on stroke prevention and intracranial hemorrhage risk. Anticoagulant therapy is commonly advised for AF patients, but it can elevate the risk of intracranial hemorrhage in certain individuals prone to bleeding. Two primary perspectives for managing high-risk patients are discussed: adhering to strict anticoagulation therapy or opting for alternative treatments like left atrial appendage closure (LAAC) or aspirin. The benefits and drawbacks of each approach are evaluated, emphasizing the importance of a personalized management plan based on patient risk profiles, comorbidities, and preferences. Ongoing research, including artificial intelligence, advances in LAAC devices, and combination therapies, is explored to enhance stroke prevention and minimize bleeding risk in AF management. A multidisciplinary approach and continuous investigation are vital to achieving better patient outcomes and overall care in this context.

Ultra-Low-Cost Disposable Hand-Held Clinical-Scale Propane Gas Hyperpolarizer for Pulmonary Magnetic Resonance Imaging Sensing.

Hyperpolarized magnetic resonance imaging (MRI) contrast agents are revolutionizing the field of biomedical imaging. Hyperpolarized Xe-129 was recently FDA approved as an inhalable MRI contrast agent for functional lung imaging sensing. Despite success in research settings, modern Xe-129 hyperpolarizers are expensive (up to $1M), large, and complex to site and operate. Moreover, Xe-129 sensing requires specialized MRI hardware that is not commonly available on clinical MRI scanners. Here, we demonstrate that proton-hyperpolarized propane gas can be produced on demand using a disposable, hand-held, clinical-scale hyperpolarizer via parahydrogen-induced polarization, which relies on parahydrogen as a source of hyperpolarization. The device consists of a heterogeneous catalytic reactor connected to a gas mixture storage can containing pressurized hyperpolarization precursors: propylene and parahydrogen (10 bar total pressure). Once the built-in flow valve of the storage can is actuated, the precursors are ejected from the can into a reactor, and a stream of hyperpolarized propane gas is ejected from the reactor. Robust operation of the device is demonstrated for producing proton sensing polarization of 1.2% in a wide range of operational pressures and gas flow rates. We demonstrate that the propylene/parahydrogen gas mixture can retain potency for days in the storage can with a monoexponential decay time constant of 6.0 ± 0.5 days, which is limited by the lifetime of the parahydrogen singlet spin state in the storage container. The utility of the produced sensing agent is demonstrated for phantom imaging on a 3 T clinical MRI scanner located 100 miles from the agent/device preparation site and also for ventilation imaging of excised pig lungs using a 0.35 T clinical MRI scanner. The cost of the device components is less than $35, which we envision can be reduced to less than $5 for mass-scale production. The hyperpolarizer device can be reused, recycled, or disposed.

Evaluation of condylar osseous changes using a wireless detector with proton density-weighted imaging sequences.

Background: Cone-beam computed tomography (CBCT) is the gold standard for evaluating condylar osseous changes. However, the radiation risk and low soft-tissue resolution of CBCT make it unsuitable for evaluating soft tissue such as the articular disc and lateral pterygoid muscle. This study aimed to qualitatively and quantitatively evaluate the feasibility and advantages of using wireless detectors (WD) with proton density-weighted imaging (PDWI) sequences to image condyle changes in patients with temporomandibular disorders (TMD). Methods: This study involved 20 patients (male =8, female =12; mean age 31.65 years, SD 12.68 years) with TMD. All participants underwent a closed oblique sagittal PDWI scan with head/neck coupling coiling (HNCC) and wireless detector-HNCC (WD-HNCC) on a 3.0 T magnetic resonance imaging (MRI) scanner. Subsequently, the changes in the condyle bones in the scanned images for the 2 image types were scored subjectively and compared qualitatively. The contrast-to-noise ratio (CNR) of the 2 types of scanned images was compared quantitatively. The comparison of CNR differences between the 2 types of images was performed using the paired t-test. The kappa statistic was used to test the consistency of quantitative analyses of MRI images between observers. The subjective scores of condylar osseous changes in the 2 types of images were compared by paired rank-sum test. A P value <0.05 was considered statistically significant. Results: A total of 40 condyles from 20 patients were scanned. Among them, 8 condyles showed no bone changes, and the other 32 condyles demonstrated condylar osseous changes of varying degrees and nature. These 32 condyles were used in the subsequent analysis. As compared to images acquired by HNCC in the PDWI sequence, the WD-HNCC images more clearly showed mandibular osteophyte, bone cortical erosion, subcortical cystic focus, and bone cortical hyperplasia and thickening. In addition, the WD-HNCC was demonstrated to improve image CNR by 158.9% compared to HNCC (28.17±16.01 vs. 10.88±6.53; t=8.63; P=0.001). Conclusions: WD-HNCC in PDWI sequences is suitable for imaging the condylar bone changes of patients with TMD and significantly improves the image quality.

Magnetogenetic stimulation inside MRI induces spontaneous and evoked changes in neural circuits activity in rats.

The ability to modulate specific neural circuits and simultaneously visualize and measure brain activity with MRI would greatly impact understanding brain function in health and disease. The combination of neurostimulation methods and MRI in animal models have already shown promise in elucidating fundamental mechanisms associated with brain activity. We developed an innovative magnetogenetics neurostimulation technology that can trigger neural activity through magnetic fields. Similar to other genetic-based neuromodulation methods, magnetogenetics offers cell-, area- and temporal-specific control of neural activity. However, the magnetogenetics protein (Electromagnetic Preceptive Gene (EPG)) are activated by non-invasive magnetic fields, providing a unique way to target neural circuits by the MRI gradients while simultaneously measure their effect on brain activity. EPG was expressed in rat's visual cortex and the amplitude of low-frequency fluctuation (fALFF), resting-state functional connectivity (FC), and sensory activation was measured using a 7T MRI. The results demonstrate that EPG-expressing rats had significantly higher signal fluctuations in the visual areas and stronger FC in sensory areas consistent with known anatomical visuosensory and visuomotor connections. This new technology complements the existing neurostimulation toolbox and provides a mean to study brain function in a minimally-invasive way which was not possible previously.

Study on pharmacokinetics and tissue distribution of Polygonatum sibiricum polysaccharide in rats by fluorescence labeling.

To study the pharmacokinetics and tissue distribution characteristics of Polygonatum sibiricum (P. sibiricum) polysaccharide administered orally and intravenously in rats, the latest quantitative analysis method was established where P. sibiricum polysaccharide was labeled with fluorescein isothiocyanate (FITC) in plasma and tissues. Quantitative analysis method of P. sibiricum polysaccharide in rat plasma and tissues was established by fluorescence spectrophotometry with FITC as a highly sensitive fluorescent molecular probe. The results showed that P. sibiricum polysaccharide was successfully labeled with FITC, and the degree of substitution was 0.55 %. Pharmacokinetic characteristics showed that oral administration (ig) and intravenous injection (iv) were consistent with the characteristics of two-compartment model. PRP-TYR-FITC administered orally was poorly absorbed in rats with low bioavailability. After a single ig and iv administration in rats for 8 h, P. sibiricum polysaccharide can be distributed in most tissues. The analysis results showed that P. sibiricum polysaccharide was distributed mostly in lung, kidney and liver for both routes of administration. When taking orally, the distribution pattern was: lung > liver > kidney > small intestine > stomach > heart > spleen > brain. When taking intravenously, the distribution pattern was: liver > lung > kidney > small intestine > heart > stomach > spleen > brain. Fluorescence labeling of P. sibiricum polysaccharide by FITC was successfully realized. This method was proved to be suitable for the study of pharmacokinetics and tissue distribution of P. sibiricum polysaccharide in rats. The above research lays foundation for further elucidating the clinical pharmacological mechanism of polysaccharide in P. sibiricum.

Determination of polysaccharides composition in Polygonatum sibiricum and Polygonatum odoratum by HPLC-FLD with pre-column derivatization.

A high-performance liquid chromatography-fluorescence detection (HPLC-FLD) method was established for the determination of seven monosaccharides in Polygonatum sibiricum and Polygonatum odoratum. The polysaccharides were de-esterified, extracted, hydrolyzed and derivatized with p-aminobenzoic acid (PABA) to obtain fluorescently labeled monosaccharide compounds, which were finally detected by HPLC-FLD. Inertsil ODS-3, C18 chromatographic column (250 mm × 4.6 mm, 5 µm) was used for chromatography. The excitation wavelength (Ex) was 313 nm, and the emission wavelength (Em) was 358 nm. Ethyl acetate extraction reduced the peaks of chromatogram and improved the detection sensitivity than other agents. The established method had high sensitivity, strong specificity, good linear relationship and recovery efficiency. The results showed that the roots and fibrous roots of Polygonatum sibiricum and Polygonatum odoratum contained these seven monosaccharides, and the highest monosaccharide content was mannose. The method of PABA-HPLC-FLD for determination of monosaccharide content in Polygonatum sibiricum and Polygonatum odoratum was sensitive and accurate. The method established in this work provides a feasible analytical tool for the study of polysaccharides, and the findings on polysaccharides from Polygonatum sibiricum and Polygonatum odoratum can provide guidance for the natural medicine industry.

Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI.

Despite extensive studies detecting laminar functional magnetic resonance imaging (fMRI) signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across cortical regions remain to be fully investigated in both evoked and resting conditions at different brain states. Here, we developed a multislice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 µm) and temporal resolution (100 ms) in anesthetized rats. Across different trials, we detected either laminar-specific positive or negative blood-oxygen-level-dependent (BOLD) responses in the surrounding cortical region adjacent to the most activated cortex under the evoked condition. Specifically, in contrast to typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for trials with negative BOLD in adjacent regions, which indicated brain state-dependent laminar-fMRI responses based on corticocortical interaction. Also, in resting-state (rs-) fMRI study, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from caudal to rostral slices. In summary, our study provided a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity in evoked and resting-state MS-LS.

Focal fMRI signal enhancement with implantable inductively coupled detectors.

Despite extensive efforts to increase the signal-to-noise ratio (SNR) of fMRI images for brain-wide mapping, technical advances of focal brain signal enhancement are lacking, in particular, for animal brain imaging. Emerging studies have combined fMRI with fiber optic-based optogenetics to decipher circuit-specific neuromodulation from meso to macroscales. High-resolution fMRI is needed to integrate hemodynamic responses into cross-scale functional dynamics, but the SNR remains a limiting factor given the complex implantation setup of animal brains. Here, we developed a multimodal fMRI imaging platform with an implanted inductive coil detector. This detector boosts the tSNR of MRI images, showing a 2-3-fold sensitivity gain over conventional coil configuration. In contrast to the cryoprobe or array coils with limited spaces for implanted brain interface, this setup offers a unique advantage to study brain circuit connectivity with optogenetic stimulation and can be further extended to other multimodal fMRI mapping schemes.

Long-Range Detection of a Wirelessly Powered Resistive Transducer.

Wireless measurement of resistance variation is particularly desirable inside confined cavities where wire connection and battery replacement are undesirable. Compared to capacitive or inductive transducers, resistive transducers have better availability, whose resistance changes can be directly converted into detectable voltages by electric bridges. However, to wirelessly operate electric bridges on batteryless platforms, multistage circuits are required to convert dc signals into wireless signals, making the whole system hard to miniaturize without using complicated integrated circuits. Alternatively, resistive transducers can be incorporated into passive L C resonators for contactless characterization by the backscattering method. This design, however, is ineffective beyond the near field, and it requires complicated line shape analysis of resonators' frequency response curves. Here, we will significantly improve the remote detectability of a resistive transducer, by inductively coupling it with a parametric resonator. Upon activation by wireless pumping power with an external antenna, the parametric resonator can self-oscillate and emit strong oscillation signals. The temperature-induced resistance change is converted into linear frequency shifts of the oscillation signal that can be detected over large distance separations for up to 20-fold the sensor's own dimension. Every 0.1 °C of temperature change can be converted into 8 kHz of frequency shift that is approximately threefold larger than the linewidth of oscillation peak. This sensor maintains good linearity between 25 °C and 41 °C, providing enough range for physiological monitoring. In conclusion, we have fabricated a resistance-to-frequency converter for remote detection of resistance changes via a wirelessly powered parametric oscillator. Besides this proof-of-concept demonstration for temperature sensing, the general concept of resistance-to-frequency conversion will improve the remote detectability of a broad range of resistive transducers for physiological and environmental monitoring.

An Automatic Petechia Dots Detection Method on Tongue.

Tongue diagnosis with features like tongue coating, petechia, color, size and so on is of great effectiveness and convenience in traditional Chinese medicine. With the development of image processing techniques, automatic image processing can reduce hospital inspection for patients. However, there are ubiquitous problems of inadequate accuracy in petechia dots detection with previous methods. In this paper, we propose a method of petechia dots detection on tongue based on SimpleBlobDetector function in OpenCV library and support vector machines model, which improves the detective accuracy. We test 128 clinic tongue images and select 9 of the images with plentiful petechia dots for further experiments. Our method achieves mean value of false alarm rate 4.6% and missing alarm rate 11.8%, which have 19.4% and 8.2% reduction respectively compared to previous work.Clinical Relevance-The method can provide detailed information of tongue, which assists doctors to investigate curative effect.

Ginkgo Biloba Extract EGB761 Alleviates Warfarin-induced Aortic Valve Calcification Through the BMP2/Smad1/5/Runx2 Signaling Pathway.

ABSTRACT: Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.

Multi-session delivery of synchronous rTMS and sensory stimulation induces long-term plasticity.

BACKGROUND: Combining training or sensory stimulation with non-invasive brain stimulation has shown to improve performance in healthy subjects and improve brain function in patients after brain injury. However, the plasticity mechanisms and the optimal parameters to induce long-term and sustainable enhanced performance remain unknown. OBJECTIVE: This work was designed to identify the protocols of which combining sensory stimulation with repetitive transcranial magnetic stimulation (rTMS) will facilitate the greatest changes in fMRI activation maps in the rat's primary somatosensory cortex (S1). METHODS: Several protocols of combining forepaw electrical stimulation with rTMS were tested, including a single stimulation session compared to multiple, daily stimulation sessions, as well as synchronous and asynchronous delivery of both modalities. High-resolution fMRI was used to determine how pairing sensory stimulation with rTMS induced short and long-term plasticity in the rat S1. RESULTS: All groups that received a single session of rTMS showed short-term increases in S1 activity, but these increases did not last three days after the session. The group that received a stimulation protocol of 10 Hz forepaw stimulation that was delivered simultaneously with 10 Hz rTMS for five consecutive days demonstrated the greatest increases in the extent of the evoked fMRI responses compared to groups that received other stimulation protocols. CONCLUSIONS: Our results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. These results will be important to lead the design of new training and rehabilitation paradigms and training towards achieving maximal performance in healthy subjects.

Simultaneous Determination of Six Alkaloids in Rat Plasma by SPE-HPLC-MS/MS and Their Pharmacokinetics after Oral Administration of Radix aconiti Preparata Extract.

Simultaneous determination of the content of six alkaloids (aconitine, hypoaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, and benzoylmesaconine) in rat plasma is enabled by HPLC-MS/MS combined with microsolid phase extraction (micro-SPE). To study its pharmacokinetics in rat plasma, the extracted plasma sample was passed through a C18 extraction column and eluted with acetonitrile. The six alkaloids in the Radix aconiti Preparata extract can be completely separated as peaks with good shape. The six components in the plasma sample showed a good linear relationship within their respective linear ranges (R 2 > 0.997). The analysis of the six alkaloids can be completed within 20 min. This method has high intraday and interday precision, and the room temperature stability and freeze-thaw stability are good. The matrix effect of the plasma samples is between 86.4 and 114%. The metabolism of the six Aconitum alkaloids in plasma is analyzed using a two-compartment model, which is characterized by fast absorption, slow elimination, and good linear fit, R 2 > 0.99. The peak time (T max) for aconitine, hypaconitine, and neoaconitine ranged from 29.95 to 42.07 min, while the peak time (T max) for benzoaconitine, benzohypaconitine, and benzoxinaconitine ranged from 42.88 to 73.08 min. With the increased dosage, the bioavailability of Aconitum alkaloids decreased gradually. The method for the determination of Aconitum alkaloids in rat plasma by high performance liquid chromatography-tandem mass spectrometry is sensitive and accurate, which is suitable for rat plasma analysis. The results provide a scientific basis for metabolic study of Aconitum alkaloids in vivo, and pave the way for clinical use of Aconitum medicinal materials and extracts.

Non-invasive neuromodulation using rTMS and the electromagnetic-perceptive gene (EPG) facilitates plasticity after nerve injury.

BACKGROUND: Twenty million Americans suffer from peripheral nerve injury. These patients often develop chronic pain and sensory dysfunctions. In the past decade, neuroimaging studies showed that these changes are associated with altered cortical excitation-inhibition balance and maladaptive plasticity. We tested if neuromodulation of the deprived sensory cortex could restore the cortical balance, and whether it would be effective in alleviating sensory complications. OBJECTIVE: We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which induces neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from glass catfish and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. METHODS: A rat model of forepaw denervation was used. rTMS was delivered every other day for 30 days, starting at the acute or at the chronic post-injury phase. A minimally-invasive neuromodulation via EPG was performed every day for 30 days starting at the chronic phase. A battery of behavioral tests was performed in the days and weeks following limb denervation in EPG-treated rats, and behavioral tests, fMRI and immunochemistry were performed in rTMS-treated rats. RESULTS: The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The results identify that both acute and delayed rTMS intervention facilitated rehabilitation. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. CONCLUSION: Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.