Alterations of Regional Homogeneity in Parkinson's Disease Patients With Freezing of Gait: A Resting-State fMRI Study.

OBJECTIVE: The purposes of this study are to investigate the regional homogeneity (ReHo) of spontaneous brain activities in Parkinson's disease (PD) patients with freeze of gait (FOG) and to investigate the neural correlation of movement function through resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: A total of 35 normal controls (NC), 33 PD patients with FOG (FOG+), and 35 PD patients without FOG (FOG-) were enrolled. ReHo was applied to evaluate the regional synchronization of spontaneous brain activities. Analysis of covariance (ANCOVA) was performed on ReHo maps of the three groups, followed by post hoc two-sample t-tests between every two groups. Moreover, the ReHo signals of FOG+ and FOG- were extracted across the whole brain and correlated with movement scores (FOGQ, FOG questionnaire; GFQ, gait and falls questionnaire). RESULTS: Significant ReHo differences were observed in the left cerebrum. Compared to NC subjects, the ReHo of PD subjects was increased in the left angular gyrus (AG) and decreased in the left rolandic operculum/postcentral gyrus (Rol/PostC), left inferior opercular-frontal cortex, left middle occipital gyrus, and supramarginal gyrus (SMG). Compared to that of FOG-, the ReHo of FOG+ was increased in the left caudate and decreased in the left Rol/PostC. Within the significant regions, the ReHo of FOG+ was negatively correlated with FOGQ in the left SMG/PostC (r = -0.39, p < 0.05). Negative correlations were also observed between ReHo and GFQ/FOGQ (r = -0.36/-0.38, p < 0.05) in the left superior temporal gyrus (STG) of the whole brain analysis based on AAL templates. CONCLUSION: The ReHo analysis suggested that the regional signal synchronization of brain activities in FOG+ subjects was most active in the left caudate and most hypoactive in the left Rol/PostC. It also indicated that ReHo in the left caudate and left Rol/PostC was critical for discriminating the three groups. The correlation between ReHo and movement scores (GFQ/FOGQ) in the STG has the potential to differentiate FOG+ from FOG-. This study provided new insight into the understanding of PD with and without FOG.

Altered Global Synchronizations in Patients With Parkinson's Disease: A Resting-State fMRI Study.

Background: Abnormalities of cognitive and movement functions are widely reported in Parkinson's disease (PD). The mechanisms therein are complicated and assumed to a coordination of various brain regions. This study explored the alterations of global synchronizations of brain activities and investigated the neural correlations of cognitive and movement function in PD patients. Methods: Thirty-five age-matched patients with PD and 35 normal controls (NC) were enrolled in resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Degree centrality (DC) was calculated to measure the global synchronizations of brain activity for two groups. Neural correlations between DC and cognitive function Frontal Assessment Battery (FAB), as well as movement function Unified Parkinson's Disease Rating Scale (UPDRS-III), were examined across the whole brain within Anatomical Automatic Labeling (AAL) templates. Results: In the PD group, increased DC was observed in left fusiform gyrus extending to inferior temporal gyrus, left middle temporal gyrus (MTG) and angular gyrus, while it was decreased in right inferior opercular-frontal gyrus extending to superior temporal gyrus (STG). The DC in a significant region of the fusiform gyrus was positively correlated with UPDRS-III scores in PD (r = 0.41, p = 0.0145). Higher FAB scores were shown in NC than PD (p < 0.0001). Correlative analysis of PD between DC and FAB showed negative results (p < 0.05) in frontal cortex, whereas positive in insula and cerebellum. As for the correlations between DC and UPDRS-III, negative correlation (p < 0.05) was observed in bilateral inferior parietal lobule (IPL) and right cerebellum, whereas positive correlation (p < 0.05) in bilateral hippocampus and para-hippocampus gyrus (p < 0.01). Conclusion: The altered global synchronizations revealed altered cognitive and movement functions in PD. The findings suggested that the global functional connectivity in fusiform gyrus, cerebellum and hippocampus gyrus are critical regions in the identification of cognitive and movement functions in PD. This study provides new insights on the interactions among global coordination of brain activity, cognitive and movement functions in PD.

Activation of necroptosis in a rat model of acute respiratory distress syndrome induced by oleic acid.

The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit. Expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissue were determined by Western blot and immunohistochemical staining. The interaction between RIPK1 and RIPK3 was explored by immunoprecipitation. The results showed that, compared with those in control group, total white blood cells count (WBC), polymorphonuclear percentage (PMN%), total protein concentration, TNF-α level in BALF, W/D, and the alveolar-arterial oxygen tension difference (P(A-a)O2) in OA group were significantly increased at 4 h after OA injection. Western blot and immunostaining further showed remarkably increased expressions of RIPK1, RIPK3 and MLKL in lung tissue from OA group. Additionally, immunoprecipitation results indicated an enforced interaction between RIPK1 and RIPK3 in OA group. Collectively, the TNF-α level in BALF and the RIPK1-RIPK3-MLKL signaling pathway in lung tissue were found to be upregulated and activated with the process of ARDS. These findings implicate that RIPK1/RIPK3-mediated necroptosis plays a possible role in the pathogenesis of ARDS, which may provide a new idea to develop novel drugs for the therapy of ARDS.

Necrostatin-1 protects against oleic acid-induced acute respiratory distress syndrome in rats.

Necroptosis is a recently discovered necrotic cell death which is regulated by receptor interacting protein kinase 1 (RIPK1) and RIPK3 under the stimulus of death signal and can be inhibited by necrostatin-1 (Nec-1) specifically. Therefore, the aim was to investigate the role of necroptosis in a rat model of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) and assess the effect of Nec-1 on lung injury in ARDS. Our results found that RIPK1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) were abundantly expressed in rat lung tissues of OA-induced ARDS. Nec-1 pretreatment improved pulmonary function and attenuated lung edema dramatically in OA-induced ARDS rats. Furthermore, Nec-1 reduced RIPK1-RIPK3 interaction and down-regulated RIPK1-RIPK3-MLKL signal pathway, and inhibited inflammatory response by reducing neutrophil infiltration and protein leakage into lung tissue in OA-induced ARDS. Collectively, our study proves the intervention of necroptosis in OA-induced ARDS. Moreover, our findings imply that Nec-1 plays an important role in the treatment of ARDS via inhibiting necroptosis and inflammation.