For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI.SIGNIFICANCE STATEMENTVarying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness.

Presenting a “pleiotropic messenger” strategy using near-infrared–triggered on-demand NO release for spinal cord injury repair.

Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4th, 12th, and 24th weeks; 2) Markwalder’s Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life – the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. ClinicalTrials.gov Identifier – NCT02024373 The date of trial registration: 7 August 2013

Enterobacteriaceae are often found in the lungs of patients with severe Traumatic Brain Injury (sTBI). However, it is unknown whether these bacteria come from the gut microbiota. To investigate this hypothesis, the mice model of sTBI was used in this study. After sTBI, Chao1 and Simpson index peaking at 7 d in the lungs (p < 0.05). The relative abundance of Acinetobacter in the lungs increased to 16.26% at 7 d after sTBI. The chao1 index of gut microbiota increased after sTBI and peaked at 7 d (p < 0.05). Three hours after sTBI, the conditional pathogens such as Lachnoclostridium, Acinetobacter, Bacteroides and Streptococcus grew significantly. At 7 d and 14 d, the histology scores in the sTBI group were significantly higher than the control group (p < 0.05). The myeloperoxidase (MPO) activity increased at all-time points after sTBI and peaked at 7 d (p < 0.05). The LBP and sCD14 peaking 7 d after sTBI (p < 0.05). The Zonulin increased significantly at 3 d after sTBI and maintained the high level (p < 0.05). SourceTracker identified that the lung tissue microbiota reflects 49.69% gut source at 7 d after sTBI. In the small intestine, sTBI induced gastrointestinal dysfunction with increased apoptosis and decreasing antimicrobial peptides. There was a negative correlation between gut conditional pathogens and the expression level of antimicrobial peptides in Paneth cells. Our data indicate that gut bacteria translocated to the lungs after sTBI, and Paneth cells may regulate gut microbiota stability and translocation.