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1.
iScience ; 26(6): 106784, 2023 Jun 16.
Article En | MEDLINE | ID: mdl-37378337

Graph theory-based analysis describes the brain as a complex network. Only a few studies have examined modular composition and functional connectivity (FC) between modules in patients with spinal cord injury (SCI). Little is known about the longitudinal changes in hubs and topological properties at the modular level after SCI and treatment. We analyzed differences in FC and nodal metrics reflecting modular interaction to investigate brain reorganization after SCI-induced compensation and neurotrophin-3 (NT3)-chitosan-induced regeneration. Mean inter-modular FC and participation coefficient of areas related to motor coordination were significantly higher in the treatment animals than in the SCI-only ones at the late stage. The magnocellular part of the red nucleus may reflect the best difference in brain reorganization after SCI and therapy. Treatment can enhance information flows between regions and promote the integration of motor functions to return to normal. These findings may reveal the information processing of disrupted network modules.

2.
Sheng Li Xue Bao ; 75(2): 231-240, 2023 Apr 25.
Article Zh | MEDLINE | ID: mdl-37089097

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.


Brain Hemorrhage, Traumatic , Brain , Ischemic Stroke , Neurogenesis , Adult , Animals , Humans , Brain/physiology , Brain/physiopathology , Hippocampus/physiology , Hippocampus/physiopathology , Mammals/physiology , Neurogenesis/physiology , Brain Hemorrhage, Traumatic/physiopathology , Brain Hemorrhage, Traumatic/therapy , Ischemic Stroke/physiopathology , Ischemic Stroke/therapy , Recovery of Function , Spinal Cord/physiology , Spinal Cord/physiopathology
3.
Comput Methods Programs Biomed ; 228: 107252, 2023 Jan.
Article En | MEDLINE | ID: mdl-36434959

BACKGROUND AND OBJECTIVE: The cystic cavity and its surrounding dense glial scar formed in chronic spinal cord injury (SCI) hinder the regeneration of nerve axons. Accurate location of the necrotic regions formed by the scar and the cavity is conducive to eliminate the re-growth obstacles and promote SCI treatment. This work aims to realize the accurate and automatic location of necrotic regions in the chronic SCI magnetic resonance imaging (MRI). METHODS: In this study, a method based on superpixel is proposed to identify the necrotic regions of spinal cord in chronic SCI MRI. Superpixels were obtained by a simple linear iterative clustering algorithm, and feature sets were constructed from intensity statistical features, gray level co-occurrence matrix features, Gabor texture features, local binary pattern features and superpixel areas. Subsequently, the recognition effects of support vector machine (SVM) and random forest (RF) classification model on necrotic regions were compared from accuracy (ACC), positive predictive value (PPV), sensitivity (SE), specificity (SP), Dice coefficient and algorithm running time. RESULTS: The method is evaluated on T1- and T2-weighted MRI spinal cord images of 24 adult female Wistar rats. And an automatic recognition method for spinal cord necrosis regions was established based on the SVM classification model finally. The recognition results were 1.00±0.00 (ACC), 0.89±0.09 (PPV), 0.88±0.12 (SE), 1.00±0.00 (SP) and 0.88±0.07 (Dice), respectively. CONCLUSIONS: The proposed method can accurately and noninvasively identify the necrotic regions in MRI, which is helpful for the pre-intervention assessment and post-intervention evaluation of chronic SCI research and treatments, and promoting the clinical transformation of chronic SCI research.


Magnetic Resonance Imaging , Spinal Cord Injuries , Female , Rats , Animals , Rats, Wistar , Spinal Cord Injuries/diagnostic imaging , Necrosis
4.
Front Immunol ; 13: 1052542, 2022.
Article En | MEDLINE | ID: mdl-36466925

Background: Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Methods: Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. Results: After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). Conclusion: For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.


Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/therapy , Neoadjuvant Therapy , Esophageal Neoplasms/therapy , Immunotherapy/adverse effects , Postoperative Complications , Treatment Outcome
5.
Ann Med ; 54(1): 1867-1883, 2022 12.
Article En | MEDLINE | ID: mdl-35792748

PURPOSE: Spinal cord injury (SCI) destroys the sensorimotor pathway and induces brain plasticity. However, the effect of treatment-induced spinal cord tissue regeneration on brain functional reorganization remains unclear. This study was designed to investigate the large-scale functional interactions in the brains of adult female Rhesus monkeys with injured and regenerated thoracic spinal cord. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) combined with Granger Causality analysis (GCA) and motor behaviour analysis were used to assess the causal interaction between sensorimotor cortices, and calculate the relationship between causal interaction and hindlimb stepping in nine Rhesus monkeys undergoing lesion-induced spontaneous recovery (injured, n = 4) and neurotrophin-3/chitosan transplantation-induced regeneration (NT3-chitosan, n = 5) after SCI. RESULTS: The results showed that the injured and NT3-chitosan-treated animals had distinct spatiotemporal features of brain functional reorganization. The spontaneous recovery followed the model of "early intra-hemispheric reorganization dominant, late inter-hemispheric reorganization dominant", whereas regenerative therapy animals showed the opposite trend. Although the variation degree of information flow intensity was consistent, the tendency and the relationship between local neuronal activity properties and coupling strength were different between the two groups. In addition, the injured and NT3-chitosan-treated animals had similar motor adjustments but various relationship modes between motor performance and information flow intensity. CONCLUSIONS: Our findings show that brain functional reorganization induced by regeneration therapy differed from spontaneous recovery after SCI. The influence of unique changes in brain plasticity on the therapeutic effects of future regeneration therapy strategies should be considered. Key messagesNeural regeneration elicited a unique spatiotemporal mode of brain functional reorganization in the spinal cord injured monkeys, and that regeneration does not simply reverse the process of brain plasticity induced by spinal cord injury (SCI).Independent "properties of local activity - intensity of information flow" relationships between the injured and treated animals indicating that spontaneous recovery and regenerative therapy exerted different effects on the reorganization of the motor network after SCI.A specific information flow from the left thalamus to the right insular can serve as an indicator to reflect a heterogeneous "information flow - motor performance" relationship between injured and treated animals at similar motor adjustments.


Chitosan , Spinal Cord Injuries , Animals , Brain , Female , Humans , Macaca mulatta , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(5): 485-490, 2022 Sep.
Article Zh | MEDLINE | ID: mdl-37088757

OBJECTIVE: To investigate the electrophysiological properties of pyramidal neurons in mouse motor cortex during the early postnatal development. METHODS: Thirty-six mice were randomly divided into postnatal 1-, 2-, 3-Week and 1-, 2-,3-Month groups (n=6). Membrane properties, action potentials (AP) and spontaneous excitatory postsynaptic currents (sEPSCs) of motor cortex pyramidal neurons were recorded to evaluate the changes in the intrinsic electrophysilogical characteristics by using whole cell patch clamp. Pyramidal neurons and interneurons were distinguished according to the AP firing patterns. RESULTS: Comparing with interneurons, pyramidal neurons exhibited regular spiking (RS) with smaller frequency. During the period of postnatal 1 Week-3 Months, some of the intrinsic membrane properties of motor cortex pyramidal neurons changed. Compared to the 1-Week mice, the resting membrane potential (RMP) of 2-Week decreased significantly (P<0.01), and the membrane input resistance (Rin) of 1-Month got a hyperpolarization (P<0.01), and they showed no significant change in the next period, while the membrane capacitance (Cm) showed no significant changes during the whole postnatal development. The AP dynamic properties changed significantly during this period. Compared to the 1-Week mice, the absolute value of the AP threshold and the AP amplitude of the 3-Week increased significantly (P<0.01), while the spike half width of the 2-Week decreased substantially (P<0.05), and they showed no significant change in the next period. The sEPSCs frequency and amplitude of 1- Month increased significantly compared to the 1-Week mice(P<0.01), while during the period of next 1 Month-3 Months, the amplitude and frequency showed no significant change. CONCLUSION: These results suggest that the motor cortex pyramidal neurons have time-specific eletrophysilogical properties during the postnatal development. The electrophysiological properties can be used as a functional index to detect the degree of neurons maturity, and as a marker to distinguish the pyramidal neurons and interneurons.


Motor Cortex , Animals , Mice , Pyramidal Cells/physiology , Action Potentials/physiology
7.
Neural Regen Res ; 17(5): 1146-1155, 2022 May.
Article En | MEDLINE | ID: mdl-34558544

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length, it still has some shortcomings, such as insufficient donors and secondary injury. Composite chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve defects. However, the effects on extended nerve defects remain poorly understood. In this study, we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment (20 mm) sciatic nerve defects in adult rats. The results showed that treatment markedly promoted the recovery of motor and sensory functions. The regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also reconstructed. In addition, the regenerated sciatic nerve reconnected the motor endplate with the target muscle. Therefore, this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional circuits. This provides a promising method for the clinical treatment of extended peripheral nerve injury. This study was approved by the Animal Ethics Committee of Capital Medical University, China (approval No. AEEI-2017-033) on March 21, 2017.

8.
Sheng Li Xue Bao ; 74(6): 1039-1047, 2022 Dec 25.
Article Zh | MEDLINE | ID: mdl-36594392

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.


Muscle Spindles , Muscle, Skeletal , Muscle Spindles/anatomy & histology , Muscle Spindles/physiology , Muscle, Skeletal/physiology , Clinical Relevance
9.
Article En | MEDLINE | ID: mdl-31871480

OBJECTIVE: The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center. METHODS: Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group (n = 62) and the control group (n = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention. RESULTS: After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly (P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly (P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant (P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively). CONCLUSION: A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period.

10.
J Med Primatol ; 48(6): 320-328, 2019 12.
Article En | MEDLINE | ID: mdl-31148186

BACKGROUND: The relatively tiny spinal cord of non-human primate (NHP) causes increased challenge in diffusion tensor imaging (DTI) post-processing. This study aimed to establish a reliable correction strategy applied to clinical DTI images of NHP. METHODS: Six normal and partial spinal cord injury (SCI) rhesus monkeys underwent 3T MR scanning. A correction strategy combining multiple iterations and non-rigid deformation was used for DTI image post-processing. Quantitative evaluations were then conducted to investigate effects of distortion correction. RESULTS: After correction, longitudinal geometric distortion, global distortion, and residual distance errors were all significantly decreased (P < 0.05). Fractional anisotropy at the injured site was remarkably lower than that at the contralateral site (P = 0.0488) and was substantially lower than those at the adjacent superior (P = 0.0157) and inferior (P = 0.0128) areas at the same side. CONCLUSIONS: Our image correction strategy can improve the quality of the DTI images of NHP thoracic cords, contributing to the development of SCI preclinical research.


Diffusion Tensor Imaging/veterinary , Macaca mulatta/anatomy & histology , Spinal Cord Injuries/veterinary , Spinal Cord/diagnostic imaging , Animals , Artifacts , Female , Spinal Cord Injuries/diagnostic imaging
11.
Exp Anim ; 68(3): 341-349, 2019 Aug 14.
Article En | MEDLINE | ID: mdl-30930341

Walking is characterized by repetitive limb movements associated with highly structured patterns of muscle activity. The causal relationships between the muscle activities and hindlimb segments of walking are difficult to decipher. This study investigated these particular relationships and clarified whether they are correlated with speed to further understand the neuromuscular control pattern. Four adult female rhesus monkeys (Macaca mulatta) were selected to record gait parameters while walking on a bipedal treadmill at speeds of 0.2, 0.8, 1.4, and 2.0 km/h. We recorded 3 ipsilateral hindlimb muscles by surface recording. In this study, we calculated the correlations between electromyography (EMG) and kinematic parameters (24 EMG*17 kinematic parameters). Of the 408 calculated coefficients, 71.6% showed significant linear correlations. Significant linear correlations were found between muscle activity, such as burst amplitudes and the integral of muscle activity, and the corresponding kinematic parameters of each joint. Most of these relationships were speed independent (91.7% of all variables). Through correlation analysis, this study demonstrated a causal association between kinematic and EMG patterns of rhesus monkey locomotion. Individuals have particular musculoskeletal control patterns, and most of the relationships between hindlimb segments and muscles are speed independent. The current findings may enhance our understanding of neuromusculoskeletal control strategies.


Macaca mulatta/physiology , Muscle, Skeletal/physiology , Walking/physiology , Animals , Biomechanical Phenomena , Electromyography , Female
12.
Exp Anim ; 67(4): 431-440, 2018 Nov 01.
Article En | MEDLINE | ID: mdl-29769463

After incomplete spinal cord injury (SCI), neural circuits may be plastically reconstructed to some degree, resulting in extensive functional locomotor recovery. The present study aimed to observe the post-SCI locomotor recovery of rhesus monkey hindlimbs and compare the recovery degrees of different hindlimb parts, thus revealing the recovery process of locomotor function. Four rhesus monkeys were chosen for thoracic hemisection injury. The hindlimb locomotor performance of these animals was recorded before surgery, as well as 6 and 12 weeks post-lesion. Via principal component analysis, the relevant parameters of the limb endpoint, pelvis, hindlimb segments, and joints were processed and analyzed. Twelve weeks after surgery, partial kinematic recovery was observed at the limb endpoint, shank, foot, and knee joints, and the locomotor performance of the ankle joint even recovered to the pre-lesion level; the elevation angle of the thigh and hip joints showed no obvious recovery. Generally, different parts of a monkey hindlimb had different spontaneous recovery processes; specifically, the closer the part was to the distal end, the more extensive was the locomotor function recovery. Therefore, we speculate that locomotor recovery may be attributed to plastic reconstruction of the motor circuits that are mainly composed of corticospinal tract. This would help to further understand the plasticity of motor circuits after spinal cord injury.


Hindlimb/physiopathology , Motor Activity , Nerve Regeneration/physiology , Recovery of Function/physiology , Spinal Cord Injuries/physiopathology , Animals , Biomechanical Phenomena , Female , Macaca mulatta , Neuronal Plasticity/physiology , Pyramidal Tracts/physiopathology
13.
Sheng Li Xue Bao ; 70(2): 106-114, 2018 Apr 25.
Article Zh | MEDLINE | ID: mdl-29691574

The present study was aimed to investigate the electrophysiological characteristics of hippocampal postnatal early development mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rats. Forty-eight Wistar rats were divided into postnatal 0.5-, 1-, 2- and 3-month groups (n = 12). Spontaneous excitatory postsynaptic currents (sEPSCs) and field excitatory postsynaptic potentials (fEPSPs) mediated by AMPA receptors were recorded to evaluate the changes in the intrinsic membrane properties of hippocampal CA1 pyramidal neurons by using patch-clamp and MED64 planar microelectrode array technique respectively. The results showed that, during the period of postnatal 0.5-3 months, some of the intrinsic membrane properties of hippocampal CA1 pyramidal neurons, such as the membrane capacitance (Cm) and the resting membrane potential (RMP), showed no significant changes, while the membrane input resistance (Rin) and the time constant (τ) of the cells were decreased significantly. The amplitude, frequency and kinetics (both rise and decay times) of sEPSCs were significantly increased during the period of postnatal 0.5-1 month, but they were all decreased during the period of postnatal 1-3 months. In addition, the range of evoked fEPSPs in hippocamal CA1 region was significantly expanded, but the fEPSP amplitudes were decreased significantly during the period of postnatal 0.5-3 months. Furthermore, the evoked fEPSPs could be significantly inhibited by extracellular application of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These results suggest that AMPA receptor may act as a major type of excitatory receptor to regulate synaptic transmission and connections during the early stage of hippocampal postnatal development, which promotes the development and functional maturation of hippocampus in rats.


CA1 Region, Hippocampal/physiology , Excitatory Postsynaptic Potentials , Pyramidal Cells/physiology , Receptors, AMPA/physiology , Animals , Rats , Rats, Wistar , Synaptic Transmission
14.
Magn Reson Imaging ; 47: 25-32, 2018 04.
Article En | MEDLINE | ID: mdl-29154896

PURPOSE: Adequate evaluation of spinal cord parenchyma and accurate identification of injury range are considered two premises for the research and treatment of chronic spinal cord injury (SCI). Diffusion tensor imaging (DTI) provides information about water diffusion in spinal cord, and thus makes it possible to realize these premises. METHOD: In this study, we conducted magnetic resonance imaging (MRI) for Wistar rats 84days after spinal cord contusion. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) from different positions of the injured cord were collected, analyzed, and compared with the histological results and locomotor outcomes. Moreover, we performed fiber tractography, and examined the difference in cavity percentage obtained respectively via conventional MRI, DTI and histology. RESULTS: Results showed that the chronic SCI rats had the largest changes of all DTI metrics at the epicenter; the farther away from the epicenter, the smaller the variation. FA, AD and RD were all influenced by SCI in a greater space range than MD. The good consistency of FA values and histological results in specific regions evidenced FA's capability of reflecting Wallerian degeneration after SCI. DTI metrics at the epicenter in ventral funiculus also showed a close correlation with the BBB scores. Additionally, supported by the histological results, DTI enables a more accurate measurement of cavity percentage compared to the conventional MRI. CONCLUSION: DTI parameters might comprehensively reflect the post-SCI pathological status of spinal cord parenchyma at the epicenter and distal parts during the chronic stage, while showing good consistency with locomotor performance. DTI combined with tractography could intuitively display the distribution of spared fibers after SCI and accurately provide information such as cavity area. This may shed light on the research and treatment of chronic SCI.


Diffusion Tensor Imaging , Spinal Cord Injuries/diagnostic imaging , Spinal Cord/diagnostic imaging , White Matter/diagnostic imaging , Animals , Anisotropy , Biomarkers/metabolism , Blood-Brain Barrier , Female , Magnetic Resonance Imaging , Rats , Rats, Wistar , Spinal Cord/pathology , Spinal Cord Injuries/pathology , White Matter/pathology
15.
Neuroradiology ; 59(12): 1203-1212, 2017 Dec.
Article En | MEDLINE | ID: mdl-28856389

PURPOSE: The understanding of microstructural and metabolic changes in the post-traumatic brain injury is the key to brain damage suppression and repair in clinics. METHODS: Ten female Wistar rats were traumatically injured in the brain CA1 region and above the cortex. Next, diffusion tensor magnetic resonance imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) were used to analyze the microstructural and metabolic changes in the brain within the following 2 weeks. RESULTS: Anisotropy fraction (FA) and axial diffusivity (AD) of the corpus callosum (CC) began to decrease significantly at day 1, whereas radial diffusivity (RD) significantly increased immediately after injury, reflecting the loss of white matter integrity. Compared with day 3, RD decreased significantly at day 7, implicating the angioedema reduction. In the hippocampus, FA significantly increased at day 7; the choline-containing compounds (Cho) and myo-inositol (MI) remarkably increased at day 7 compared with those at day 3, indicating the proliferation of astrocytes and radial glial cells after day 7. No significant differences between DTI and 1H MRS parameters were observed between day 1 and day 3. CONCLUSION: Day 1-3 after traumatic brain injury (TBI) may serve as a relatively appropriate time window for treatment planning and the following nerve repair.


Brain Injuries/diagnostic imaging , Proton Magnetic Resonance Spectroscopy/methods , Animals , Anisotropy , Brain Chemistry , Brain Injuries/metabolism , Brain Injuries/pathology , Diffusion Tensor Imaging/methods , Female , Rats , Rats, Wistar
16.
Magn Reson Imaging ; 43: 144-150, 2017 11.
Article En | MEDLINE | ID: mdl-28755862

OBJECTIVE: Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. METHODS: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. RESULTS: Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). CONCLUSIONS: These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status.


Brain Mapping , Brain/diagnostic imaging , Ketamine/pharmacology , Anesthesia , Anesthetics, Dissociative/pharmacology , Animals , Brain/physiopathology , Caudate Nucleus/diagnostic imaging , Cognition Disorders/diagnostic imaging , Female , Heart Rate/drug effects , Hippocampus/diagnostic imaging , Macaca mulatta , Magnetic Resonance Imaging , Prefrontal Cortex/diagnostic imaging , Putamen/diagnostic imaging , Respiration/drug effects , Rest
17.
J Med Primatol ; 46(5): 239-247, 2017 10.
Article En | MEDLINE | ID: mdl-28543057

BACKGROUND: Spinal cord injury (SCI) causes loss of locomotor functions. Nowadays, the relationship between the residual locomotion after SCI and the diffusion tensor tractography (DTT) results still remains unclear. METHODS: Four rhesus monkeys were suffered thoracic cord hemisection. Kinematic evaluation and DTT were performed prior- and post-SCI (6 and 12 weeks). The longitudinal changes of gait parameters and the DTT parameters were analyzed for the injury-contralateral hindlimb. The correlations between gaits and DTT parameters were also investigated. RESULTS: Almost gait parameters significantly changed after SCI, meanwhile, the caudal-rostral connection rate of DTT showed negative correlation with all gait parameters, demonstrating that the locomotor changes of the injury-contralateral hindlimb were associated with the ratio of residual fibers. CONCLUSIONS: The combinatory use of gait analysis and DTT has been demonstrated to be sensitive to locomotion changes after SCI, and may therefore have potential applications in the pre-clinical studies of SCI.


Gait , Leg/physiopathology , Macaca mulatta/injuries , Macaca mulatta/physiology , Motor Activity , Recovery of Function , Spinal Cord Injuries/physiopathology , Animals , Biomechanical Phenomena , Diffusion Tensor Imaging , Disease Models, Animal , Female , Reproducibility of Results , Sensitivity and Specificity , Spinal Cord Injuries/diagnostic imaging
18.
Cancer Biomark ; 18(1): 95-104, 2017.
Article En | MEDLINE | ID: mdl-27983539

Our study aimed to explore the effects of long noncoding RNA (lncRNA)-ANCR on the invasion and migration of colorectal cancer (CRC) cells by regulating enhancer of zeste homolog 2 (EZH2) expression. CRC tissues and adjacent normal tissues were collected and CRC SW620 cells line and normal human intestinal epithelial cells (HIECs) were incubated. CRC SW620 cells line was transfected with ANCR-siRNA. The expressions of ANCR and EZH2 mRNA were measured by real-time quantitative polymerase chain reaction (RT-qPCR). EZH2 and trimethylation of H3K27 (H3K27me3) protein expressions were detected using Western blotting. The relationship between ANCR and EZH2 was determined through RNA pull-down and co-immunoprecipitation (co-IP) assays. Cell invasion and migration were determined by Trans-well and cell scratch assays. ANCR, EZH2 and H3K27me3 expressions were up-regulated in CRC tissues and SW620 cells (all P < 0.05). After transfected with ANCR-siRNA, SW620 cells showed decreased ANCR expression and EZH2 mRNA and protein expressions (all P < 0.05). According to the results of RNA pull-down and co-IP assays, ANCR could specifically bind to EZH2. The results of Trans-well and cell scratch tests showed that when ANCR expression was decreased, the invasion and migration abilities of SW620 cells significantly declined (both P < 0.05). In conclusion, these results suggest that lncRNA-ANCR could influence the invasion and migration of CRC cells by specifically binding to EZH2.


Cell Movement/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Enhancer of Zeste Homolog 2 Protein/genetics , RNA, Long Noncoding/genetics , Cell Line, Tumor , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Invasiveness , RNA, Long Noncoding/biosynthesis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics
19.
J Med Primatol ; 45(6): 304-311, 2016 12.
Article En | MEDLINE | ID: mdl-27640786

BACKGROUND: The primate model of bipedal locomotion has been extensively used to study human evolution and played a critical role in exploring the pathological mechanisms of human neurologic disease and spinal cord injury. Speed has great influence on both walking posture and gait parameters in human walking; however, how speed changes the gait pattern of bipedal locomotion in primates remains unclear. METHODS: We chose six adult female rhesus monkeys (Macaca mulatta) and collected the gait parameters of these animals during their treadmill locomotion over a wide range of speed. Using a 3D motion analysis system, we studied the spatiotemporal characteristics of the gait pattern. RESULTS AND CONCLUSIONS: We have built an efficient and time-saving primate model and shown that speed significantly impacts kinematic parameters. This may present a thorough description of speed-related changes in the gait pattern of rhesus and shed light on the control of bipedal locomotion in primates.


Macaca mulatta/physiology , Walking Speed , Animals , Female , Gait
20.
Neuroradiology ; 58(6): 607-614, 2016 Jun.
Article En | MEDLINE | ID: mdl-26931783

INTRODUCTION: Diffusion tensor imaging (DTI) as a potential technology has been used in spinal cord injury (SCI) studies, but the longitudinal evaluation of DTI parameters after SCI, and the correlation between DTI parameters and locomotor outcomes need to be defined. METHODS: Adult Wistar rats (n = 6) underwent traumatic thoracic cord contusion by an NYU impactor. DTI and Basso-Beattie-Bresnahan datasets were collected pre-SCI and 1, 3, 7, 14, and 84 days post-SCI. Diffusion tensor tractography (DTT) of the spinal cord was also generated. Fractional anisotropy (FA) and connection rate of fibers at the injury epicenter and at 5 mm rostral/caudal to the epicenter were calculated. The variations of these parameters after SCI were observed by one-way analysis of variance and the correlations between these parameters and motor function were explored by Pearson's correlation. RESULTS: FA at the epicenter decreased most remarkably on day 1 post-SCI (from 0.780 ± 0.012 to 0.330 ± 0.015), and continued to decrease slightly by day 3 post-SCI (0.313 ± 0.015), while other parameters decreased significantly over the first 3 days after SCI. DTT showed residual fibers concentrated on ventral and ventrolateral sides of the cord. Moreover, FA at the epicenter exhibited the strongest correlation (r = 0.887, p = 0.000) with the locomotion performance. CONCLUSION: FA was sensitive to degeneration in white matter and DTT could directly reflect the distribution of the residual white matter. Moreover, days 1 to 3 post-SCI may be the optimal time window for SCI examination and therapy.


Aging/pathology , Diffusion Tensor Imaging/methods , Severity of Illness Index , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/pathology , White Matter/diagnostic imaging , White Matter/pathology , Animals , Disease Progression , Female , Image Interpretation, Computer-Assisted/methods , Longitudinal Studies , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity , Spinal Cord Injuries/physiopathology , Subtraction Technique , White Matter/physiopathology
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