ABSTRACT
Objective To noninvasively predict isocitrate dehydrogenase(IDH)status of glioma via combining imaging and clini-cal features before surgery,so as to provide basis for individualized clinical treatment decision.Methods A total of 47 patients with glioma confirmed by pathological and molecular genetic tests were included,including 20 with IDH mutant type and 27 with IDH wild type.After diffusion tensor imaging(DTI)scanning,fractional anisotropy(FA)and mean diffusivity(MD)values of tumor paren-chyma were calculated.Combining DTI parameters with MRI morphological features of tumor,blood neutrophil/lymphocyte ratio(NLR)and patient's age,binary logistic regression model was established to effectively predict IDH status of glioma patients before surgery.Results There were significant differences in FAmean/FANAWM,MDmin,NLR,tumor location and age between IDH mutant type and IDH wild type groups(P<0.05).The binary logistic regression model concluding,FAmean/FANAWM,MDmin,cystic degeneration,NLR and age,predicted IDH status of glioma with area under the curve(AUC)of 0.961 and 95%confidence interval(CI)of 0.914-1.00.Conclusion The regression model established via combining DTI,MRI morphological features and blood NLR has great performance in classifying IDH status of glioma,and can help predict IDH status noninvasively before surgery,so as to assist clinical individualized treatment.
ABSTRACT
Objective: To observe the differences of dynamic connectivity in motor function networks between meningioma and low-grade glioma. Methods: Totally 14 patients with meningioma (meningioma group), 14 patients with low grade gliomas (gliomas group) and 14 healthy controls (control group) were enrolled. The wavelet transform coherence (WTC) was used to analyze the dynamic connectivity in motor function networks of 3 groups. Results: The motor function networks nodes were determined by hands movement task stimulus and the generalized linear model analysis, which located at the left and right side of the primary motor cortex (LPMC and RPMC) and the supplementary motor area (SMA). The values of WTC in LPMC-SMA, RPMC-SMA and LPMC-RPMC in meningioma group and gliomas group were lower than those in control group, and in gliomas group were lower than those in meningioma group (all P<0.05). Conclusion: Low frequency fluctuation alteration of connectivity in motor function networks in patients with meningioma and low grade gliomas can be sensitively detected using WTC.
ABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.
Subject(s)
Animals , Humans , Blood-Brain Barrier , Dopaminergic Neurons , Pathology , Inflammation , Pathology , Microglia , Parkinson Disease , Pathology , Substantia Nigra , Pathology , alpha-SynucleinABSTRACT
Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to study white and gray matter (GM) micro-organization and structural connectivity in the brain. Super-resolution track-density imaging (TDI) is an image reconstruction method for dMRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI (stTDI), a variation of TDI with enhanced contrast for GM structures, to reconstruct direction-encoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging (DTI) method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with stTDI, but not with DTI reconstructions from the same dMRI data. The possible mechanisms underlying the enhanced GM contrast are discussed.
Subject(s)
Animals , Male , Brain Mapping , Diffusion Tensor Imaging , Methods , Hippocampus , Diagnostic Imaging , Image Processing, Computer-Assisted , Methods , Neural Pathways , Diagnostic Imaging , Tupaiidae , Visual Cortex , Diagnostic ImagingABSTRACT
OBJECTIVE: To identify the optimal factors in diffusion tensor imaging for predicting corticospinal tract (CST) injury caused by brain tumors. MATERIALS AND METHODS: This prospective study included 33 patients with motor weakness and 64 patients with normal motor function. The movement of the CST, minimum distance between the CST and the tumor, and relative fractional anisotropy (rFA) of the CST on diffusion tensor imaging, were compared between patients with motor weakness and normal function. Logistic regression analysis was used to obtain the optimal factor predicting motor weakness. RESULTS: In patients with motor weakness, the displacement (8.44 ± 6.64 mm) of the CST (p = 0.009), minimum distance (3.98 ± 7.49 mm) between the CST and tumor (p < 0.001), and rFA (0.83 ± 0.11) of the CST (p < 0.001) were significantly different from those of the normal group (4.64 ± 6.65 mm, 14.87 ± 12.04 mm, and 0.98 ± 0.05, respectively) (p = 0.009, p < 0.001, and p < 0.001). The frequencies of patients with the CST passing through the tumor (6%, p = 0.002), CST close to the tumor (23%, p < 0.001), CST close to a malignant tumor (high grade glioma, metastasis, or lymphoma) (19%, p < 0.001), and CST passing through infiltrating edema (19%, p < 0.001) in the motor weakness group, were significantly different from those of the patients with normal motor function (0, 8, 1, and 10%, respectively). Logistic regression analysis showed that decreased rFA and CST close to a malignant tumor were effective variables related to motor weakness. CONCLUSION: Decreased fractional anisotropy, combined with closeness of a malignant tumor to the CST, is the optimal factor in predicting CST injury caused by a brain tumor.
Subject(s)
Humans , Anisotropy , Brain Neoplasms , Brain , Diffusion Tensor Imaging , Diffusion , Edema , Glioma , Logistic Models , Magnetic Resonance Imaging , Neoplasm Metastasis , Prospective Studies , Pyramidal TractsABSTRACT
Acute fetal hypoxia (AFH) can elicit postnatal motor deficits and cognitive impairments. To test whether lifelong acclimatization to middle altitude (MA) hypoxia has protective effects on the impairments caused by AFH, ICR mice bred at 1 900 m altitude for 6-7 generations were evaluated under AFH. On gestation day 9 (GD 9), 13 (GD 13) or 17 (GD 17), pregnant mice received a single exposure to acute hypoxia (7% O, 6 h). Physiological and neurodevelopmental behaviors, motor function (open field), spatial learning and memory (Morris water maze), and anxiety level (elevated plus maze) were examined in the offspring from neonate to adulthood. In the neonatal age, among all the physiological and behavioral landmarks, almost no differences were found in the hypoxia groups. In the juvenile period, no obvious impairments of motor function and anxiety level were found in the hypoxia groups. In the adult period, no obvious impairment of motor function was found in hypoxia groups; Interestingly, AFH groups' offspring showed normal or enhanced long-term spatial memory ability after AFH. These data suggest that AFH cause little abnormalities in the offspring of MA-adapted mice. To further investigate the underlying mechanisms, the neuronal numbers in behavior-related brain areas (accumbens nucleus, basal amygdala and hippocampus) were counted, and the physiological parameters of the blood were measured. The morphological data showed that no obvious neuronal necrosis was found in all hypoxia groups. In addition, blood tests showed that red blood corpuscle count, hemoglobin concentration and hematocrit levels in mice raised at MA were markedly higher in both males and females, compared with controls raised at the sea level. These data suggest that lifelong acclimatization to MA hypoxia has protective effects against development delay, motor deficits and spatial learning and memory impairments induced by AFH, and the protective effects may be due to higher hemoglobin concentration and hematocrit levels in the blood. The findings may provide a better understanding of fetal hypoxia and potential intervention treatments.
ABSTRACT
Traditional Chinese medicine is widely used in the treatment of fractures, osteoporosis, other bone related diseases for thousands of years. There are many animal experiments and clinical trials demonstrating that the traditional Chinese medicine such as epimedium, Drynaria and other traditional Chinese medicine can stimulate bone regeneration and inhibit bone resorption, accelerating the fracture healing. In recent years many cell experiments have shown that these herbal ingredients up-regulated the expression of intracellular osteogenic transcription factors and osteogenic related genes, and then induced osteoblastic differentiation and stimulated the proliferation of osteoblasts, bone nodule formation and matrix mineralization. Meanwhile these herbal ingredients up-regulated the expression of intracellular osteoclastic transcription factors and osteoclast related genes, inhibited osteoclast differentiation and bone resorption of osteoclasts. In addition, intracellular signaling pathways regulated these herbal ingredients by might be involved in the above effects. We can have a conclusion that the genes expression regulated by transcription factors in pre-osteoblast and pre-osteoclast and these signaling pathways are the major molecular mechanisms and research hotspots of traditional Chinese medicine in promoting fracture healing. Based on these molecular mechanisms to review, this review provides not only the foundation for the study of traditional Chinese medicine in promoting fracture healing, but also the basis for clinical treatment of fracture.
ABSTRACT
Objective To investigate the relationship between methylation of CpG island in glutathione S-transferase P1(GSTP1) promoter region and injury induced by isoniazid in HL-7702 cells.Methods HL-7702 cells were divided into the control group and three isoniazid groups(200,400,800 mg/L).Colorimetric method was used to detect the activity level of lactate dehydrogenase in the medium of HL-7702 cells;the mRNA expression of GSTP1,DNA methyltransferases 1(DNMT1),DNMT3a and DNMT3b were de?tected by real-time fluorescence quantitative PCR;the protein expression levels of DNMT1,DNMT3a and DNMT3b were detected by enzyme-linked immunosorbent assay;the methylation of the CpG island in the GSTP1 promoter region was determined by the bisulfite sequencing PCR.Results The activity level of lactate dehydrogenase in supernatants of the HL-7702 cells in isoniazid group(400, 800 mg/L)was higher than that in the control group(P<0.01).Compared with the control group,the mRNA expression of DNMT 1、3a、3b and GSTP1 were elevated in 400 and 800 mg/L isoniazid groups(P<0.05,P<0.01).The proteins expression of DNMT1 and 3a in the 400 and 800 mg/L isoniazid groups were higher than that in the control group(P<0.05,P<0.01),and the protein expression of DNMT 3b in the 800 mg/L isoniazid groups were higher than that in the control group(P<0.01).The methylation level of CpG is?land in GSTP1 promoter region of three isoniazid groups were decreased.Conclusion The CpG island in the promoter of GSTP1 has hypomethylation in hepatocyte cells damaged by isoniazid.
ABSTRACT
Objective To explore the link between the expression of long non-coding RNA(lncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)and IL-6/signal trans ducers and activators of transcription 3(STAT3)signaling pathway in isoniazid induced rats liver injury. Methods Fifty-six specific pathogen-free(SPF)SD rats were randomly divided into experimen?tal group(48 rats)and control group(8 rats),each with half females and half males. The rats in experimental group were given isonia?zid of 63 mg/(kg·d)for 3,7,10,14,21 and 28 d,with 8 rats at the same time point of each day. The rats in control group were giv?en distilled water by intragastric administration. Serum levels of ALT and AST were measured by automatic biochemical analyzer;SYBR green real-time polymerase chain reaction was used to test the expression level of lncRNA MALAT1 and IL-6/STAT3 mRNA in the liver. Results Liver tissue injury occurred after 7 days and worsened with the extention of administration time. Compared with the rats in the control group,the expression level of lncRNA MALAT1 and IL-6/STAT3 mRNA as well as ALT and AST showed a trend of increase(P<0.01). The expression of ALT,AST and lncRNA MALAT1 declined at different degrees on 28(P<0.05). LncRNA MALAT1 and IL-6/STAT3 mRNA expression levels were positively correlated(P<0.01). LncRNA MALAT1 and IL-6/STAT3 mRNA expression levels had a positive correlation with the contents of ALT and AST(P<0.01). Conclusion The expression level of lncRNA MALAT1 in isoniazid induced liver injury rat models showed an abnormal rising trend,and the positive detection time preceded that of ALT and AST. The mechanism may be related to the activation of IL-6/STAT3 signaling pathway.
ABSTRACT
Objective To explore the added value of T2-signal intensity (T2-SI) in discriminating tumor-infiltration from pure vasogenic edema with diffusion tensor imaging (DTI).Methods 55 patients with brain tumors [28 with high-grade glioma (HGG),13 with meningioma,and 14 with metastases] and concurrent peritumoral edema were scanned with DTI.The mean fractional anisotropy (FA),mean diffusivity (MD),longitudinal diffusivity (λ//) and radial diffusivity (λ⊥) in peritumoral edema of different tumors were measured and compared with each other.Results Only the mean FA showed significant difference between edema of HGG and meningioma (P<0.05).When standardized T2-SI was used as the covariant,FA and λ⊥ showed significant differences among the tumor groups.The adjusted FA in edema of HGG was significantly lower than that of metastases (P<0.05) and meningioma (P< 0.001).The adjusted λ⊥ in edema of HGG was significantly higher than that of meningioma (P<0.05).Conclusion By controlling the effect of T2-SI,the value of DTI in distinguishing tumor-infiltration from pure vasogenic edema could be improved.
ABSTRACT
Objective To evaluate the functional features of motor function area in patients with meningioma by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI).Methods fMRI were obtained from 10 patients who suffered from meningioma which was adjacent to the motor function cortex.Probabilistic independent component analysis method was used for data analysis.Preoperative and postoperative line Karnofsky Performance Scale (KPS)score was used to assess the patient’s condition.Re-sults Contralateral primary motor cortex and the supplementary motor cortex motor functions were observed in all the activation clusters,in which one side activation area compared with the contralateral activation zone was symmetrical in 6 cases,and significant shift in 4 cases.In 4 patients with the movement function activated,tumor extrusion function shift forward or backwardwith tensile deforma-tion were found.Conclusion BOLD-fMRI imaging technology can effectively locate motor functional area for patients with meningi-oma,which can provide preoperative surgical planning.
ABSTRACT
<p><b>AIM</b>To explore the changes of MMP-2/9 protein expression and excitation in brain of repetitive hypoxic mice.</p><p><b>METHODS</b>The biochemistry techniques of SDS-PAGE, Western bolt and Gel Goc Image Analysis System were applied to determine the level of MMP-2 and MMP-9 expression and activation in cortex and hippocampus of mice. The animals were randomly divided into 5 groups: the normal control group (H0), acute hypoxic (H1, hypoxic exposure once), repetitive hypoxic groups (H2-H4, repetitive hypoxia for 2-4 runs respectively).</p><p><b>RESULTS</b>(1) The MMP- 2 expression level was increased first then decreased in hippocampus and the significant decrease was found in H4 group (P < 0.05, n=6), but no significant changes among the 5 groups in cortex. In addition, no activated form of 66 kD MMP-2 had been detected both in hippocampus and cortex. (2) Along with the development of brain hypoxic preconditioning, the level MMP-9 protein expression also increased first then decreased gradually in hippocampus, and the significant changes were found both in H1 and H4 groups (P < 0.05, n=7 for each group). The same trace of changes was also found in the activation of MMP-9 (include 82 and 78 kD forms) in hippocampus, and the significance both in H1 and H4 (P < 0.05, n=7 for each group) were detected. However, there was not any significant change in the level of MMP-9 protein expression or activation to be found in cortex.</p><p><b>CONCLUSION</b>These results suggested that MMP-2 and MMP-9 might play certain role in the development of cerebral hypoxic preconditioning, the different changes of MMP-2/9 protein expression and activation both in cortex and hippocampus might be involved in their selective vulnerability to hypoxia.</p>