Epidural combined optical and electrical stimulation induces high-specificity activation of target muscles in spinal cord injured rats.

Introduction: Epidural electrical stimulation (EES) has been shown to improve motor dysfunction after spinal cord injury (SCI) by activating residual locomotor neural networks. However, the stimulation current often spreads excessively, leading to activation of non-target muscles and reducing the accuracy of stimulation regulation. Objectives: Near-infrared nerve stimulation (nINS) was combined with EES to explore its regulatory effect on lower limb muscle activity in spinal-cord-transected rats. Methods: In this study, stimulation electrodes were implanted into the rats' L3-L6 spinal cord segment with T8 cord transected. Firstly, a series of EES parameters (0.2-0.6 mA and 20-60 Hz) were tested to determine those that specifically regulate the tibialis anterior (TA) and medial gastrocnemius (MG). Subsequently, to determine the effect of combined optical and electrical stimulation, near-infrared laser with a wavelength of 808 nm was used to irradiate the L3-L6 spinal cord segment while EES was performed. The amplitude of electromyography (EMG), the specific activation intensity of the target muscle, and the minimum stimulus current intensity to induce joint movement (motor threshold) under a series of optical stimulation parameters (power: 0.0-2.0 W; pulse width: 0-10 ms) were investigated and analyzed. Results: EES stimulation with 40 Hz at the L3 and L6 spinal cord segments specifically activated TA and MG, respectively. High stimulation intensity (>2 × motor threshold) activated non-target muscles, while low stimulation frequency (<20 Hz) produced intermittent contraction. Compared to electrical stimulation alone (0.577 ± 0.081 mV), the combined stimulation strategy could induce stronger EMG amplitude of MG (1.426 ± 0.365 mV) after spinal cord injury (p < 0.01). The combined application of nINS effectively decreased the EES-induced motor threshold of MG (from 0.237 ± 0.001 mA to 0.166 ± 0.028 mA, p < 0.001). Additionally, the pulse width (PW) of nINS had a slight impact on the regulation of muscle activity. The EMG amplitude of MG only increased by ~70% (from 3.978 ± 0.240 mV to 6.753 ± 0.263 mV) when the PW increased by 10-fold (from 1 to 10 ms). Conclusion: The study demonstrates the feasibility of epidural combined electrical and optical stimulation for highly specific regulation of muscle activity after SCI, and provides a new strategy for improving motor dysfunction caused by SCI.

Different macaque brain network remodeling after spinal cord injury and NT3 treatment.

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.

Recognition of necrotic regions in MRI images of chronic spinal cord injury based on superpixel.

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.

Rehabilitation Training after Spinal Cord Injury Affects Brain Structure and Function: From Mechanisms to Methods.

Spinal cord injury (SCI) is a serious neurological insult that disrupts the ascending and descending neural pathways between the peripheral nerves and the brain, leading to not only functional deficits in the injured area and below the level of the lesion but also morphological, structural, and functional reorganization of the brain. These changes introduce new challenges and uncertainties into the treatment of SCI. Rehabilitation training, a clinical intervention designed to promote functional recovery after spinal cord and brain injuries, has been reported to promote activation and functional reorganization of the cerebral cortex through multiple physiological mechanisms. In this review, we evaluate the potential mechanisms of exercise that affect the brain structure and function, as well as the rehabilitation training process for the brain after SCI. Additionally, we compare and discuss the principles, effects, and future directions of several rehabilitation training methods that facilitate cerebral cortex activation and recovery after SCI. Understanding the regulatory role of rehabilitation training at the supraspinal center is of great significance for clinicians to develop SCI treatment strategies and optimize rehabilitation plans.

Neural regeneration therapy after spinal cord injury induces unique brain functional reorganizations in rhesus monkeys.

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.

Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar.

Spinal cord injury (SCI) is a severe damage usually leading to limb dysesthesia, motor dysfunction, and other physiological disability. We have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats and non-human primates. Due to the negative effect of inhibitory molecules in glial scar on axonal regeneration, however, the role of NT3-chitosan in the treatment of chronic SCI remains unclear. Compared with the fresh wound of acute SCI, how to handle the lesion core and glial scars is a major issue related to chronic-SCI repair. Here we report, in a chronic complete SCI rat model, establishment of magnetic resonance-diffusion tensor imaging (MR-DTI) methods to monitor spatial and temporal changes of the lesion area, which matched well with anatomical analyses. Clearance of the lesion core via suction of cystic tissues and trimming of solid scar tissues before introducing NT3-chitosan using either a rigid tubular scaffold or a soft gel form led to robust neural regeneration, which interconnected the severed ascending and descending axons and accompanied with electrophysiological and motor functional recovery. In contrast, cystic tissue extraction without scar trimming followed by NT3-chitosan injection, resulted in little, if any regeneration. Taken together, after lesion core clearance, NT3-chitosan can be used to enable chronic-SCI repair and MR-DTI-based mapping of lesion area and monitoring of ongoing regeneration can potentially be implemented in clinical studies for subacute/chronic-SCI repair.

Distribution Heterogeneity of Muscle Spindles Across Skeletal Muscles of Lower Extremities in C57BL/6 Mice.

Muscle spindles, an important proprioceptor scattered in the skeletal muscle, participate in maintaining muscle tension and the fine regulation of random movement. Although muscle spindles exist in all skeletal muscles, explanations about the distribution and morphology of muscle spindles remain lacking for the indetermination of spindle location across muscles. In this study, traditional time-consuming histochemical technology was utilized to determine the muscle spindle anatomical and morphological characteristics in the lower extremity skeletal muscle in C57BL/6 mice. The relative distance from spindles to nerve-entry points varied from muscles in the ventral-dorsal direction, in which spindles in the lateral of gastrocnemius were not considered to be close to its nerve-entry point. In the longitudinal pattern, the domain with the highest abundance of spindles corresponded to the nerve-entry point, excluding the tibialis anterior. Spindles are mainly concentrated at the middle and rostral domain in all muscles. The results suggest a heterogeneity of the distribution of spindles in different muscles, but the distribution trend generally follows the location pattern of the nerve-entry point. Histochemical staining revealed that the spindle did not have a symmetrical structure along the equator, and this result does not agree with previous findings. Exploring the distribution and structural characteristics of muscle spindles in skeletal muscle can provide some anatomical basis for the study of muscle spindles at the molecular level and treatment of exercise-related diseases and provide a comprehensive understanding of muscle spindle morphology.

NT3 treatment alters spinal cord injury-induced changes in the gray matter volume of rhesus monkey cortex.

Spinal cord injury (SCI) may cause structural alterations in brain due to pathophysiological processes, but the effects of SCI treatment on brain have rarely been reported. Here, voxel-based morphometry is employed to investigate the effects of SCI and neurotrophin-3 (NT3) coupled chitosan-induced regeneration on brain and spinal cord structures in rhesus monkeys. Possible association between brain and spinal cord structural alterations is explored. The pain sensitivity and stepping ability of animals are collected to evaluate sensorimotor functional alterations. Compared with SCI, the unique effects of NT3 treatment on brain structure appear in extensive regions which involved in motor control and neuropathic pain, such as right visual cortex, superior parietal lobule, left superior frontal gyrus (SFG), middle frontal gyrus, inferior frontal gyrus, insula, secondary somatosensory cortex, anterior cingulate cortex, and bilateral caudate nucleus. Particularly, the structure of insula is significantly correlated with the pain sensitivity. Regenerative treatment also shows a protective effect on spinal cord structure. The associations between brain and spinal cord structural alterations are observed in right primary somatosensory cortex, SFG, and other regions. These results help further elucidate secondary effects on brain of SCI and provide a basis for evaluating the effects of NT3 treatment on brain structure.

MRI metrics at the epicenter of spinal cord injury are correlated with the stepping process in rhesus monkeys.

Clinical evaluations of long-term outcomes in the early-stage spinal cord injury (SCI) focus on macroscopic motor performance and are limited in their prognostic precision. This study was designed to investigate the sensitivity of the magnetic resonance imaging (MRI) indexes to the data-driven gait process after SCI. Ten adult female rhesus monkeys were subjected to thoracic SCI. Kinematics-based gait examinations were performed at 1 (early stage) and 12 (chronic stage) months post-SCI. The proportion of stepping (PS) and gait stability (GS) were calculated as the outcome measures. MRI metrics, which were derived from structural imaging (spinal cord cross-sectional area, SCA) and diffusion tensor imaging (fractional anisotropy, FA; axial diffusivity, λ//), were acquired in the early stage and compared with functional outcomes by using correlation analysis and stepwise multivariable linear regression. Residual tissue SCA at the injury epicenter and residual tissue FA/remote normal-like tissue FA were correlated with the early-stage PS and GS. The extent of lesion site λ///residual tissue λ// in the early stage after SCI was correlated with the chronic-stage GS. The ratios of lesion site λ// to residual tissue λ// and early-stage GS were predictive of the improvement in the PS at follow-up. Similarly, the ratios of lesion site λ// to residual tissue λ// and early-stage PS best predicted chronic GS recovery. Our findings demonstrate the predictive power of MRI combined with the early data-driven gait indexes for long-term outcomes. Such an approach may help clinicians to predict functional recovery accurately.

[Research progress on muscle spindle morphology].

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.

Importance of brain alterations in spinal cord injury.

Spinal cord injury (SCI) destroys the sensorimotor pathway and blocks the information flow between the peripheral nerve and the brain, resulting in autonomic function loss. Numerous studies have explored the effects of obstructed information flow on brain structure and function and proved the extensive plasticity of the brain after SCI. Great progress has also been achieved in therapeutic strategies for SCI to restore the "re-innervation" of the cerebral cortex to the limbs to some extent. Although no thorough research has been conducted, the changes of brain structure and function caused by "re-domination" have been reported. This article is a review of the recent research progress on local structure, functional changes, and circuit reorganization of the cerebral cortex after SCI. Alterations of structure and electrical activity characteristics of brain neurons, features of brain functional reorganization, and regulation of brain functions by reconfigured information flow were also explored. The integration of brain function is the basis for the human body to exercise complex/fine movements and is intricately and widely regulated by information flow. Hence, its changes after SCI and treatments should be considered.

Effect of b Value on Imaging Quality for Diffusion Tensor Imaging of the Spinal Cord at Ultrahigh Field Strength.

OBJECTIVE: To explore the optimal b value setting for diffusion tensor imaging of rats' spinal cord at ultrahigh field strength (7 T). METHODS: Spinal cord diffusion tensor imaging data were collected from 14 rats (5 healthy, 9 spinal cord injured) with a series of b values (200, 300, 400, 500, 600, 700, 800, 900, and 1000 s/mm2) under the condition that other scanning parameters were consistent. The image quality (including image signal-to-noise ratio and image distortion degree) and data quality (i.e., the stability and consistency of the DTI-derived parameters, referred to as data stability and data consistency) were quantitatively evaluated. The min-max normalization method was used to process the calculation results of the four indicators. Finally, the image and data quality under each b value were synthesized to determine the optimal b value. RESULTS: b = 200 s/mm2 and b = 900 s/mm2 ranked in the top two of the comprehensive evaluation, with the best image quality at b = 200 s/mm2 and the best data quality at b = 900 s/mm2. CONCLUSION: Considering the shortcomings of the ability of low b values to reflect the microstructure, b = 900 s/mm2 can be used as the optimal b value for 7 T spinal cord diffusion tensor scanning.

Image correction for diffusion tensor imaging of Rhesus monkey thoracic spinal cord.

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.

Neuromuscular control pattern in rhesus monkeys during bipedal walking.

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.

Testing Pathological Variation of White Matter Tract in Adult Rats after Severe Spinal Cord Injury with MRI.

The purpose of this study was to assess the pathological variation in white matter tracts in the adult severe thoracic contusion spinal cord injury (SCI) rat models combined with in vivo magnetic resonance imaging (MRI), as well as the effect of spared white matter (WM) quantity on hindlimb motor function recovery. 7.0T MRI was conducted for all experimental animals before SCI and 1, 3, 7, and 14 days after SCI. The variation in the white matter tract in different regions of the spinal cord after SCI was examined by luxol fast blue (LFB) staining, NF200 immunochemistry, and diffusion tensor imaging (DTI) parameters, including fraction anisotropy, mean diffusivity, axial diffusion, and radial diffusivity. Meanwhile, Basso-Beattie-Bresnahan (BBB) open-field scoring was performed to evaluate the behavior of the paraplegic hind limbs. The quantitative analysis showed that spared white matter measures assessed by LFB and MRI had a close correlation (R2 = 0.8508). The percentage of spared white matter area was closely correlated with BBB score (R2 = 0.8460). After SCI, spared white matter in the spinal cord, especially the ventral column WM, played a critical role in motor function restoration. The results suggest that the first three days provides a key time window for SCI protection and treatment; spared white matter, especially in the ventral column, plays a key role in motor function recovery in rats. Additionally, DTI may be an important noninvasive technique to diagnose acute SCI degree as well as a tool to evaluate functional prognosis. During the transition from nerve protection toward clinical treatment after SCI, in vivo DTI may serve as an emerging noninvasive technique to diagnose acute SCI degree and predict the degree of spontaneous functional recovery after SCI.

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

The kinematic recovery process of rhesus monkeys after spinal cord injury.

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.

Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury.

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.

Structural and metabolic changes in the traumatically injured rat brain: high-resolution in vivo proton magnetic resonance spectroscopy at 7 T.

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.

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

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.