Increased glymphatic system activity in patients with mild traumatic brain injury.

Purpose: This study aims to investigate the glymphatic system activity changes in patients with mild traumatic brain injury (mTBI), particularly in MRI-negative patients, using analysis along the perivascular space (ALPS) technology. Methods: A total of 161 mTBI patients (age: 15-92 years old) and 28 healthy controls (age: 15-84 years old) were included in this retrospective study. The mTBI patients were divided into MRI-negative and MRI-positive groups. ALPS index was calculated automatically using whole-brain T1-MPRAGE imaging and diffusion tensor imaging. The Student's t and chi-squared tests were performed to compare the ALPS index, age, gender, course of disease, and Glasgow Coma Scale (GCS) score between groups. Correlations among ALPS index, age, course of disease and GCS score were computed using Spearman's correlation analysis. Results: Increased activity of the glymphatic system was suggested in mTBI patients based on ALPS index analysis, including the MRI-negative patients. There was a significant negative correlation between the ALPS index and age. In addition, a weak positive correlation between the ALPS index and course of disease was also observed. On the contrary, there was no significant correlation between the ALPS index and sex nor between the ALPS index and GCS score. Conclusion: Our study demonstrated that the activity level of the glymphatic system was enhanced in mTBI patients, even when their brain MRI scans were negative. These findings may provide novel insights for understanding the pathophysiology of mild TBI.

Bone marrow stromal cells-derived exosomes reduce neurological damage in traumatic brain injury through the miR-124-3p/p38 MAPK/GLT-1 axis.

BACKGROUND: Mounting evidence indicates that stem cell-derived exosomal miRNAs have therapeutic effects on traumatic brain injury (TBI). This research is focused on exploring the molecular processes of miR-124-3p obtained from bone marrow stromal cells-derived exosomes (BMSCs-Exos) in attenuating posttraumatic glutamate-mediated excitotoxicity. METHODS: We created a TBI rat model and analyzed the expression profile of miRNA through miRNA microarray. The miR-124-3p and p38 MAPK levels were analyzed utilizing RT-qPCR and western blotting. Dual-luciferase reporter (DLR) assay showed the targeting relationship between miR-124-3p and p38 MAPK. We subsequently conducted a TUNEL assay and flow cytometry to evaluate the neuronal apoptotic rate in an in vitro glutamate-mediated excitotoxicity model treated with BMSCs-Exos enriched with miR-124-3p (BMSCs-ExosmiR-124-3p). Moreover, the levels of p38 MAPK and glutamate transporter-1 (GLT-1) were measured by western blotting. Furthermore, BMSCs-ExosmiR-124-3p were administered to the TBI rats, and their neuroprotective effects were observed using western blotting, immunohistochemistry, histological staining, magnetic resonance imaging (MRI), and Morris water maze (MWM). RESULTS: The results revealed that the brains of TBI rats exhibited lowered miR-124-3p and enhanced p38 MAPK levels. DLR assay demonstrated miR-124-3p's role in targeting p38 MAPK and negatively regulating its expression. In vitro and in vivo studies confirmed that BMSCs-ExosmiR-124-3p attenuated glutamate-mediated excitotoxicity by downregulating p38 MAPK and upregulating GLT-1 expressions via transferring exosomal miR-124-3p. Moreover, histopathological evaluation and MRI results showed that BMSCs-ExosmiR-124-3p remarkably alleviated neuronal cell death and minimized the lesion volumes post-TBI. MWM outcomes illustrated that BMSCs-ExosmiR-124-3p treatment could substantially improve neurological function post-TBI. Furthermore, the effects of treatment with p38 MAPK inhibitor SB203580 were similar to BMSCs-ExosmiR-124-3p. CONCLUSION: Overall, the outcomes of the current report highlighted that BMSCs-ExosmiR-124-3p can lead to the upregulation of GLT-1 in TBI rat models by inhibiting the p38 MAPK signaling pathway, hence alleviating glutamate-mediated excitotoxicity and attenuating neurological damage post-TBI.

The aging of glymphatic system in human brain and its correlation with brain charts and neuropsychological functioning.

This study aimed to investigate the aging of the glymphatic system in healthy adults, and to determine whether this change is correlated with the brain charts and neuropsychological functioning. Two independent brain 3.0 T MRI datasets were analyzed: a public dataset and our hospital-own dataset from two hospitals. The function of the glymphatic system was quantified by diffusion analysis along the perivascular space (ALPS) index via an automatic method. Brain charts were calculated online. Correlations of the ALPS index with the brain charts, age, gender, and neuropsychological functioning, as well as differences in ALPS index across age groups, were assessed. A total of 161 healthy volunteers ranging in age from 20 to 87 years were included. ALPS index was negatively correlated with the age in both independent datasets. Compared with that of the young group, the ALPS index was significantly lower in the elderly group. No significant difference was found in the ALPS index between different genders. In addition, the ALPS index was not significantly correlated with the brain charts and neuropsychological functioning. In conclusion, the aging of glymphatic system exists in healthy adults, which is not correlated with the changes of brain charts and neuropsychological functioning.

Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI.

Sleep deprivation leads to hippocampal injury. Proteostasis disturbance is an important mechanism linking sleep deprivation and hippocampal injury. However, identifying noninvasive imaging biomarkers for hippocampal proteostasis disturbance remains challenging. Amide proton transfer-weighted (APTw) imaging is a chemical exchange saturation transfer technique based on the amide protons in proteins and peptides. We aimed to explore the ability of APTw imaging in detecting sleep deprivation-induced hippocampal proteostasis disturbance and its biological significance, as well as its biological basis. In vitro, the feasibility of APTw imaging in detecting changes of the protein state was evaluated, demonstrating that APTw imaging can detect alterations in the protein concentration, conformation, and aggregation state. In vivo, the hippocampal APTw signal declined with increased sleep deprivation time and was significantly lower in sleep-deprived rats than that in normal rats. This signal was positively correlated with the number of surviving neurons counted in Nissl staining and negatively correlated with the expression of glucose-regulated protein 78 evaluated in immunohistochemistry. Differentially expressed proteins in proteostasis network pathways were identified in the hippocampi of normal rats and sleep-deprived rats via mass spectrometry proteomics analysis, providing the biological basis for the change of the hippocampal APTw signal in sleep-deprived rats. These findings demonstrate that APTw imaging can detect hippocampal proteostasis disturbance induced by sleep deprivation and reflect the extent of neuronal injury and endoplasmic reticulum stress.

Exosomes derived from bone marrow mesenchymal stem cells attenuate neurological damage in traumatic brain injury by alleviating glutamate-mediated excitotoxicity.

BACKGROUND: Traumatic brain injury (TBI) is one of the major contributors to disability and death worldwide. Glutamate-mediated excitotoxicity, one of the secondary injuries occurring after TBI, leads to extreme neuronal apoptosis, and can be a potential target for intervention. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) have demonstrated neuroprotective effects on TBI. However, their precise role and the underlying mechanism by which they regulate glutamate-mediated excitotoxicity have not yet been determined. Therefore, this study aimed to determine whether BMSCs-Exos alleviate glutamate excitotoxicity post-TBI and their associated mechanism. METHODS: BMSCs-Exos were extracted from the BMSCs incubation medium and identified by transmission electron microscopy, nanoparticle trafficking analysis, and western blotting. The neuroprotective effects of BMSCs-Exos on glutamate excitotoxicity were investigated in the glutamate-mediated excitotoxicity neuronal cell model and the TBI rat model (TBI induced by controlled cortical impact) using western blotting and TUNEL assay. Cortical lesion samples were collected post-TBI on day-1 and day-14 to study histology. In addition, cortical lesion volume on days 1, 3 and 7 following TBI was determined using T2-weighted magnetic resonance imaging (MRI), and cognitive function was assessed at 4 weeks following TBI using the Morris water maze (MWM) test. RESULTS: BMSCs-Exos were observed to be spherical with a mean diameter of 109.9 nm, and expressed exosomal markers CD9, CD81 and TSG101. BMSCs-Exos were efficiently endocytosed by astrocytes after co-incubation for 24 h. In vitro studies revealed that 125 µM of glutamate significantly induced neuronal apoptosis, which was attenuated by BMSCs-Exos in astrocyte-neuron co-cultures. This attenuation was mediated by the upregulation of glutamate transporter-1 (GLT-1) level and the downregulation of p-p38 MAPK level in astrocytes. Similar results were obtained in vivo, wherein we verified that PKH67-labeled BMSCs-Exos administered intravenously could reach the perilesional cortex crossing the blood-brain barrier and significantly reduce glutamate levels in the perilesional cortex of the TBI rat, accompanied by increased GLT-1 level and downregulation in p-p38 MAPK level. Additionally, western blotting and TUNEL staining also revealed that BMSCs-Exos significantly downregulated the expression of pro-apoptosis markers, including cleaved caspase-3 and cleaved caspase-9, and attenuated neuronal apoptosis following TBI. Immunohistochemical analysis and Nissl staining showed that BMSCs-Exos significantly increased GLT-1-positive cells, and the number of apoptotic neurons decreased in the perilesional cortex. Moreover, MRI and MWM results revealed that BMSCs-Exos significantly minimized cortical lesion volume and ameliorated cognitive function after TBI. The underlying neuroprotective mechanism of BMSCs-Exos may be due to an increase in GLT-1 level in astrocytes by blocking the p38 MAPK signaling pathway. CONCLUSION: Taken together, our findings demonstrate that the implementation of BMSCs-Exos may be an effective prospective therapy for attenuating post-TBI neurological damage.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging of Rat Brain With Acute Carbon Monoxide Poisoning.

Objectives: To evaluate the diagnostic and prognostic values of glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging as a quantitative method for pathogenetic research and clinical application of carbon monoxide (CO) poisoning-induced encephalopathy combined with the proton magnetic resonance spectroscopy (1H-MRS) and the related histopathological and behavioral changes. Methods: A total of 63 Sprague-Dawley rats were randomly divided into four groups. Group A (n = 12) was used for animal modeling verification; Group B (n = 15) was used for magnetic resonance molecular imaging, Group C (n = 15) was used for animal behavior experiments, and Group D (n = 21) was used for histopathological examination. All the above quantitative results were analyzed by statistics. Results: The peak value of carboxyhemoglobin saturation in the blood after modeling was 7.3-fold higher than before and lasted at least 2.5 h. The GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than the base values in CO poisoning rats (p < 0.05) and the 1H-MRS showed significant differences in the parietal lobe and hippocampus. In the Morris water maze tests, the average latency and distance were significantly prolonged in poisoned rats (p < 0.05), and the cumulative time was shorter and negatively correlated with GluCEST. Conclusion: The GluCEST imaging non-invasively reflects the changes of glutamate in the brain in vivo with higher sensitivity and spatial resolution than 1H-MRS. Our study implies that GluCEST imaging may be used as a new imaging method for providing a pathogenetic and prognostic assessment of CO-associated encephalopathy.

Using Local Anesthesia for Burr Hole Surgery of Chronic Subdural Hematoma Reduces Postoperative Complications, Length of Stay, and Hospitalization Cost: A Retrospective Cohort Study From a Single Center.

Purpose: The purpose of the current study was to compare the effects of local anesthesia (LA) and general anesthesia (GA) on the surgical process and postoperative recovery of patients with unilateral chronic subdural hematoma (CSDH). Patients and Methods: A retrospective cohort study was conducted on patients with unilateral CSDH who underwent burr hole surgery between the years 2013 and 2018. Patients who received local anesthesia were allocated to the LA group, and the patients who received general anesthesia were allocated to the GA group. The clinical data, postoperative complication, length of stay, and hospitalization cost of these two groups were compared and analyzed. Results: Data from 105 patients was collected for this study. Fifty one patients were assigned to the LA group and 54 to GA group. The duration of anesthesia and operation of the LA group was 37.71 (10.55) min; while for the GA group the duration was 56.04 (8.37) min (p < 0.001). The time from operation to discharge in GA group was greatly longer than that in LA group [(8.51 (1.49) days vs. 10.46 (2.34) days, respectively; p < 0.001]. Hospitalization cost for LA group was 2,721.54 (504.66) USD, which was significantly lesser than that for GA patients [3,314.82 (493.52) USD; p < 0.001]. The total number of complications in LA patients was less than that in GA patients [6 vs. 29 cases, respectively; p < 0.001]. The number of patients with residual hematoma in the LA group was

Combined Application of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Techniques to Investigate the Effect of Iron Deposition on Microstructural Changes in the Brain in Parkinson's Disease.

Objectives: Brain iron deposition and microstructural changes in brain tissue are associated with Parkinson's disease (PD). However, the correlation between these factors in Parkinson's disease has been little studied. This study aimed to use quantitative susceptibility mapping combined with diffusion kurtosis imaging to investigate the effects of iron deposition on microstructural tissue alterations in the brain. Methods: Quantitative susceptibility mapping and diffusion kurtosis imaging were performed on 24 patients with early PD, 13 patients with advanced PD, and 25 healthy controls. The mean values of magnetic susceptibility and diffusion kurtosis were calculated for the bilateral substantia nigra, red nucleus, putamen, globus pallidus, and caudate nucleus, and compared between the groups. Correlation analyses between the diffusion kurtosis of each nucleus and its magnetic susceptibility parameters in PD patients and healthy controls were performed. Results: The study found a significant increase in iron deposition in the substantia nigra, red nucleus, putamen and globus pallidus, bilaterally, in patients with PD. Mean kurtosis values were increased in the substantia nigra but decreased in the globus pallidus; axial kurtosis values were decreased in both the substantia nigra and red nucleus; radial kurtosis values were increased in the substantia nigra but showed an opposite trend in the globus pallidus and caudate nucleus. In the substantia nigra of patients with PD, magnetic susceptibility was positively correlated with mean and radial kurtosis values, and negatively correlated with axial kurtosis. None of these correlations were significantly different in the control group. In the putamen, magnetic susceptibility was positively correlated with mean, axial, and radial kurtosis only in patients with advanced-stage PD. Conclusion: Our study provides new evidence for brain iron content and microstructural alterations in patients with PD. Iron deposition may be a common mechanism for microstructural alterations in the substantia nigra and putamen of patients with PD. Tracking the dynamic changes in iron content and microstructure throughout the course of PD will help us to better understand the dynamics of iron metabolism and microstructural alterations in the pathogenesis of PD and to develop new approaches to monitor and treat PD.

pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke.

Stroke is the second leading cause of death globally and the most common cause of severe disability. Several barriers need to be addressed more effectively to treat stroke, including efficient delivery of therapeutic agents, rapid release at the infarct site, precise imaging of the infarct site, and drug distribution monitoring. The present study aimed to develop a bio-responsive theranostic nanoplatform with signal-amplifying capability to deliver rapamycin (RAPA) to ischemic brain tissues and visually monitor drug distribution. A pH-sensitive theranostic RAPA-loaded nanoparticle system was designed since ischemic tissues have a low-pH microenvironment compared with normal tissues. The nanoparticles demonstrated good stability and biocompatibility and could efficiently load rapamycin, followed by its rapid release in acidic environments, thereby improving therapeutic accuracy. The nano-drug-delivery system also exhibited acid-enhanced magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging signal properties, enabling accurate multimodal imaging with minimal background noise, thus improving drug tracing and diagnostic accuracy. Finally, in vivo experiments confirmed that the nanoparticles preferentially aggregated in the ischemic hemisphere and exerted a neuroprotective effect in rats with transient middle cerebral artery occlusion (tMCAO). These pH-sensitive multifunctional theranostic nanoparticles could serve as a potential nanoplatform for drug tracing as well as the treatment and even diagnosis of acute ischemic stroke. Moreover, they could be a universal solution to achieve accurate in vivo imaging and treatment of other diseases.

Reduced Cerebral Glucose Uptake in an Alzheimer's Rat Model With Glucose-Weighted Chemical Exchange Saturation Transfer Imaging.

A correlation between the abnormal cerebral glucose metabolism and the progression of Alzheimer's disease (AD) has been found in previous studies, suggesting that glucose alterations may be used to predict the histopathological diagnosis in AD. In this study, we investigated the dynamic changes of cerebral glucose uptake in vivo using MR glucose chemical exchange saturation transfer (glucoCEST) imaging in a rat model of AD with an intracerebroventricular (i.c.v) injection of amyloid Aß-protein (25-35), confirmed by Morris water maze and Nissl staining. In total, 6 rats in the AD group and 6 rats in the control group that were given an injection of sterile normal saline were included. At 28 days after injection, all rats performed a 7.0 T MR exanimation, including glucoCEST, diffusion tensor imaging (DTI) and hippocampus magnetic resonance spectra (MRS), to detect the possible metabolic and structural changes in the rat brain. A significantly elevated brain glucoCEST signal in the brain of AD rats was observed, and a decreased brain glucose uptake was also explored during the progression of glucose infusion compared with those in rats of the control group. In addition, there is a significant positive correlation between glucoCEST enhancement (GCE) and myo-Inosito (Ins) in the AD group and the control group (P < 0.05). A significantly reduced number of neurons in the cortex and hippocampus in AD rats combined with the significantly longer escape and a decreased number of crossings were verified at 28 days after Aß25-35 injection by Nissl staining and Morris water maze, respectively. Our results indicated that an abnormal brain glucose mechanism in AD rats could be detected by glucoCEST imaging, suggesting a new method to explore the occurrence and progress of diabetes-related AD or dementia.

Mapping the Alterations of Glutamate Using Glu-Weighted CEST MRI in a Rat Model of Fatigue.

Objective: Glutamate dysregulation may play an important role in the pathophysiology of fatigue. Glutamate weighted chemical exchange saturation transfer (Glu-weighted CEST) MRI is a recently developed technology which enables measuring glutamate in vivo with high sensitivity and spatial resolution. The purpose of this study is to map the alternations of brain glutamate in a rat model of fatigue. Methods: Rats were subjected to 10 days fatigue loading procedure (fatigue group) or reared without any fatigue loading (control group). Spontaneous activities of rats in the fatigue group were recorded from 3 days before fatigue loading to 4 days after the end of fatigue loading. Glu-weighted CEST were performed following 10-day fatigue loading. Results: Rats in the fatigue group exhibited significant reduced spontaneous activities after 10-day fatigue loading. The glutamate level in the whole brain increased significantly in the fatigue group compared to that in the control group. Further analysis of glutamate in the sub-regions of brain including the prefrontal cortex, hippocampus, and striatum revealed a trend of increment, although statistical significance was not reached. Significance: The increase of glutamate level in the brain may be a crucial process involved in the pathophysiology of fatigue.

Imaging of glutamate in acute traumatic brain injury using chemical exchange saturation transfer.

BACKGROUND: Chemical exchange saturation transfer (CEST) is an important contrast mechanism in the field of magnetic resonance imaging. Herein, we used CEST for glutamate (GluCEST) imaging to evaluate the Glu alterations in acute mild to moderate traumatic brain injury (TBI) and correlated such alterations with the cognitive outcome at 1-month postinjury. METHODS: Thirty-two patients with well-documented mild-to-moderate TBI and 15 healthy controls (HC group) underwent 3.0-Tesla magnetic resonance imaging (MRI) with GluCEST, and magnetic resonance spectroscopy (MRS) scans. The Montreal Cognitive Assessment (MoCA) examination was administered to all study subjects at 1-month postinjury for cognitive outcome acquisition and divided TBI patients into patients with good cognitive outcome (GCO group) and with poor cognitive outcome (PCO group). RESULTS: The GluCEST% values for the occipital gray matter (OGM) and bilateral parietooccipital white matter (PWM) were higher in the PCO group compared with the HC and GCO groups (P<0.05), whereas the GluCEST% value showed no significant differences between the GCO and HC groups (P>0.05). In comparison with HCs, TBI patients had a significantly increased GluCEST% value for the OGM and bilateral PWM (P<0.05). GluCEST performed better than MRS in the prediction of cognitive outcome for TBI patients (P<0.05). CONCLUSIONS: Glu is significantly increased in acute TBI and strongly correlates with the cognitive outcome at 1month postinjury. GluCEST may supply new insight into TBI and help to improve the accuracy of short-term outcome prediction.

An Amyloid-ß Targeting Chemical Exchange Saturation Transfer Probe for In Vivo Detection of Alzheimer's Disease.

A reliable and reproducible detection of Aß deposits would be beneficial for the early diagnosis of Alzheimer's disease (AD). In the present study, the feasibility of applying chemical exchange saturation transfer (CEST) for Aß deposit detection using angiopep-2 as a probe was evaluated, and it was demonstrated that CEST could detect angiopep-2 and Aß-angiopep-2 aggregates in vitro. Furthermore, APP/PS1 mice injected with angiopep-2 exhibited a significantly higher in vivo CEST effect when compared with controls. The distribution of Aß deposits detected by CEST imaging was consistent with the histological staining results. The present study is the first to report a reliable exogenous CEST probe to noninvasively evaluate Aß deposits in APP/PS1 mice. Furthermore, these results demonstrate the potential for clinical AD diagnosis and Aß-targeted drug therapy assessment using CEST imaging with the angiopep-2 probe.

Mapping the Changes of Glutamate Using Glutamate Chemical Exchange Saturation Transfer (GluCEST) Technique in a Traumatic Brain Injury Model: A Longitudinal Pilot Study.

Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague-Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.

Three new piscidins from orange-spotted grouper (Epinephelus coioides): Phylogeny, expression and functional characterization.

The present study reports the identification, and characterization of three new putative piscidin paralogues, ecPis-2, ecPis-3 and ecPis-4, from orange-spotted grouper (Epinephelus coioides). The cDNA of the three piscidins with the 207, 216, and 231 nt open reading frame encoded respectively a 68-, 71-, and 76-amino acid preprotein consisting of the predicted signal peptide, and putative mature peptide and prodomain. The phylogenetic analysis indicated that multiple piscidin paralogues in one fish species are highly diversified, the analysis suggested that the piscidins should be a family belonging to the superfamily of ancient cationic, linear, and amphipathic host defence peptides widespread across invertebrate and vertebrate taxa comprising insect cecropins and ceratotoxins, and the amphibian dermaseptins. The synthetic putative mature peptides, ecPis-2S, ecPis-3S and ecPis-4S, had strong activities against bacterial and fungal species. EcPis-3S exhibited powerful activity against the infective stage of Cryptocaryon irritans, theronts. The full length ecPis-2 and ecPis-4 by removal of signal peptide, ecPis-2L and ecPis-4L respectively, had potency against bacterial, fungal and parasitic species. The peptide ecPis-2S was proved to exist in spleen of orange-spotted grouper by HPLC followed by ESI-LCMS analysis. Basal transcriptions of ecPis-2, ecPis-3 and ecPis-4 were detected not only in the potential sites of pathogen entry such as gills, skin and intestine, but also in tissues such as head kidney, trunk kidney, blood cells, and spleen with highly abundant immune cells, however different paralogues expressed constitutively with different levels in the tissues. In addition, the expression of ecPis-2, ecPis-3 and ecPis-4 was upregulated in orange-spotted grouper challenged by Vibrio Parahaemolyticus, in different tissues at different time point after bacteria injection. These results support ecPis-2, ecPis-3 and ecPis-4 being the important immune-related genes in orange-spotted grouper innate immune system and playing multifunctional and complementary roles following their structural and functional diversification, and expression pattern difference. Finally, this study facilitates the evaluation of ecPis-2S, 2L, ecPis-3S, and ecPis-4S, -4L as potential templates of therapeutic agents against pathogens.

Nuclear Overhauser Enhancement-Mediated Magnetization Transfer Imaging in Glioma with Different Progression at 7 T.

Glioma is a malignant neoplasm affecting the central nervous system. The conventional approaches to diagnosis, such as T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1WI, give an oversimplified representation of anatomic structures. Nuclear Overhauser enhancement (NOE) imaging is a special form of magnetization transfer (MT) that provides a new way to detect small solute pools through indirect measurement of attenuated water signals, and makes it possible to probe semisolid macromolecular protons. In this study, we investigated the correlation between the effect of NOE-mediated imaging and progression of glioma in a rat tumor model. We found that the NOE signal decreased in tumor region, and signal of tumor center and peritumoral normal tissue markedly decreased with growth of the glioma. At the same time, NOE signal in contralateral normal tissue dropped relatively late (at about day 16-20 after implanting the glioma cells). NOE imaging is a new contrast method that may provide helpful insights into the pathophysiology of glioma with regard to mobile proteins, lipids, and other metabolites. Further, NOE images differentiate normal brain tissue from glioma tissue at a molecular level. Our study indicates that NOE-mediated imaging is a new and promising approach for estimation of tumor progression.

Hepatoma-derived growth factor-2 is highly expressed during development and in spinal cord injury.

Hepatoma­derived growth factor­2 (HDGF­2) is expressed in neurons, astrocytes and oligodendrocytes of the adult mouse brain. However, it has remained elusive whether HDGF­2 is expressed in the spinal cord and is involved in the its development and repair. In the present study, the expression of HDGF­2 was investigated in rat spinal cords at different developmental stages and following spinal cord injury (SCI). Protein levels of HDGF­2 were examined using western blot analysis, while the distribution pattern and cell populations of HDGF­2 protein expression were characterized using immunohistochemistry. Western blot analysis demonstrated that the levels of HDGF­2 protein expression were the greatest in the spinal cord on embryonic day 19, and were also highly expressed in rat spinal cords on post­natal day 7 (P7); however, they were low at P14 and not detectable at two months. HDGF­2 expression was significantly upregulated in the embryonic spinal cord and injured spinal cord. By contrast, the expression of HDGF­2 was low in uninjured adult spinal cords. HDGF­2 expression in the fetal rat spinal cord and injured spinal cord was significantly higher than that in uninjured adult spinal cord tissues (P<0.05). The number of cells positive for HDGF­2 was 141±62, 107±33 and 92±18 at days 1, 21 and 45 following SCI, respectively, as opposed to 50±9 in uninjured rats, and a significant difference was identified between the different time­points following SCI (P<0.01). In conclusion, the overexpression of HDGF­2 in the embryonic spinal cord and injured spinal cord may be involved in fetal spinal cord development and repair of SCI, respectively.

The clinical and CT features of rapid spontaneous resolution of traumatic acute subdural hematoma: A retrospective study of 14 cases.

OBJECTIVE: Resolution of a traumatic acute subdural haematoma (ASDH) requires weeks or months. However, cases of rapid spontaneous resolution of ASDH within 72 hours after trauma have been reported. The purpose of this study was to obtain a better understanding of the clinical and CT features of cases of rapid resolution following traumatic ASDH. METHOD: Between 2011-2014, the authors retrospectively collected data from 14 patients with rapid resolution of traumatic ASDH. The clinical data and CT findings of these cases were collected and analysed. RESULTS: In 13 of the 14 patients, there was a rapid spontaneous resolution of the ASDH within 48 hours. The mean haematoma width of the second CT was significantly smaller than the width of the initial CT. A significantly marked resolution of the midline shift was observed in the second CT in all patients. The outcome was good in the majority of patients. CONCLUSIONS: The acute fluctuation of ICP may drive the spontaneous rapid resolution and redistribution of ASDH. Patients with abnormal coagulant function may be more likely to experience rapid resolution of ASDH. A band of low density in the initial CT image may be a useful sign for rapid resolution of ASDH.