Optic Nerve Sheath Measurements by Computed Tomography to Predict Intracranial Pressure and Guide Surgery in Patients with Traumatic Brain Injury.

BACKGROUND: Research has shown that the optic nerve sheath diameter (ONSD) is a good predictor of intracranial pressure (ICP) and may predict the need for surgery in patients with head injury. The objective was to test the value of ONSD in predicting the requirement for surgery in patients with traumatic brain injury (TBI). METHODS: In this retrospective cohort study, we first verified the correlation between ICP and ONSD using data from 62 patients with TBI who had undergone ICP monitoring. Second, we analyzed head computed tomography images from patients with TBI who were admitted to the emergency department where patients had been divided into surgery or conservative treatment groups, dependent on the assessment of a neurosurgeon. The correlation between ICP and ONSD was measured using linear regression analysis. Biologistic and receiver operating characteristic curve analyses were used to test the diagnostic value of ONSD to predict surgery. RESULTS: ONSD was significantly correlated with ICP (r = 0.606; P < 0.01), and there was a significant linear regression equation (y = 0.071 × ICP + 3.533; P < 0.01), with ONSD predicting the requirement for surgery in patients with TBI (area under the curve, 0.920; P < 0.01; 95% confidence interval, 0.877-0.962). CONCLUSIONS: ONSD measured via head computed tomography correlates with ICP and can predict the requirement for surgery in patients with TBI following admission to the emergency department.

Exogenous Tetranectin Protects Against 1-Methyl-4-Phenylpyridine-Induced Neurotoxicity by Inhibiting Apoptosis and Autophagy Through Ribosomal Protein S6 Kinase Beta-1.

BACKGROUND: Tetranectin is a secreted homotrimeric protein belonging to the C-type lectin family. Our previous studies found that tetranectin was not only related to, but also played a protective role in, Parkinson disease. In this study, we aim to illustrate the molecular mechanism of the secreted tetranectin. METHODS: We used exogenous tetranectin to investigate the function and molecular mechanism of secreted tetranectin in a 1-methyl-4-phenylpyridine (MPP+)-induced SH-SY5Y cell model. Cell viability and reactive oxygen species were measured to assess the protective effects of tetranectin against MPP+. Apoptosis was measured in several aspects, including Bcl-2/Bax expression, caspase-3/7 activity, annexin V staining, and nuclear morphology. Autophagy was measured as LC3 expression and autophagy flux. Moreover, we used cell immunofluorescence to detect the transport of tetranectin. Western blotting was performed to measure the phosphorylation level of ribosomal protein S6 kinase beta-1 (p70S6K1), and co-immunoprecipitation was applied to confirm the interaction between tetranectin and p70S6K1. RESULTS: The data showed exogenous tetranectin alleviated MPP+-induced toxicity, high reactive oxygen species levels, apoptosis, and autophagy and changed the phosphorylation level of p70S6K1. Immunofluorescence images suggested exogenous tetranectin could be taken into SH-SY5Y cells, and the co-immunoprecipitation experiment indicated tetranectin interacted with p70S6K1. CONCLUSIONS: Exogenous tetranectin protects against MPP+-induced neurotoxicity by promoting p70S6K1 phosphorylation once taken into SH-SY5Y cells.

Neuroprotective effect of docosahexaenoic acid in rat traumatic brain injury model via regulation of TLR4/NF-Kappa B signaling pathway.

OBJECTIVE: The experiments were conducted to prove that docosahexaenoic acid (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B signaling pathway. METHODS: Bioinformatic analysis was performed using published data from Gene Expression Omnibus (GEO) database to investigate differentially expressed genes and signaling pathways. Controlled cortical impact (CCI) injury rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat TBI rats. Neurological severity score (NSS) and beam walking test and rotarod test were used to confirm whether DHA is neuron-protective against TBI. The expression of TLR4, NF-Kappa B p65, (TNF)-α and IL-1ß were examined by qRT-PCR and western blot. The impact of DHA on neurocyte apoptosis was validated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The influence of DHA on CD11b and GFAP expression in the hippocampus was determined through immunohistochemical analysis. RESULTS: TLR4/NF Kappa B pathway was suggested to be closely correlated with TBI by bioinformatic analysis. DHA could improve the neurological function and learning and memory ability of rats after TBI as well as promote neurocytes from apoptosis. TLR4 expression and the expression of inflammatory mediator NF-Kappa B were also repressed by DHA treatment. CONCLUSIONS: DHA exerted a neuron-protective influence in a rat model of TBI via repressing TLR4/NF-Kappa B pathway.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

BACKGROUND: The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). METHODS: We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. RESULTS: After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. CONCLUSIONS: Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS.

BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and attenuates cerebral ischemic injury in stroke.

Stroke is one of the three diseases that cause human death in current world, and it is the common, frequently occurring disease in the middle-old ages. NMDA receptors mediate glutamate-induced cell death when intensely or chronically activated, which is an important cause of neuronal cell death after acute injuries. Here, we demonstrated that BQ-869, a potent NMDA receptor antagonist, blocked NMDA receptor in concentration-dependent and dose-dependent manner, attenuated NMDA-induced Ca(2+) influx, inhabited NMDAR-mEPSC in hippocampal pyramidal neurons, improved athletic ability of rats with MACO, decreased infarction size in focal cerebral ischemia rats and reduced stroke mortality. Taken together, our data demonstrate the neuroprotective effect of BQ-869 might be through inhibiting NMDA-mediated excitotoxicity. These findings indicate that BQ-869 is the most potent antagonist of NMDA receptors, and provide new insights with potential therapeutic applications for the treatment of stroke.

Tetranectin knockout mice develop features of Parkinson disease.

BACKGROUND/AIMS: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs) may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD). Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. METHODS: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN) gene (TN(-/-)) and measured the behavioral and histopathological features of PD. RESULTS: Aged (15-to 20-month-old) TN(-/-) mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia) and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc) and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT) mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. CONCLUSION: The TN(-/-) mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

Proteomic analysis of the cerebrospinal fluid of Parkinson's disease patients pre- and post-deep brain stimulation.

AIMS: To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action . METHODS: Cerebrospinal fluid (CSF), obtained from six Parkinson's disease (PD) patients (pre- and post-DBS) and from six normal healthy controls, was studied for differentially expressed proteins. 2-D DIGE, in combination with MALDI-TOF and TOF-TOF Mass Spectrometry (MS) or ESI-MS, was used to identify the changed proteins (3 PD patients and 3 controls). Selected proteins were further studied using western blotting (6 PD patients and 6 controls). RESULTS: Twenty-one proteins were identified after MS and protein database interrogation. Apart from apolipoprotein A-I (apoA-I), the expression levels of complement C4 (C4), IgA, tetranectin, and extracellular superoxide dismutase (EC-SOD), detected by western blotting, correlated well with the 2-D DIGE results. In the follow-up period, the expression levels of C4, apoA-I and IgA were stable whereas EC-SOD and tetranectin were significantly elevated. In addition, when DBS was ceased in one patient due to a suicide attempt, the levels of EC-SOD and tetranectin significantly decreased. CONCLUSION: Our preliminary results suggest that variations in the expression levels of EC-SOD and tetranectin in CSF is related to DBS.

[Reoperative valve replacement in patients undergoing cardiac reoperation: a report of 104 cases].

OBJECTIVE: To review the experience of reoperative valve replacement for 104 patients. METHODS: From January 2002 to December 2009, 104 patients underwent heart valve replacement in reoperations, accounting for 2.92% of the total patient population (3557 cases) who had valve replacement during this period. In this group, 53 male and 51 female patients were included with a median age of 46 years (ranged from 13 to 72 years). The reasons of reoperation included 28 cases suffered from another valve lesion after valve replacement, 10 cases suffered from valve lesion after mitral valvuloplasty, 19 cases suffered from perivalvular leakage after valve replacement, 18 cases suffered from valve lesion after previous correction of congenital heart defect, 7 cases suffered from bioprosthetic valve decline, 10 cases suffered from prosthetic valve endocarditis, 9 cases suffered from dysfunction of machine valve, and 3 cases suffered from other causes. The re-operations were mitral and aortic valve replacement in 2 cases, mitral valve replacement in 59 cases, aortic valve replacement in 24 cases, tricuspid valve replacement in 16 cases, and Bentall's operation in 3 cases. The interval from first operation to next operation was 1 month-19 years. RESULTS: There were 8 early deaths from heart failure, renal failure and multiple organ failure (early mortality 7.69%). Major complications were intraoperative hemorrhage in 2 cases, re-exploration for mediastinal bleeding in 2 cases and sternotomy surgical site infection in 1 case. Complete follow-up (3 months-7 years and 2 months) was available for all patients. Two patients died, one patient died of intracranial hemorrhage, and another cause was unknown. CONCLUSION: Satisfactory short-term and long-term results can be obtained in reoperative valve replacement with appropriate timing of operation control, satisfactory myocardial protection, accurate surgical procedure and suitable perioperative treatment.

[Experiences on surgical treatment of severe aortic valve stenosis: a report of 171 cases].

OBJECTIVE: To analyze the experiences on surgical treatment of severe aortic valve stenosis. METHODS: From December 1990 to December 2006, 171 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR). There were 135 males and 36 females aged from 10 to 75 years old, with a mean of (45.8 +/- 15.6) years old. The intervals between the first episode of exertion dyspnea and administration to operation were 2 months to 52 years. The pathological lesions of the group were rheumatic aortic valve stenosis in 75 cases, calcified aortic stenosis in 66 cases, bicuspid aortic valve in 26 cases and other congenital aortic valve stenosis in 4 cases. One hundred and twenty-four patients underwent AVR, 7 AVR combined with replacement of the ascending aorta, 5 AVR with coronary artery bypass grafting, 19 AVR with mitral valve plasty (MVP), 8 AVR with plasty of the ascending aorta and 8 AVR with enlargement of the aortic root. RESULTS: The averaged operation time was (4.4 +/- 0.6) h. Cardiopulmonary bypass (CPB) time was (124.7 +/- 38.5) min and the aorta clamp time was (78.3 +/- 21.7) min. The averaged blood loss during operation was (754.5 +/- 518.4) ml. All the procedures were successfully performed and all patients were weaned off CPB uneventfully. The indication of early complications was 12.3% (21/171), including low cardiac output syndrome in 7 cases, multi-organ failure in 3 cases, endocarditis in 1 case, renal dysfunction in 4 cases, ventricular fibrillation in 1 case, excessive bleeding in 2 cases, III atrial-ventricular block in 2 cases, and mediastinal infection in 1 case. The total mortality was 5.8% (10/171) with the main causes as cardiac failure for 4 cases, arrhythmia for 1 case, multi-organ failure for 4 cases, and infectious endocarditis for 1 case. CONCLUSIONS: Successful management of severe aortic valve stenosis requires sophisticated surgical techniques and experienced peri-operative care. Satisfactory results can be achieved if valve replace surgery is performed adequately.

[Aortic valve replacement: the experiences of 1026 cases].

OBJECTIVE: To study the changes in pathogenic causes and the prognosis of aortic valve replacement (AVR). METHODS: The clinical data of 1026 patients undergoing AVR from December 1980 to December 2006 were analyzed retrospectively. The mortality, morbidity, changes in pathogenic causes and risk factors were analyzed. RESULTS: The postoperative mortality and complication morbidity were 4.3% and 10.6% respectively within 30 days followed operation. Main causes of operative death were heart failure, multi organ failure and endocarditis. The major risk factors for operative death were left ventricle ejection fraction less than 0.4, endocarditis, valve regurgitation and emergency operation before AVR. Late mortality was 0.54% patient-year (3.4%), most of whom died of heart failure, endocarditis and arrhythmias. Patients underwent reoperation 0.22% patient-year (1.4%), with the causes of endocarditis and perivalvular fistula. CONCLUSIONS: Morbidity of rheumatic damage in aortic valve has decreased, while valve degeneration has increased gradually in the recent years. Avoiding prosthesis-patient mismatch, good postoperatively guide and prevention of endocarditis can improve the prognosis of AVR.

[Diagnosis and surgical management of primary cardiac neoplasms].

OBJECTIVE: To review and summarize the experience in diagnosis and surgical management of primary cardiac neoplasms. METHODS: 112 patients with primary cardiac neoplasms were treated surgically from Jan. 1980 to Jan. 2005. Those tumors were grouped into three categories: myxomas (98), benign nonmyxomas (3), and malignant tumors (11). Five of 11 malignant tumor patients underwent biopsy or palliative operation, the other patients received complete excision. Mitral valve replacement were done simultaneously in 2 of these patients, mitral valve repair in 4 and tricuspid valvoplasty in 33. All patients' diagnosis was confirmed by echocardiography. RESULTS: 108 patients survived the operation and 4 patients died postoperatively. The hospital mortality was 3.6% (4/112). Two patients developed poor left ventricular function postoperatively and died at the third and the seventh postoperative day due to low cardiac output. One patient developed and died of progressive hepatic and renal function failure postoperatively. Another one patient died of severe arrhythmia. Mean follow-up of 76 myxoma patients who are still alive was 6.4 years (range, 3 month to 17 years). Fifty-five patients still had heart function in New York Heart Association class I and 21 in class II at the end of follow-up without any evidence of recurrance. The follow-up results of benign nonmyxomas were similar to those of myxomas. Mean follow-up of all survived malignant tumor patient was 6 months (range, 2 months to 12 months). Ten of them died of recurrence or metastasis within 1 year postoperatively except only one still alive. CONCLUSION: Surgical resection, whenever possible, is the first treatment choice for all kinds of primary cardiac tumors. Surgical resection of myxoma and benign nonmyxoma can give excellent long-term results which may lead to eventual cure of myxoma and benign nonmyxoma. For malignant tumor patient, surgical treatment is only palliative and to prolong the life of patients.