Research Advances in Idiopathic Intracranial Hypertention / 中国医学科学院学报

Idiopathic intracranial hypertension,also known as pseudotumor cerebri,is a syndrome characterized by raised intracranial pressure of unknown cause.These patients present normal neuroimaging and cerebrospinal fluid analysis while increased intracranial pressure and associated symptoms and signs.Delay of treatment can cause severe visual impairment.There are some new understandings of this disease,and we will review the pathogenesis,diagnosis,and treatment of idiopathic intracranial hypertension.

Advancement in Diagnosis and Treatment of Elevated Intracranial Pressure in Patients with Cryptococcal Meningitis / 中国医学科学院学报

Cryptococcal meningitis(CM)is often seen in immunocompromised patients and has become a global health concern. Elevated intracranial pressure(ICP)is a common complication of CM and often leads to poor prognosis. Monitoring and management of ICP is an important task in CM patients. Invasive intervention is often needed for the elevated ICP in CM patients due to the pathophysiological features of this condition. This article review the recent progress in the diagnosis and treatment of elevated ICP in CM patients.

Treatment of blood disease with chronic subdural hematoma / 基础医学与临床

Objective To understand the characteristics of patients with hematological illness and chronic subdural hematoma.,and the effect of blood disease on the treatment of chronic subdural hematoma. To guide the treatment of patients who both with hematological illness and chronic subdural hematoma. Methods Through a retrospective study of the cases of chronic subdural hematoma from January 1, 2000 to June 1, 2017 in Peking Union Medical College Hospital, the following items were investigated. 1).According to whether or not they were associated with blood disorders, the collected cases were divided into the blood disorders group and the non-blood disorders group. And the clinic data of the sex composition, average ages, treatment effect and mortality were compared. 2). Ac-cording to the treatment, the cases with blood disease were divided into the surgical group and the conservative group. And the treatment effect and mortality were compared. Results A total of 433 patients with chronic subdural hematoma were included in this study, including 35 patients associated with hematological illness. 1) Compared to the controls group, the patients group was younger( P＜0.01) ;the male ratio was lower ( P＜0.01) ; the treatment effect was lower( P＜0.001) and the mortality was higher( P＜0.001) . 2) Within the patients with hematological illness, the surgical group had the better treatment effect(78.9% vs 31.3%,P＜0.01) and the lower mortality (15.8% vs 50.0%,P＜0.05). Conclusions 1)The hematological illness group is younger and the male ratio is lower than the non-hematological illness group; 2) The hematological illness is a risk factor for the treatment of chronic subdural hematoma; 3) The patients who both with the hematological illness and the chronic subdural he-matoma should be treated by surgery.

Protection of Nerve Injury with Exosome Extracted from Mesenchymal Stem Cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism.</p><p><b>METHODS</b>Characteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 μmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 μmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 μmol/L TrkB).</p><p><b>RESULTS</b>Exosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01).</p><p><b>CONCLUSION</b>Exosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.</p>

Diagnosis and Treatment of Pituitary Carcinoma / 中国医学科学院学报

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

Advances in the pathogenesis and treatment of neurosurgical emergency with coagulation disorders / 中国医学科学院学报

Neurosurgical emergencies including intracranial hemorrhage and head trauma have high mortality and morbidity rates and meanwhile are often accompanied with coagulation disorders. On one hand, coagulation disorder follows traumatic brain injury;on the other hand, the increasing use of anticoagulant and antiplatelet treatment for cardiovascular diseases increases the risk of death among patients with brain trauma or bleeding. Once the intracranial pressure increases, such patients need emergency surgical intervention, but coagulation disorder is a relative contraindication. This article reviews the pathogenesis and treatment of coagulation disorders in patients with neurosurgical emergency. It also analyzes clinical monitoring indices for such patients and their variations and summarizes the strategies and measures of perioperative management.

Osmotic demyelination syndrome in patients with hyponatremia caused by neurologic disorders / 中国医学科学院学报

Hyponatremia is relatively common in patients with neurologic disorders, while its diagnosis and treatment remain controversial. Osmotic demyelination syndrome (ODS) has shown to be closely associated with hyponatremia. ODS patients often present as central pontine myelinolysis, extrapontine myelinolysis, or both. This article reviews the clinical manifestations, pathogenesis, and risk factors of ODS in patients with hyponatremia caused by neurologic disorders.

Management of pulmonary thromboembolism in post-operative neurosurgical patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the diagnosis and treatment of pulmonary thromboembolism (PTE) in post-operative neurosurgical patients.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 7 patients who experienced pulmonary thromboembolism after neurosurgical operations in our department from October 2009 to March 2010.</p><p><b>RESULTS</b>Of these 7 patients, 6 were confirmed with computed tomographic pulmonary angiography (CTPA) and 1 was diagnosed according to the clinical manifestations and other diagnostic examinations. All the patients were treated initially with low-dose heparin or low-molecular-weight heparin and then with warfarin. Two patients were implanted with permanent inferior vena cava filters before anticoagulation. One received anticoagulant therapy and died of respiratory failure due to pulmonary embolism on the fourth post-operative day. Six patients were discharged after significant improvement.</p><p><b>CONCLUSIONS</b>Many risk factors may cause PTE peri-operatively. Post-operative CTPA may be indicated. Anticoagulation and other management strategies may be applied to improve the outcome.</p>

Preparation of brain targeted immunoliposomes / 药学学报

To prepare a kind of effective non-viral transduction vector, which can deliver exogenous gene into the brain, this vector can be injected through vein system and has the ability to penetrate blood brain barrier. Several groups of materials proportion, type of oil phase, water-oil ratio, phosphatides-cholesterol ratio, temperature of steaming, ultrasonic temperature and time were compared for optimization. Well-constructed immunoliposomes encapsuling LacZ gene were infused into rats through tail vein. 48 h after injection, expression product beta-galactosidase of LacZ gene was detected by histochemistry staining to convince the validity of immunoliposomes as non-viral vectors. The best proportion of synthesis immunoliposomes is as following: phosphatides-cholesterol ratio is 1:1, lipids/drug is 100:1, the type of oil phrase is dichloromethane, oil-water ratio is 4:1, temperature of steaming is 30 degrees C, ultrasonic temperature and time is 10 degrees C and 5 min. At last, 10% trehalose was added as a stabilizer. The entrapment rate is 87.24% and antibody coupling rate is 69%. When immunoliposomes were infused into rats, the expression of LacZ gene could be observed in the brain and periphery organs. Through the best proportion of materials, gene delivering immunoliposomes had been synthesized successfully. This non-viral vector can deliver exogenous gene penetrating blood brain barrier and express in the brain, and will be well-used in the field of gene therapy of cerebral diseases.

Ferumoxide labeled Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells and its in vivo tracing in the brains of Macaca Fascicularis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis.</p><p><b>METHODS</b>The hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining.</p><p><b>RESULTS</b>The marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods.</p><p><b>CONCLUSIONS</b>Ferumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.</p>

In vivo tracking of bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide after cerebral ischemia in rats by magnetic resonance imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility of in vivo tracking of bone marrow mesenchymal stem cells (BMSCs) labeled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) in rats after cerebral ischemia, and to analyze the influence of stem cell therapy on the volume of cerebral infarction.</p><p><b>METHODS</b>The samples of rat bone marrow were collected. BMSCs separated by density gradient centrifugation were cultivated and harvested until the third passage. BMSCs were labeled with SPIO, which was mixed with poly-L-lysine. The labeling efficiency was evaluated by Prussian blue staining. Transient middle cerebral arterial occlusion (MCAO) was performed successfully in 18 adult Sprague-Dawley rats that scored from 6 to 12 by the modified neurological severity test. The 18 rats were then randomly divided into group A, B, and C, with 6 rats in each group and Group C was regarded as control group. BMSCs were injected into the contralateral cortex of ischemia in group A, ipsilateral corpora striata in group B, while D-Hank's solution was injected into ipsilateral corpora striata (group C) 24 hours after MCAO. MRI was performed 1 day after MCAO, 1 day and 14 days after transplantation. The volume of infarcted brain tissue was measured and analyzed. Prussian blue staining of brain tissues was performed to identify the migration of BMSCs.</p><p><b>RESULTS</b>The labeling efficiency of BMSCs with SPIO was 96%. The transplanted BMSCs migrated to the ischemic hemisphere along the corpus callosum and to the border of the infarction, which was confirmed by MRI and Prussian blue staining. The changes of infarction volume were not significantly different among these three groups.</p><p><b>CONCLUSIONS</b>MRI is feasible for in vivo tracking of BMSCs labeled with SPIO in rats. The stem cell therapy may not be able to affect the volume of cerebral infarction.</p>

Neuronavigation guidance for motor cortex stimulation in resection of gliomas involving the precentral gyrus / 中华显微外科杂志

Objective To explore surgical treatment of gliomas involving the motor eloquent area. Methods Twelve cases of gliomas involving precentral gyrus were underwent awake surgery procedures assis- ted with neuronavigation and brain functional mapping by cortical electrical stimulation.Results Eleven ca- ses acquired accurate location of both lesions and eloquent areas by neuronavigation and direct cortical stimula- tion.7 cases of motor cortices and 2 cases of motor speech centers were confirmed during the operation.Re- section,verified by postoperative MRI,was total in 8 cases (66.7%) and subtotal in 4 patients.Histological examination revealed an infiltrative glioma in all cases (8 low grade astrocytomas,2 high grade astrocytomas and 2 glioblastoma).Four patients had no postoperative deficit,while the other 8 patients were impaired, with,in all cases except one,complete recovery in 7 days to one month.Conclusion Direct cortical elec- trical stimulations and awake surgery offer a reliable,precise and safe method,allowing functional mapping es- pecially useful in case of infiltrative cerebral tumors in eloquent areas.This technique allows improvement in the quality of tumoral resection and concurrently a minimization of the risk of definitive postoperative neurologi- cal deficit.