Serum amyloid A1 in combination with integrin αVß3 increases glioblastoma cells mobility and progression.

Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM-associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVß3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region-specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and ß3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy.

Comparing miniopen and minimally invasive transforaminal interbody fusion in single-level lumbar degeneration.

Degenerative diseases of the lumbar spine, which are common among elderly people, cause back pain and radicular symptoms and lead to a poor quality of life. Lumbar spinal fusion is a standardized and widely accepted surgical procedure used for treating degenerative lumbar diseases; however, the classical posterior approach used in this procedure is recognized to cause vascular and neurologic damage of the lumbar muscles. Various studies have suggested that using the minimally invasive transforaminal interbody fusion (TLIF) technique provides long-term clinical outcomes comparable to those of open TLIF approaches in selected patients. In this study, we compared the perioperative and short-term advantages of miniopen, MI, and open TLIF. Compared with open TLIF, MI-TLIF and miniopen TLIF were associated with less blood loss, shorter hospital stays, and longer operative times; however, following the use of these procedures, no difference in quality of life was measured at 6 months or 1 year. Whether miniopen TLIF or MI-TLIF can replace traditional TLIF as the surgery of choice for treating degenerative lumbar deformity remains unclear, and additional studies are required for validating the safety and efficiency of these procedures.

Reverse Lhermitte's phenomenon provoked by cervical cord compression.

PURPOSE: Lhermitte's phenomenon (LP) is a rare manifestation, which is defined when a sudden electric-shock sensation transmitted down the spine induced by neck flexion; however, the reverse LP is defined when symptoms are induced by neck extension, not flexion. Because reports of LP are limited in the Taiwan literature, we report this case. CASE REPORT: A 74-year-old woman presented to our emergency department with sudden onset of right neck pain when extending the neck. The pain mimicked an electric shock and radiated to the left shoulder. Imaging showed spondylosis and spondylolisthesis without any spinal canal stenosis. A neck collar was recommended, and the strange phenomenon did not recur over the following year. However, long-term follow-up and aggressive workup are recommended to rule in or rule out the possibility of multiple sclerosis in the future. CONCLUSION: Although LP represents spinal demyelination disorders, reverse LP is induced by extrinsic compression of the cervical cord, and neck collar immobilization rather than intravenous or oral medication is recommended.

Early enteral nutrition and clinical outcomes of severe traumatic brain injury patients in acute stage: a multi-center cohort study.

Guidelines for patients with severe traumatic brain injury (sTBI) published in 2007 recommend providing early nutrition after trauma. Early enteral nutrition (EN) started within 48 h post-injury reduces clinical malnutrition, prevents bacterial translocation from the gastrointestinal tract, and improves outcome in sTBI patients sustaining hypermetabolism and hypercatabolism. The aim of this study was to examine the effect of early EN support on survival rate, Glasgow Coma Scale (GCS) score, and clinical outcome of sTBI patients. Medical records of sTBI patients with GCS scores 4-8 were recruited from 18 hospitals in Taiwan, excluding patients with GCS scores ≤3. During 2002-2010, data from 145 EN patients receiving appropriate calories and nutrients within 48 h post-trauma were collected and compared with 152 non-EN controls matched for gender, age, body weight, initial GCS score, and operative status. The EN patients had a greater survival rate and GCS score on the 7th day in the intensive care unit (ICU), and a better outcome at 1 month post-injury. After adjusting for age, gender, initial GCS score, and recruitment period, the non-EN patients had a hazard ratio of 14.63 (95% CI 8.58-24.91) compared with EN patients. The GCS score during the first 7 ICU days was significantly improved among EN patients with GCS scores of 6-8 compared with EN patients with GCS scores of 4-5 and non-EN patients with GCS scores of 6-8. This finding demonstrates that EN within 48 h post-injury is associated with better survival, GCS recovery, and outcome among sTBI patients, particularly in those with a GCS score of 6-8.

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke.

AIM: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. METHODS: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. RESULTS: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 levels during heatstroke. CONCLUSION: Our results suggest that systemic delivery of kynurenic acid may attenuate multiorgan dysfunction in rats after heatstroke.

Inhibition of Nodal suppresses angiogenesis and growth of human gliomas.

Angiogenesis is the hallmark of malignant gliomas positively correlated with the vascular endothelial growth factor (VEGF) expression. We previously reported that expression levels of Nodal, a member of transforming growth factor-ß super family, correlate with the malignant invasive behavior of human glioma cells. In this study, we show that knockdown of Nodal suppresses glioma angiogenesis by inhibition of VEGF. In human primary glioma specimens, expression of Nodal positively correlates with WHO glioma tumor grades and expression of VEGF in the corresponding glioma specimens. In human U87MG glioma cells, knockdown of endogenous Nodal by RNA interference (RNAi) significantly decreases colony formation and secretion of VEGF. In vivo, cellular depletion of Nodal in U87MG inhibited brain glioma growth and prolonged the survival of mice with U87MG/shNodal glioma compared with controls. Inhibition of Nodal suppressed tumor vessel growth in U87MG gliomas. Using Nodal inhibitor (SB431542), silencing Nodal, or overexpressing Nodal in the U87MG, GBM8401, and GBM glioma cells, our further experiments revealed that Nodal-induced VEGF expression might, at least in part, mediate through the ERK1/2-HIF-1α-mediated signaling pathway. Taken together, our data revealed that alteration of Nodal expression in glioma cells resulted in changes to VEGF secretion, and subsequent colony formation, in vivo tumor growth, and angiogenesis, all of which are consistent with the regulation of VEGF through the ERK1/2-HIF-1α-mediated signaling, suggesting that Nodal may serve as a potential therapeutic target for the treatment of human gliomas.

Osteopontin expression is a valuable marker for prediction of short-term recurrence in WHO grade I benign meningiomas.

Prediction of recurrence remains a challenge in histopathological benign/grade I tumors. Osteopontin (OPN) plays important roles in tumorigenesis, invasion, and metastasis of several human cancers. In this study, we investigated OPN protein expression by evaluating the differences between recurrent and non-recurrent histologically benign meningiomas. Thirty-two patients were enrolled, and 23 benign non-recurrent meningiomas and 9 benign recurrent meningiomas were followed for a mean of 34 months after complete surgical resection (Simpson grades I and II). Cytoplasmic OPN staining was evaluated by means of immunohistochemistry (IHC) score and by use of the Allred-8-unit system. We examined clinical biological data, their relationship with tumor recurrence, and the expression of OPN. Our results showed that meningioma recurrence correlated significantly with OPN IHC score (P = 0.001). An OPN Allred score between 0 and 3 was associated with a recurrence-free time of more than 25 months. In comparison, an OPN Allred score from 4 to 8 was indicative of a shorter average recurrence-free time. We concluded that OPN IHC score may play a role in prediction of the recurrence of the grade I meningiomas. Moreover, determination of the OPN Allred score is a reliable, quantitative tool for predicting recurrence-free time in benign meningioma patients.

Hyaluronic acid inhibits the glial scar formation after brain damage with tissue loss in rats.

BACKGROUND: Brain tissue scarring (gliosis) was believed to be the major cause of epileptic focus after brain injury, and prevention of scarring could reduce the incidence of seizure. We tried the HA coating onto the cortical brain defect of Spraque-Dawley rats to reduce the marginal glial scarring. METHODS: A 4 x 2 x 2 mm(3) cortical defect was created in the brain of Spraque-Dawley rats. Three percent HA gel was coated onto the lesion for the experimental groups and normal saline solutions for the control groups. The brain was retrieved 4, 8, and 12 weeks after treatment. The brains were then sectioned and processed for H&E and GFAP staining, and the thickness of the scarring and the number of GFAP+ cells were analyzed. RESULTS: The thickness of cutting marginal gliosis was significantly decreased in the HA groups. The 12-week HA group showed the smallest thickness of gliosis, whereas the 12-week control group exhibited the largest thickness of gliosis. The significant difference in the thickness of gliosis was also noted between the HA and the control groups 8 weeks after treatment. The number of GFAP+ cells was also significantly decreased in the HA groups when compared to the respective control group 4, 8, and 12 weeks after the surgery. CONCLUSION: The results support the hypothesis that HA inhibits glial scarring not only by decreasing the thickness of gliosis but also by reducing the number of the glial cells. Furthermore, our results suggest that HA might be used to reduce glial scar formation in central nervous system surgery, which subsequently prevents the post-operation or posttraumatic seizure incidence.

Biochemical alteration in cerebrospinal fluid precedes behavioral deficits in Parkinsonian rats induced by 6-hydroxydopamine.

BACKGROUND: Parkinson's disease, affecting at least 1% of population older than 65 years, is the most common neurodegenerative movement disorder. Up to now, no evidence has demonstrated that biochemical changes in CSF occur preceding the onset of Parkinson's symptoms. In this study, we tested the hypothesis that biochemical changes in CSF precede behavioral deficits in Parkinsonian animals. METHODS: We infused different doses of 6-OHDA into the MFB of rats bilaterally and examined the animals' movement behaviors, biochemical alterations in CSF, and dopaminergic neuronal number in the SNpc 1 week later. RESULTS: Our results indicated that animals with over 70% dopaminergic neuronal loss in the SNpc exhibited behavioral bradykinesia and rigidity, and a decrease of HVA in CSF. In contrast, animals with about 42% dopaminergic neuronal loss in the SNpc showed normal movement behaviors, but displayed a drastic decline of HVA in CSF. Furthermore, the number of dopaminergic neurons in the SNpc was positively correlated with the HVA level in CSF. CONCLUSIONS: Our findings demonstrate that biochemical alteration in CSF foreruns behavioral deficits and the HVA level in CSF is positively correlated with the number of dopaminergic neurons in the SNpc of Parkinsonian rats induced by 6-OHDA. Our results strongly suggest that additional studies are needed to evaluate usefulness of monitoring the HVA level in CSF for early detection of the loss of dopaminergic neurons in the SNpc that precedes the onset of Parkinsonian symptoms in humans.

Traumatic internal carotid artery pseudoaneurysm mimicking sphenoid sinus tumor.

Massive epistaxis following blunt craniofacial trauma should alert clinicians to possible traumatic internal carotid artery (ICA) aneurysm. This article describes a case of a 46-year-old female patient with traumatic ICA pseudoaneurysm presenting similar to a sphenoid sinus mass lesion. Massive bleeding occurred during the endoscopic procedure. Brain angiography revealed two lobulated ICA pseudoaneurysms over a cavernous segment. The patient successfully underwent endovascular stent assisted coil embolization. Timely diagnosis and treatment of the ICA psuedoaneurysm produced a favourable outcome.

Intracranial pial arteriovenous fistulas with single-vein drainage. Report of three cases and review of the literature.

Intracranial pial arteriovenous fistulas (AVFs) are rare vascular lesions, of which fewer than 90 cases have been reported in the literature. They are composed of one or more arterial feeding vessels and a single draining vein that usually result in a huge varix. Because of the high-flow shunting, a poor prognosis is associated with conservative treatment. Surgical or endovascular treatment also poses various challenges. The authors present the cases of three patients in whom N-butyl-2-cyanoacrylate-assisted embolization was performed. Outcome in all three cases was good. The necessity of staged procedures to obliterate the AVF is also discussed.