Objective Through establishment of brain slice model in rats with perfusion and oxygen glucose deprivation (OGD), we investigated whether this model can replicate the pathophysiology of brain injury in cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) or not and whether perfusion and OGD can induce preoligodendrocytes (preOL) injury or not, to provide cytological evidence for white matter injury after cardiopulmonary bypass. Methods Three to five living brain slices were randomly obtained from each of forty seven-day-old (P7) Sprague-Dawley (SD) rats with a mean weight of 14.7±1.5 g. Brain slices were randomly divided into five groups with 24 slices in each group: control group with normothermic artificial cerebralspinal fluid (aCSF) perfusion (36℃) and DHCA groups: OGD at 15℃, 25℃, 32℃ and 36℃. The perfusion system was established, and the whole process of CPB and DHCA in cardiac surgery was simulated. The degree of oligodendrocyte injury was evaluated by MBP and O4 antibody via application of immunohistochemistry. Results In the OGD group, the mature oligodendrocytes (MBP-positive) cells were significantly damaged, their morphology was greatly changed and fluorescence expression was significantly reduced. The higher the OGD temperature was, the more serious the damage was; preOL (O4-positive) cells showed different levels of fluorescence expression reduce in 36℃, 32℃ and 25℃ groups, and the higher the OGD temperature was, the more obvious decrease in fluorescence expression was. There was no statistically significant difference in the O4-positive cells between the control group and the 15℃ OGD group. Conclusion The perfused brain slice model is effective to replicate the pathophysiology of brain injury in CPB/DHCA which can induce preOL damage that is in critical development stages of oligodendrocyte cell line, and reduce differentiation of oligodendrocyte cells and eventually leads to hypomyelination as well as cerebral white matter injury.
Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.
Objective To study the impact of chronic hypoxia on white matter (WM) injury and brain development delay using a neonatal rat model, and to explore its value in simulating chronic hypoxic brain damage in cyanotic congenital heart disease (CHD). Methods Three-day-old Sprague-Dawley (SD) rats were randomly distributed to an experiment group (n=36, FiO2 10.5%±1.0%) and a control group (n=36, FiO2 21.0%±0.0%) and were raised for 12 days. (1) Body weight of SD rats was recorded every day and fresh brain weight was measured on P14. (2) H&E staining was performed on sections of brain tissue to observe pathological changes and ventricular size. (3) Immunohistochemistry (IHC) was applied to reveal alterations of oligodendroglial progenitor cells (OPC), preoligodendrocytes (PreOL) and myelin basic protein (MBP) in brain WM area. (4) Protein was extracted from 50 mg of brain tissue in WM area and expression of MBP was determined using Western blotting. (5) Motor function and coordination of rats (P30) were assessed via rotation experiment. Results (1) Body weight and brain weight were significantly less in the experiment group compared with the control group on P14 (body weight 14.92±1.26 gvs. 30.26±1.81 g, t=7.51, P<0.01; brain weight 0.68± 0.05 gvs.0.97±0.04 g, t=13.26, P<0.01); (2) HE staining: Sections of brain tissue from the experiment group showed ventricular size enlargement with a statistical difference (P<0.01), disordered cell organization, local neuronal death and leukomalacia. (3) The number of OPC and PreOL in the experiment group were significantly less than those in the control group (64.8±6.3vs. 126.2±8.4, t=11.19, P<0.01; 19.1±7.6vs. 46.7±9.5, t=7.28, P<0.01, respectively). MBP distribution was sparse and disorganized in the experiment group. (4) Western blotting: Expression of MBP was less in the experiment group (P<0.01). (5) Behavioral test: Time on rotarod was less in the experiment group with a statistical difference (P<0.01). Conclusion Chronic hypoxia can result in WM injury and brain development delay in neonatal rats, with features comparable to those seen in infants with cyanotic CHD.
Objective To explore the difference of white matter changes between bipolar affective disorder and schizophrenia using diffusion tensor imaging (DTI). Methods Patients with bipolar affective disorder and schizophrenia were selected from the Mental Health Center of West China Hospital of Sichuan University between October 2014 and January 2017. Volunteers were recruited from October 2014 to January 2017. The included patients were divided into bipolar affective disorder group and schizophrenia group according to their diagnosis. Volunteers were divided into normal control group. The bipolar affective disorder group was divided into two subgroups: manic episode and depressive episode. DTI was performed on the included patients and volunteers. Tract based spatial statistics (TBSS) was used to study the differences in fractional anisotropy (FA) of white matter between patients and normal controls, and FA values of two subgroups of bipolar affective disorder and schizophrenia were compared. Results A total of 99 patients and 40 normal controls were included in this study. Among them, there were 40 cases in schizophrenia group and 59 cases in bipolar affective disorder group (31 cases of manic episode and 28 cases of depressive episode). Compared with the normal control group, FA values decreased in corpus callosum, fornix, occipital forceps and left inferior longitudinal fasciculus with bipolar affective disorder group and schizophrenia group (P<0.05). There was no significant difference in FA values between bipolar affective disorder group and schizophrenia group (P>0.05), but the FA value in left posterior thalamic radiation decreased in depressive episode of bipolar affective disorder group compared with schizophrenia group (P=0.001). Conclusions There are similarities between white matter changes in bipolar affective disorder and schizophrenia. However, the white matter change in posterior thalamic radiation may be the characteristic change in depressive episode of bipolar affective disorder.
Objective To explore the white matter microstructural abnormalities in patients with different subtypes of attention-deficit/hyperactivity disorder (ADHD) and establish a diagnostic classification model. Methods Patients with ADHD admitted to West China Hospital of Sichuan University between January 2019 and September 2021 and healthy controls recruited through advertisement were prospectively selected. All participants underwent diffusion tensor imaging scanning. The whole brain voxel-based analysis was used to compare the diffusion parameter maps of fractional anisotropy (FA) among patients with combined subtype of ADHD (ADHD-C), patients with inattentive subtype of ADHD (ADHD-I) and healthy controls. The support vector machine classifier and feature selection method were used to construct the individual ADHD diagnostic classification model and efficiency was evaluated between each two groups of the ADHD patients and healthy controls. Results A total of 26 ADHD-C patients, 24 ADHD-I patients and 26 healthy controls were included. The three groups showed significant differences in FA values in the bilateral sagittal stratum of temporal lobe (ADHD-C<ADHD-I<healthy controls) and the isthmus of corpus callosum (ADHD-C>ADHD-I>healthy controls) (P<0.005). The direct comparison between the two subtypes of ADHD showed that ADHD-C had higher FA than ADHD-I in the right middle frontal gyrus. The classification model differentiating ADHD-C and ADHD-I showed the highest efficiency, with a total accuracy of 76.0%, sensitivity of 88.5%, and specificity of 70.8%. Conclusions There is both commonality and heterogeneity in white matter microstructural alterations in the two subtypes of patients with ADHD. The white matter damage of the sagittal stratum of temporal lobe and the corpus callosum may be the intrinsic pathophysiological basis of ADHD, while the anomalies of frontal brain region may be the differential point between different subtypes of patients.
Objective To explore the correlations of serum levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and their ratios, with the severity of white matter hyperintensities (WMH) in patients with cerebral small vessel disease (CSVD). Methods This prospective study included patients with CSVD who were treated at Zhongshan Hospital, Xiamen University between January 2022 and February 2024. Qualitative and quantitative analyses of WMH were performed using the Fazekas scale and lesion prediction algorithm. Biomarkers such as MMP-2, MMP-9, and TIMP-1 were measured to explore their correlations with the severity of WMH. Results A total of 144 patients with CSVD were included in this study, comprising 63 males and 81 females, with an average age of (67.60±8.73) years. There were 83 (57.6%), 41 (28.5%), and 20 (13.9%) patients were categorized as Fazekas grade 1, 2, and 3 for WMH, respectively, with an median total WMH volume of 4.31 mL. Multinomial logistic regression analysis for Fazekas grade (grade 1 as the reference level) showed that MMP-2 [grade 2: odds ratio (OR)=1.059, 95% confidence interval (CI) (1.016, 1.105); grade 3: OR=1.463, 95%CI (1.124, 1.905)], TIMP-1 [grade 2: OR=1.019, 95%CI (1.006, 1.032); grade 3: OR=1.048, 95%CI (1.008, 1.090)], and MMP-9/TIMP-1 [grade 3: OR=2.650, 95%CI (1.393, 5.039)] were independently associated with Fazekas grade (P<0.05). Multinomial logistic regression analysis for the quartile group of total WMH volume (group Q1 as the reference level) showed that MMP-2 [group Q2: OR=1.160, 95%CI (1.021, 1.318); group Q3: OR=1.238, 95%CI (1.086, 1.412); group Q4: OR=1.313, 95%CI (1.140, 1.512)] and TIMP-1 [group Q2: OR=1.095, 95%CI (1.054, 1.138); group Q3: OR=1.084, 95%CI (1.045, 1.125); group Q4: OR=1.102, 95%CI (1.057, 1.149)] were independently associated with the quartile group of total WMH volume (P<0.05). Conclusions Serum levels of MMP-2 and TIMP-1 demonstrate significant independent associations with both the Fazekas grade and the total volume of WMH in patients with CSVD. These correlations underscore the potential utility of MMP-2 and TIMP-1 as critical biomarkers for assessing the severity of WMH in CSVD, highlighting their prospective roles in clinical diagnostics and therapeutic monitoring.