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Browsing by Author "Jin, Xiaoming"
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Item 4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation(Cambridge University Press, 2020-07-29) Nguyen, Tyler; Vriesman, Zoe; Andrews, Peter; Masood, Sehban; Stewart, M.; Khizroev, Sakhrat; Jin, Xiaoming; Anesthesia, School of MedicineOBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.Item Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial(Elsevier, 2022-02-12) Bao, Chunhui; Wu, Luyi; Wang, Di; Chen, Liming; Jin, Xiaoming; Shi, Yin; Li, Guona; Zhang, Jingzhi; Zeng, Xiaoqing; Chen, Jianhua; Liu, Huirong; Wu, Huangan; Anatomy, Cell Biology and Physiology, School of MedicineBackground: The efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients. Methods: This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037. Findings: At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture. Interpretation: Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines.Item Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial(BMJ, 2016) Chen, Lifang; Fang, Jianqiao; Jin, Xiaoming; Keeler, Crystal Lynn; Gao, Hong; Fang, Zhen; Chen, Qin; Department of Anatomy and Cell Biology, IU School of MedicineINTRODUCTION: Stroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors are the main cause of young ischaemic stroke. Acupuncture has been shown to benefit stroke rehabilitation and ameliorate the risk factors for stroke. The aims of this study were to determine whether acupuncture treatment will be effective in improving the activities of daily living (ADL), motor function and quality of life (QOL) in patients of young ischaemic stroke, and in preventing stroke recurrence by controlling blood pressure, lipids and body weight. METHODS AND ANALYSIS: In this randomised, sham-controlled, participant-blinded and assessor-blinded clinical trial, 120 patients between 18 and 45 years of age with a recent (within 1 month) ischaemic stroke will be randomised for an 8-week acupuncture or sham acupuncture treatment. The primary outcome will be the Barthel Index for ADL. The secondary outcomes will include the Fugl-Meyer Assessment for motor function; the World Health Organization Quality of Life BREF (WHOQOL-BREF) for QOL; and risk factors that are measured by ambulatory blood pressure, the fasting serum lipid, body mass index and waist circumference. Incidence of adverse events and long-term mortality and recurrence rate during a 10-year and 30-year follow-up will also be investigated. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Protocol V.3 was approved in June 2013. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone during follow-up calls enquiring on the patient's post-study health status. TRIAL REGISTRATION NUMBER: ChiCTR-TRC- 13003317; Pre-results.Item Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice(Wiley, 2021) Ping, Xingjie; Chai, Zhi; Wang, Weiping; Ma, Cungen; White, Fletcher A.; Jin, Xiaoming; Anatomy, Cell Biology and Physiology, School of MedicineObjective: Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis. Methods: In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology. Results: Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAb- or TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation. Significance: RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.Item Characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and GDNF treatment(Elsevier, 2016-03) Deng, Lingxiao; Ruan, Yiwen; Chen, Chen; Frye, Christian Corbin; Xiong, Wenhui; Jin, Xiaoming; Jones, Kathryn; Sengelaub, Dale; Xu, Xiao-Ming; Department of Anatomy & Cell Biology, IU School of MedicineAfter spinal cord injury (SCI), poor regeneration of damaged axons of the central nervous system (CNS) causes limited functional recovery. This limited spontaneous functional recovery has been attributed, to a large extent, to the plasticity of propriospinal neurons, especially the descending propriospinal neurons (dPSNs). Compared with the supraspinal counterparts, dPSNs have displayed significantly greater regenerative capacity, which can be further enhanced by glial cell line-derived neurotrophic factor (GDNF). In the present study, we applied a G-mutated rabies virus (G-Rabies) co-expressing green fluorescence protein (GFP) to reveal Golgi-like dendritic morphology of dPSNs. We also investigated the neurotransmitters expressed by dPSNs after labeling with a retrograde tracer Fluoro-Gold (FG). dPSNs were examined in animals with sham injuries or complete spinal transections with or without GDNF treatment. Bilateral injections of G-Rabies and FG were made into the 2nd lumbar (L2) spinal cord at 3 days prior to a spinal cord transection performed at the 11th thoracic level (T11). The lesion gap was filled with Gelfoam containing either saline or GDNF in the injury groups. Four days post-injury, the rats were sacrificed for analysis. For those animals receiving G-rabies injection, the GFP signal in the T7-9 spinal cord was visualized via 2-photon microscopy. Dendritic morphology from stack images was traced and analyzed using a Neurolucida software. We found that dPSNs in sham injured animals had a predominantly dorsal-ventral distribution of dendrites. Transection injury resulted in alterations in the dendritic distribution with dorsal-ventral retraction and lateral-medial extension. Treatment with GDNF significantly increased the terminal dendritic length of dPSNs. The density of spine-like structures was increased after injury, and treatment with GDNF enhanced this effect. For the group receiving FG injections, immunohistochemistry for glutamate, choline acetyltransferase (ChAT), glycine, and GABA was performed in the T7-9 spinal cord. We show that the majority of FG retrogradely-labeled dPSNs were located in the Rexed Lamina VII. Over 90% of FG-labeled neurons were glutamatergic, with the other three neurotransmitters contributing less than 10% of the total. To our knowledge this is the first report describing the morphologic characteristics of dPSNs and their neurotransmitter expressions, as well as the dendritic response of dPSNs after transection injury and GDNF treatment.Item Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice(Public Library of Science (PLoS), 2016) Ping, Xingjie; Jin, Xiaoming; Department of Anatomy & Cell Biology, IU School of MedicinePosttraumatic epilepsy (PTE) usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG) in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16-50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ) test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.Item Cortical stimulation for treatment of neurological disorders of hyperexcitability: a role of homeostatic plasticity(Wolters Kluwer, 2019-01) Chai, Zhi; Ma, Cungen; Jin, Xiaoming; Anatomy and Cell Biology, IU School of MedicineHyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.Item Difference in regional neural fluctuations and functional connectivity in Crohn’s disease: a resting-state functional MRI study(Springer, 2018) Bao, Chunhui; Liu, Peng; Liu, Huirong; Jin, Xiaoming; Shi, Yin; Wu, Luyi; Zeng, Xiaoqing; Zhang, Jianye; Wang, Di; Calhoun, Vince D.; Tian, Jie; Wu, Huangan; Anatomy and Cell Biology, School of MedicinePatients with Crohn’s disease (CD) are shown to have abnormal changes in brain structures. This study aimed to further investigate whether these patients have abnormal brain activities and network connectivity. Sixty patients with CD and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were used to assess differences in spontaneous regional brain activity and functional connectivity. Compared to the HCs, patients with CD showed significantly higher ALFF values in hippocampus and parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior frontal cortex and precuneus. The ALFF values were significantly lower in secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal cortex. Functional connectivities between left HIPP and left inferior temporal cortex, and right middle cingulate cortex, HIPP, and fusiform area were significantly lower. The functional connectivities between right HIPP and right inferior orbitofrontal cortex and left HIPP were also significantly lower. Patients with CD showed higher or lower spontaneous activity in multiple brain regions. Altered activities in these brain regions may collectively reflect abnormal function and regulation of visceral pain and sensation, external environmental monitoring, and cognitive processing in these patients. Lower functional connectivity of the hippocampus-limbic system was observed in these patients. These findings may provide more information to elucidate the neurobiological mechanisms of the disease.Item Differences in brain gray matter volume in patients with Crohn’s disease with and without abdominal pain(Impact Journals, 2017-09-22) Bao, Chunhui; Liu, Peng; Shi, Yin; Wu, Luyi; Jin, Xiaoming; Zeng, Xiaoqing; Zhang, Jianye; Wang, Di; Liu, Huirong; Wu, Huangan; Anatomy and Cell Biology, School of MedicineIncreasing evidence indicates that abnormal pain processing is present in the central nervous system of patients with Crohn’s disease (CD). The purposes of this study were to assess changes in gray matter (GM) volumes in CD patients in remission and to correlate structural changes in the brain with abdominal pain. We used a 3.0 T magnetic resonance scanner to examine the GM structures in 21 CD patients with abdominal pain, 26 CD patients without abdominal pain, and 30 healthy control subjects (HCs). Voxel-based morphometric analyses were used to assess the brain GM volumes. Patients with abdominal pain exhibited higher CD activity index and lower inflammatory bowel disease questionnaire scores than those of the patients without abdominal pain. Compare to HCs and to patients without abdominal pain, patients with abdominal pain exhibited lower GM volumes in the insula and anterior cingulate cortex (ACC); whereas compare to HCs and to patients with abdominal pain, the patients without abdominal pain exhibited higher GM volumes in the hippocampal and parahippocampal cortex. The GM volumes in the insula and ACC were significantly negatively correlated with daily pain scores. These results suggest that differences exist in the brain GM volume between CD patients in remission with and without abdominal pain. The negative correlation between the GM volumes in the insula and ACC and the presence and severity of abdominal pain in CD suggests these structures are closely related to visceral pain processing.Item Different brain responses to electro-acupuncture and moxibustion treatment in patients with Crohn's disease(Nature Publishing Group, 2016-11-18) Bao, Chunhui; Liu, Peng; Liu, Huirong; Jin, Xiaoming; Calhoun, Vince D.; Wu, Luyi; Shi, Yin; Zhang, Jianye; Zeng, Xiaoqing; Ma, Lili; Qin, Wei; Zhang, Jingzhi; Liu, Xiaoming; Tian, Jie; Wu, Huangan; Department of Anatomy and Cell Biology, School of MedicineThis study aimed to investigate changes in resting state brain activity in remissive Crohn's Disease (CD) patients after electro-acupuncture or moxibustion treatment. Fifty-two CD patients and 36 healthy subjects were enrolled, and 36 patients were equally and randomly assigned to receive either electro-acupuncture or moxibustion treatment for twelve weeks. We used resting state functional magnetic resonance imaging to assess Regional Homogeneity (ReHo) levels, and Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ) scores to evaluate disease severity and quality of life. The results show that (i) The ReHo levels in CD patients were significantly increased in cortical but decreased in subcortical areas, and the coupling between them was declined. (ii) Both treatments decreased CDAI, increased IBDQ scores, and normalized the ReHo values of the cortical and subcortical regions. (iii) ReHo changes in multiple cortical regions were significantly correlated with CDAI score decreases. ReHo changes in several subcortical regions in the electro-acupuncture group, and those of several cortical regions in the moxibustion group, were correlated with reduced CDAI. These findings suggest that both treatments improved cortex-subcortical coupling in remissive CD patients, but electro-acupuncture regulated homeostatic afferent processing network, while moxibustion mainly regulated the default mode network of the brain.