Predicting posttraumatic hydrocephalus: derivation and validation of a risk scoring system based on clinical characteristics.

Posttraumatic hydrocephalus (PTH) is a disorder of disturbed cerebrospinal fluid (CSF) dynamics after traumatic brain injury (TBI). It can lead to brain metabolic impairment and dysfunction and has a high risk of clinical deterioration and worse outcomes. The incidence and risk factors for the development of PTH after decompressive craniectomy (DC) has been assessed in previous studies, but rare studies identify patients with higher risk for PTH among all TBI patients. This study aimed to develop and validate a risk scoring system to predict PTH after TBI. Demographics, injury severity, duration of coma, radiologic findings, and DC were evaluated to determine the independent predictors of PTH during hospitalization until 6 months following TBI through logistic regression analysis. A risk stratification system was created by assigning a number of points for each predictor and validated in an independent cohort. The model accuracy was assessed by the area under the receiver operating characteristic curve (AUC). Of 526 patients in the derivation cohort, 57 (10.84%) developed PTH during 6 months follow up. Age > 50 yrs (Odd ratio [OR] = 1.91, 95% confidence interval [CI] 1.09-3.75, 4 points), duration of coma ≥1 w (OR = 5.68, 95% CI 2.57-13.47, 9 points), Fisher grade III (OR = 2.19, 95% CI 1.24-4.36, 5 points) or IV (OR = 3.87, 95% CI 1.93-8.43, 7 points), bilateral DC (OR = 6.13, 95% CI 2.82-18.14, 9 points), and extra herniation after DC (OR = 2.36, 95% CI 1.46-4.92, 5 points) were independently associated with PTH. Rates of PTH for the low- (0-12 points), intermediate- (13-22 points) and high-risk (23-34 points) groups were 1.16%, 35.19% and 78.57% (p < 0.0001). The corresponding rates in the validation cohort, where 17/175 (9.71%) developed PTH, were 1.35%, 37.50% and 81.82% (p < 0.0001). The risk score model exhibited good-excellent discrimination in both cohorts, with AUC of 0.839 versus 0.894 (derivation versus validation) and good calibration (Hosmer-Lemshow p = 0.56 versus 0.68). This model will be useful to identify patients at high risk for PTH who may be candidates for preventive interventions, and to improve their outcomes.

Neuroglobin and Nogo-a as biomarkers for the severity and prognosis of traumatic brain injury.

OBJECTIVE: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis. METHODS: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96 h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed. RESULTS: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient's GCS score on admission (p < 0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p < 0.05). CONCLUSIONS: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

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.

Prevalence of unruptured cerebral aneurysms in Chinese adults aged 35 to 75 years: a cross-sectional study.

BACKGROUND: The reported prevalence of unruptured cerebral aneurysms (UCAs) varies widely. OBJECTIVE: To measure the prevalence of UCAs by using 3-dimensional time-of-flight magnetic resonance angiography in adults aged 35 to 75 years. DESIGN: Cross-sectional study done between June 2007 and June 2011. SETTING: Two communities chosen at random from 2 districts (1 urban and 1 suburban) in Shanghai, China. PARTICIPANTS: 4813 adults aged 35 to 75 years. MEASUREMENTS: Three-dimensional time-of-flight magnetic resonance angiography, interpreted by 3 observers blinded to the participants' information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence. RESULTS: 369 UCAs were found in 336 participants (130 men and 206 women); 4477 participants had no evidence of UCAs. The prevalence was 7.0% overall (95% CI, 6.3% to 7.7%), with 5.5% for men (CI, 4.6% to 6.4%) and 8.4% for women (CI, 7.3% to 9.5%). The overall prevalence of UCAs was higher in women than in men (P < 0.001) and peaked at ages 55 to 64 years in men and women. The UCAs were mostly located in the internal carotid artery (81%), and 90.2% had a maximum diameter less than 5 mm. Mean diameter was larger in women than in men (3.7 mm vs. 3.2 mm; P < 0.009). LIMITATION: Participants were from 2 communities selected from 2 districts in Shanghai, and adults older than 75 years were not studied. CONCLUSION: The overall prevalence of UCAs was 7.0% in Chinese adults aged 35 to 75 years, and most lesions had a diameter less than 5 mm. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Outcomes of antiplatelet therapy for haemorrhage patients after thrombolysis: a prospective study based on susceptibility-weighted imaging.

PURPOSE: The authors evaluated the effect of susceptibility-weighted imaging (SWI) for antiplatelet therapy on post-thrombolysis microbleeds (MB). MATERIALS AND METHODS: A total of 146 patients without symptomatic intracranial haemorrhage on computed tomography after thrombolysis were allocated to two groups: group A (n = 72) received antiplatelets 24 h after recombinant tissue plasminogen activator, regardless of SWI-detected haemorrhage; group B (n = 74) received antiplatelets for patients without SWI-visualised haemorrhage. RESULTS: Haemorrhage was detected by SWI in 22 and 28 patients in groups A and B, respectively. The difference in mean NIHSS (National Institutes of Health Stroke Scale) score in group A between baseline and 6, 24 h, 7, 14 days was -1.6, -1.7, -3.6, -5.9, respectively; in group B, the difference in mean NIHSS score between baseline and 6, 24 h, 7, 14 days was -2.6, -3.3, -5.4, -8.7, respectively. The difference between groups in reduction of mean NIHSS score from baseline was 1.0 (p < 0.001) at 6 h, 1.6 (p < 0.001) at 24 h, 1.8 (p = 0.001) at 7 days and 2.8 (p < 0.001) at 14 days. NIHSS scores at 7, 14 days and modified Rankin scale at 90 days were significantly lower in haemorrhage patients in groups B than in A, whereas the hospital stay was shorter and the rate of favourable outcome at 90 days was higher. CONCLUSION: Our results indicated that SWI was an effective approach for the guidance of antiplatelet therapy in post-thrombolysis MB.

Dose-dependent protective effect of bisperoxovanadium against acute cerebral ischemia in a rat model of ischemia/reperfusion injury.

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose of this study was to identify the optimal neuroprotective dose of bpV when administrated after focal ischemia/reperfusion (I/R) injury in rats. Focal I/R injury was induced using the middle cerebral artery occlusion method. bpV at doses of 0.25, 0.50 and 1.0 mg/kg were injected intraperitoneally just after reperfusion, with saline serving as a vehicle control. A maximal reduction in brain injury was observed with 1.0 mg/kg bpV. This dose of bpV also significantly blocked apoptosis in the penumbral cortex of rats. This beneficial effect was associated with the increasing levels of Akt phosphorylation in the penumbral cortex. These results demonstrate that the pharmacological inhibition of PTEN protects against I/R injury in a dose-dependent manner and the protective effect might be induced through upregulation of the phosphoinositide-3 kinase/Akt pro-survival pathway, suggesting a new therapeutic strategy to combat ischemic brain injury.

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury.

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased. However, when phosphatase actin regulatory factor 1 was knocked down, the water content decreased. We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway, decreased blood-brain barrier permeability, reduced aquaporin 4 and intercellular adhesion molecule 1 expression, inhibited neuroinflammation, and neuronal apoptosis, thereby improving neurological function. The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.

The clinical value of MRA at 3.0 T for the diagnosis and therapeutic planning of patients with subarachnoid haemorrhage.

OBJECTIVE: To evaluate the clinical value of unenhanced magnetic resonance angiography (MRA) at 3.0 T for the diagnosis and therapeutic planning of patients with subarachnoid haemorrhage (SAH). METHODS: A total of 165 patients with SAH were referred for three-dimensional time-of-flight MRA (3D-TOF-MRA) before digital subtraction angiography (DSA). For each aneurysm, 3D-TOF-MRA was used to determine whether the aneurysm was suitable for coil placement with or without balloon/stent-assisted coiling, surgical clipping or conservative treatment. Treatment planning with 3D-TOF-MRA was compared with actual treatment decisions or treatment that had been carried out in each aneurysm decided using DSA. RESULTS: The aneurysm-based evaluation yielded accuracy of 96.9%, sensitivity of 97.6%, specificity of 93.1%, positive predictive value (PPV) of 98.8% and negative predictive value (NPV) of 87.1%, in the detection of intracranial aneurysms. Treatment planning could be correctly made on the basis of aneurysm anatomy and working view by volume rendering (VR) 3D-TOF-MRA with accuracy, sensitivity, specificity, PPV and NPV of 94.9%, 94.0%, 100%, 100% and 74.4%, respectively, on a per aneurysm-based evaluation. CONCLUSIONS: VR 3D-TOF-MRA offers high diagnostic accuracy in the detection of ruptured intracranial aneurysms, and appears to be an effective treatment planning tool for most patients with SAH. KEY POINTS: VR 3D-TOF-MRA offers high diagnostic accuracy for detecting ruptured intracranial aneurysms. • VR 3D-TOF-MRA helps treatment planning for patients with subarachnoid haemorrhage. • 3D-TOF-MRA is non-invasive and avoids using ionising radiation or contrast agents.

A prospective clinical study of routine repeat computed tomography (CT) after traumatic brain injury (TBI).

PURPOSE: To discuss the repeated CT scanning in patients with traumatic brain injury (TBI) and to identify the conditions under which this approach is necessary. METHODS: One hundred and seventy-one patients who suffered TBI but were not surgically treated were divided into two groups: the routine-repeat CT group (n = 89) and the non-routine-repeat CT group (n = 82). The patients' clinical characteristics were compared. T-tests and stepwise logistic regression were used for analysis. Patients in the routine-repeat CT group were divided into three groups according to GCS scores to determine the need for routinely repeated CT scans. RESULTS: The results revealed statistically significant differences between the two groups in terms of neuro-ICU-LOS and LOS (p < 0.01). No significant differences emerged with respect to hospital charges and GCS scores at discharge (p > 0.05). AGE, international normalized ratio (INR), D-dimer concentration (DD), GCS scores and number of hours between the first CT scan and the injury (HCT1) were influential factors of developing progressive haemorrhage. CONCLUSION: The routine-repeat CT group fared better than did the non-routine-repeat CT group. Routinely repeated CTs were minimally effective among those with mild TBI, whereas this procedure demonstrated a significant effect on patients with moderate and severe TBI.

Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice.

Urolithin A (UA) is a natural metabolite produced from polyphenolics in foods such as pomegranates, berries, and nuts. UA is neuroprotective against Parkinson's disease, Alzheimer's disease, and cerebral hemorrhage. However, its effect against traumatic brain injury remains unknown. In this study, we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA. We found that UA greatly reduced brain edema; increased the expression of tight junction proteins in injured cortex; increased the immunopositivity of two neuronal autophagy markers, microtubule-associated protein 1A/B light chain 3A/B (LC3) and p62; downregulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), two regulators of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway; decreased the phosphorylation levels of inhibitor of NFκB (IκB) kinase alpha (IKKα) and nuclear factor kappa B (NFκB), two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway; reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex; and improved mouse neurological function. These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury, and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways, thus reducing neuroinflammation and enhancing autophagy.

DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS.

To evaluate the potential anticancer effects of 1175 FDA-approved drugs, cell viability screening was performed using 25 human cancer cell lines covering 14 human cancer types. Here, we focus on the action of paroxetine, which demonstrated greater toxicity toward human gastric adenocarcinoma cell-line AGS cells compared with the other FDA-approved drugs, exhibiting an IC50 value lower than 10 µM. Evaluation of the underlying novel mechanisms revealed that paroxetine can enhance DNA damage in gastric cancer cells and involves downregulation of Rad51, HR23B and ERCC1 expression and function, as well as nucleotide shortage. Enhancement of autophagy counteracted paroxetine-induced apoptosis but did not affect paroxetine-induced DNA damage. Paroxetine also enhanced ROS generation in AGS cells, but a ROS scavenger did not improve paroxetine-mediated DNA damage, apoptosis, or autophagy, suggesting ROS might play a minor role in paroxetine-induced cell toxicity. In contrast, paroxetine did not enhance DNA damage, apoptosis, or autophagy in another insensitive gastric adenocarcinoma cell-line MKN-45 cells. Interestingly, co-administration of paroxetine with conventional anticancer agents sensitized MKN-45 cells to these agents: co-treated cells showed increased apoptosis relative to MKN-45 cells treated with the anticancer agent alone. Unequivocally, these data suggest that for the first time that paroxetine triggers cytotoxicity and DNA damage in AGS cells at least partly by reducing the gene expression of Rad51, HR23B, and ERCC1. Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.

D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases.

This study sought to describe and evaluate any relationship between D-dimer values and progressive hemorrhagic injury (PHI) after traumatic brain injury (TBI). In patients with TBI, plasma D-dimer was measured while a computed tomography (CT) scan was conducted as soon as the patient was admitted to the emergency department. A series of other clinical and laboratory parameters were also measured and recorded. A logistic multiple regression analysis was used to identify risk factors for PHI. A cohort of 194 patients with TBI was evaluated in this clinical study. Eighty-one (41.8%) patients suffered PHI as determined by a second CT scan. The plasma D-dimer level was higher in patients who demonstrated PHI compared with those who did not (P < 0.001. Using a receiver-operator characteristic curve to predict the possibility by measuring the D-dimer level, a value of 5.00 mg/L was considered the cutoff point, with a sensitivity of 72.8% and a specificity of 78.8%. Eight-four patients had D-dimer levels higher than the cut point value (5.0 mg/L); PHI was seen in 71.4% of these patients and in 19.1% of the other patients (P < 0.01). Factors with P < 0.2 on bivariate analysis were included in a stepwise logistic regression analysis to identify independent risk factors for TBI coagulopathy. Logistic regression analysis showed that the D-dimer value was a predictor of PHI, and the odds ratio (OR) was 1.341 with per milligram per liter (P = 0.020). The stepwise logistic regression also identified that time from injury to the first CT shorter than 2 h (OR = 2.118, P = 0.047), PLT counts lesser than 100 x 109/L (OR = 7.853, P = 0.018), and Fg lower than 2.0 g/L (OR = 3.001, P = 0.012) were risk factors for the development of PHI. When D-dimer values were dichotomized at 5 mg/L, time from injury to the first CT scan was no longer a risk factor statistically while the OR value of D-dimer to the occurrence of PHI elevated to 11.850(P < 0.001). The level of plasma D-dimer after TBI can be a useful prognostic factor for PHI and should be considered in the clinical management of patients in combination with neuroimaging and other data.

3D rotational angiography with volume rendering: the utility in the detection of intracranial aneurysms.

AIMS: The advent of three-dimensional (3D) rotational angiography (3D DSA) challenged the role of digital subtraction angiography (DSA) as a "gold standard" in the diagnosis of intracranial aneurysms. In this study, we report our experiences in diagnosing intracranial aneurysms by using 3D DSA with volume rendering (VR) technique, particularly focusing on its role in depicting additional aneurysms missed by 2D DSA. MATERIALS AND METHODS: One hundred and thirty-eight consecutive patients with known or suspected aneurysms (54 men, 84 women; median age, 55 years; age range, 18-83 years) underwent both conventional DSA and 3D DSA with VR examination simultaneously. The images of 2D DSA or 3D DSA with VR were evaluated by two observers independently for the presence of aneurysms. Then additional aneurysms were decided and depicted. RESULTS: 3D DSA with VR showed 146 aneurysms in 123 (89.1%) of 138 patients and no aneurysms in 15 patients. 2D DSA showed 115 aneurysms in 110 of 137 patients, with one aneurysm in 106 patients each, 2 in 3 patients each and 3 in 1 patient. After reaching a consensus, there were 31 additional aneurysms detected by 3D DSA with VR. 30 aneurysms were <3 mm in maximum diameter with 3 aneurysms ruptured. These additional aneurysms were located in internal carotid artery (ICA, n = 28, 90.32%), anterior cerebral artery (ACA, n = 3, 9.68%). No additional aneurysms were found in either middle cerebral artery (MCA) or vertebrobasilar and posterior cerebral artery (PCA) systems. CONCLUSIONS: 3D DSA, especially VR images, not only clearly reveals aneurysms and aneurysmal morphology, but also detects additional aneurysms missed by 2D DSA, especially small aneurysms less than 3 mm.

Repair of dural defects with electrospun bacterial cellulose membranes in a rabbit experimental model.

To evaluate the advantages and mechanisms involved in repairing rabbit dural defect with a novel electrospun bacterial cellulose (EBC) membrane, a series of experiments were carried out in vitro and in vivo. Compared with common bacterial cellulose (BC) membrane, a more dispersed and regular fiber structure and a better porosity and water holding capacity were found in the EBC membrane, which also had superior degradability. However, the biomechanical properties were slightly decreased. The results demonstrated that BC and EBC membranes had little effect on proliferation and apoptosis of mouse fibroblast cells. There were no complications such as infection, cerebrospinal fluid leakage, epilepsy and brain swelling after BC and EBC membrane repairs in rabbit models. Using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot, the early inflammatory reactions in the EBC group were shown to be lower than in the BC group, and were close to the autologous dura mater group. Histological observations and western blot revealed more collagen fibers evenly distributed on the outer side of EBC membranes than in the BC and unpatched groups, and fewer brain tissue adhesions and epidural scars were found in the EBC group. Compared with common BC membrane, the EBC membrane had better biophysical properties and biocompatibility. It is expected to be a suitable alternative material for the repair of damaged dura mater.

Notoginsenoside R1-Induced Neuronal Repair in Models of Alzheimer Disease Is Associated With an Alteration in Neuronal Hyperexcitability, Which Is Regulated by Nav.

Alzheimer disease is characterized by a progressive cognitive deficit and may be associated with an aberrant hyperexcitability of the neuronal network. Notoginsenoside R1 (R1), a major activity ingredient from Panax notoginseng, has demonstrated favorable changes in neuronal plasticity and induced neuroprotective effects in brain injuries, resulting from various disorders, however, the underlying mechanisms are still not well understood. In the present study, we aimed to explore the possible neuroprotective effects induced by R1 in a mouse model of AD and the mechanisms underlying these effects. Treatment with R1 significantly improved learning and memory functions and redressed neuronal hyperexcitability in amyloid precursor protein/presenilin-1 mice by altering the numbers and/or distribution of the members of voltage-gated sodium channels (Nav). Moreover, we determined whether R1 contributed to the regulation of neuronal excitability in Aß-42-injured cells. Results of our study demonstrated that treatment with R1 rescued Aß1-42-induced injured neurons by increasing cell viability. R1-induced alleviation in neuronal hyperexcitability might be associated with reduced Navß2 cleavage, which partially reversed the abnormal distribution of Nav1.1α. These results suggested that R1 played a vital role in the recovery of Aß1-42-induced neuronal injury and hyperexcitability, which is regulated by Nav proteins. Therefore, R1 may be a promising candidate in the treatment of AD.

Large-cohort comparison between three-dimensional time-of-flight magnetic resonance and rotational digital subtraction angiographies in intracranial aneurysm detection.

BACKGROUND AND PURPOSE: The value of MR angiography varies in diagnosis of intracranial aneurysms due to the difference of equipment and imaging technique. This study was to compare the effectiveness of 3-dimensional time-of-flight MR angiography at 3 T and rotational digital subtraction angiography, both with volume rendering (VR), in detecting intracranial aneurysms. METHODS: One hundred thirty-eight patients with suspected or known aneurysms and other cerebral vascular diseases detected by MR angiography underwent digital subtraction angiography examinations. Postprocessing techniques, including VR and the single artery highlighting method, were performed by a 3-dimensional specialist. The VR-digital subtraction angiography was obtained as the gold standard. RESULTS: The rotational digital subtraction angiography and VR-digital subtraction angiography revealed 146 aneurysms in 122 patients and no aneurysms in 16 patients. Of the 276 vessels examined, 136 vessels had 146 aneurysms and 140 vessels had none. Per vessel and per aneurysm sensitivities were 100%, whereas the per vessel accuracy ranged from 97.5% to 98.6% and the per aneurysm accuracy ranged from 95.1% to 97.0%. CONCLUSIONS: VR 3-dimensional time-of-flight MR angiography at 3 T has excellent sensitivity, accuracy, and correlation with VR-digital subtraction angiography and is comparable to catheter cerebral angiography for the evaluation of patients with intracranial aneurysms who tolerate MR angiography well.

Clinical characterization of comatose patients with cervical spine injury and traumatic brain injury.

BACKGROUND: Reports on the risk factors for combined craniocervical spine injury in comatose patients are rare. The incidence of concomitant cervical injury in comatose patients with traumatic brain injury (TBI) was determined herein. METHODS: One thousand twenty-six comatose patients with TBI were examined. The clinical characteristics of combined craniocervical trauma were documented, including type and location of cervical injury, occurrence of hypotension, and dyspnea. RESULTS: Seventy-one patients (6.92%) sustained cervical spine injury. The most common injury region included the upper cervical segments, demonstrated in 37 (52.11%) of 71 patients. Of the 71 patients who sustained combined craniocervical spine injury, 42 (59.15%) had hypotension, including 26 (36.62%) with dyspnea. With regard to the association between the severity of TBI and the incidence of the cervical injury, a significant difference was apparent between patients with an initial Glasgow Coma Scale (GCS) score of 3-5 and those with an initial GCS score of 9-12 (11.62% compared with 4.03%, p < 0.01). Regarding the relationship between the mechanism of injury and the occurrence of cervical spine injury, cervical spine injury was associated at a significantly higher incidence with motorcycle accident-related head trauma as compared with non motorcycle accident-related trauma (10.32% vs. 4.68%, p < 0.01). CONCLUSION: Patients who sustained TBI as a result of motorcycle accidents and those exhibiting a lower GCS score are at the highest risk for concomitant cervical spine injury.

Glial implications in transplantation therapy of spinal cord injury.

Spinal cord injuries are damages that result in complete or partial loss of sensation and/or mobility and affect the life qualities of many patients. Their pathophysiology includes primary and secondary processes, which are related with the activation of astrocytes and microgliacytes and the degeneration of oligodendrocytes. Although transplantation of embryonic stem cells or neural progenitor cells is an attractive strategy for repair of the injured central nervous system (CNS), transplantation of these cells alone for acute spinal cord injuries has not resulted in robust axon regeneration beyond the injury sites. This may be due to the progenitor cells differentiating to the cell types that support axon growth poorly and/or their inability to modify the inhibitory environment of adult CNS after injury. Recent studies indicate that transplantation of glial progenitor cells has exhibited beneficial effects on the recovery and promising future for the therapy strategy of spinal cord injury. In this review, we summarized the data from recent literature regarding glial implications in transplantation therapy of spinal cord injury.

Risk factors related to hospital mortality in patients with isolated traumatic acute subdural haematoma: analysis of 308 patients undergone surgery.

BACKGROUND: Acute subdural haematoma (ASDH) is a common traumatic brain injury with a relatively high mortality rate. However, few studies have examined the factors predicting the outcome of isolated traumatic ASDH. This clinical study examined the hospital mortality and analyzed the risk factors for mortality in patients treated surgically for isolated traumatic ASDH. METHODS: We collected 308 consecutive patients who underwent neurosurgery for isolated traumatic ASDH between January 1999 and December 2007 and used multivariate Logistic regression analysis to evaluate the influence of 11 clinical variables on hospital mortality. RESULTS: The overall hospital mortality was 21.75% (67/308). Age (OR = 1.807), preoperative Glasgow Coma Score (OR = 0.316), brain herniation (OR = 2.181) and the time from trauma to decompression (OR = 1.815) were independent predictors of death, while no independent association was observed between hospital mortality and haematoma volume, midline shift, acute brain swelling or brain herniation duration, although these variables were correlated with hospital mortality in univariate analyses. CONCLUSIONS: This study identified the risk factors for hospital mortality in patients who underwent surgical treatment for isolated traumatic ASDH. An increased risk of death occurs in patients who are over 50 years of age and have lower preoperative Glasgow Coma Scores, the presence of brain herniation and a long interval between trauma and decompression. The findings should help clinicians determine management criteria and improve survival.

Regulation of tNOX expression through the ROS-p53-POU3F2 axis contributes to cellular responses against oxaliplatin in human colon cancer cells.

BACKGROUND: Oxaliplatin belongs to the platinum-based drug family and has shown promise in treating cancer by binding to DNA to induce cytotoxicity. However, individual patients show diverse therapeutic responses toward oxaliplatin due to yet-unknown underlying mechanisms. We recently established that oxaliplatin also exert its anti-cancer activity in gastric cancer cell lines by targeting tumor-associated NADH oxidase (tNOX), attenuate NAD+ generation and reduce NAD+-dependent sirtuin 1 (SIRT1) deacetylase activity, which in turn enhances p53 acetylation and apoptosis. METHODS: In this study, differential cellular outcomes in response to oxaliplatin exposure of p53-wild-type versus p53-null HCT116 human colon cancer cells were examined. Cell growth profile was determined by cell impedance measurements and apoptosis was analyzed by flow cytometry. The engagement between oxaliplatin and tNOX protein was studied by cellular thermal shift assay. Furthermore, western blot analysis revealed that p53 was important in regulating tNOX expression in these cell lines. RESULTS: In p53-wild-type cells, we found that oxaliplatin inhibited cell growth by inducing apoptosis and concurrently down-regulating tNOX at both the transcriptional and translational levels. In p53-null cells, in contrast, oxaliplatin moderately up-regulated tNOX expression and yielded no apoptosis and much less cytotoxicity. Further experiments revealed that in p53-wild-type cells, oxaliplatin enhanced ROS generation and p53 transcriptional activation, leading to down-regulation of the transcriptional factor, POU3F2, which enhances the expression of tNOX. Moreover, the addition of a ROS scavenger reversed the p53 activation, POU3F2 down-regulation, and apoptosis induced by oxaliplatin in p53-wild-type cells. In the p53-null line, on the other hand, oxaliplatin treatment triggered less ROS generation and no p53 protein, such that POU3F2 and tNOX were not down-regulated and oxaliplatin-mediated cytotoxicity was attenuated. CONCLUSION: Our results show that oxaliplatin mediates differential cellular responses in colon cancer cells depending on their p53 status, and demonstrate that the ROS-p53 axis is important for regulating POU3F2 and its downstream target, tNOX. Notably, the depletion of tNOX sensitizes p53-null cells to both spontaneous and oxaliplatin-induced apoptosis. Our work thus clearly shows a scenario in which targeting of tNOX may be a potential strategy for cancer therapy in a p53-inactivated system.