• Brain-derived cellular microparticles induce systemic coagulopathy in traumatic brain injury.• Platelets facilitate the transmigration of brain microparticles through the endothelial barrier into the circulation.Traumatic brain injury (TBI) is associated with coagulopathy, although it often lacks 2 key risk factors: severe bleeding and significant fluid resuscitation associated with hemorrhagic shock. The pathogenesis of TBI-associated coagulopathy remains poorly understood. We tested the hypothesis that brain-derived microparticles (BDMPs) released from an injured brain induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. Here, we report that mice subjected to fluid percussion injury (1.9 6 0.1 atm) developed a BDMP-dependent hypercoagulable state, with peak levels of plasma glial cell and neuronal BDMPs reaching 17 496 6 4833/mL and 18 388 6 3657/mL 3 hours after TBI, respectively. Uninjured mice injected with BDMPs developed a dosedependent hyper-turned hypocoagulable state measured by a progressively prolonged clotting time, fibrinogen depletion, and microvascular fibrin deposition in multiple organs. The BDMPs were 50 to 300 nm with intact membranes, expressing neuronal or glial cell markers and procoagulant phosphatidylserine and tissue factor. Their procoagulant activity was greater than platelet microparticles and was dose-dependently blocked by lactadherin. Microparticles were produced from injured hippocampal cells, transmigrated through the disrupted endothelial barrier in a platelet-dependent manner, and activated platelets. These data define a novel mechanism of TBI-associated coagulopathy in mice, identify early predictive markers, and provide alternative therapeutic targets. (Blood. 2015;125(13):2151-2159

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BackgroundThe nature and frequency of nonmotor symptoms in primary adult‐onset cervical dystonia (CD) and blepharospasm (BSP) patients in Chinese populations remain unknown.MethodsHamilton's Depression Scale (HAMD), Hamilton's Anxiety Scale (HAMA), Addenbrooke's Cognitive Examination Revised (ACE‐R), Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale were used to evaluate NMS in 120 patients with primary focal adult‐onset dystonia (60 with BSP and 60 with CD) and 60 age‐, sex‐, and education level‐ matched healthy controls (HCs). Motor symptoms of BSP and CD patients were evaluated by Jankovic rating scale and Toronto Western Spasmodic Torticollis Rating Scale‐severity scale separately.ResultsTwenty patients had depression, and 29 patients had anxiety. The mean HAMD and HAMA scores were significantly higher in patient groups. Thirty‐six patients had cognitive decline based on the cut‐off score of 75. The total score and scores of each domain of ACE‐R were significantly lower in patient groups than that in HCs. Quality of sleep was impaired in patient groups, and patients with CD had worse quality of sleep than patients with BSP. Thirty‐three BSP patients and 43 CD patients suffered from sleep disorder separately. The frequency of excessive daytime sleepiness did not differ between patients and HCs. No significant correlation was found between NMS and motor severity in the two forms of dystonia.ConclusionsCurrent study suggests that NMS are prevalent in Chinese CD and BSP patients, and the motor severity of dystonia did not contribute to the severity of nonmotor symptoms. Assessment of nonmotor symptoms should be considered in clinical management of focal dystonia

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The purpose of this study is to investigate whether the topological organization of whole-brain functional network is disrupted in patients with Parkinson's disease (PD). We employed resting-state functional MRI (R-fMRI) and graph theory to investigate the topological organization of the functional connectome in 47 early-stage drug-naïve PD patients and 47 healthy control subjects. Correlations between network properties and clinical variables were tested. Both the PD and control groups showed small-world architecture in brain functional networks. However, the PD patients had lower clustering coefficient and local efficiency relative to control subjects, indicating disrupted topologic organization and a shift toward randomization in their functional brain network. At node and connection level, reduced node centralities and connectivity strength were found mainly in temporal-occipital regions and also in sensorimotor regions of PD patients. In PD patients, altered global network properties correlated with cognitive function, while motor impairment was correlated with local connection changes. This study demonstrates a disruption of whole-brain topological organization of the functional brain networks in early-stage drug-naïve PD patients and this disruption might contribute to preclinical changes in cognitive process in these patients.

Our study demonstrates that PD-Dep patients are characterised by increased regional spontaneous neural activity in the orbitofrontal area and decreased functional integration within the prefrontal-limbic network. These findings may be helpful for facilitating further understanding of the potential mechanisms underlying depression in PD.

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