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Objective: To explore the clinical characteristics, diagnostic strategies and surgical techniques of hemangioblastoma (HB) in medulla oblongata., Methods: The clinical and radiological characteristics, therapeutic processes and outcomes of 12 HB cases treated at our department from 2002 to 2012 were studied by retrospective analysis., Results: Headache, somatic numbness and limb muscle weakness were the major symptoms of oblongata HB. Magnetic resonance imaging before surgery revealed a total of 12 single tumors. Among these tumors, upper (n = 1), middle (n = 7) and lower (n = 4) parts of medulla oblongata were involved. The locations were surface (n = 9) and intramedullary (n = 3). Three tumors had cyst. Digital subtraction angiography (DSA) was performed on 5 cases and it revealed that the main blood supply arteries of tumors were branches of posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA).One case underwent pre-surgical embolism during angiography. Eleven tumors were totally resected and 1 was fulgurized.Symptoms improved (n = 8) and worsened (n = 2). And two patients died. All survivors were followed up for 3 months to 10 years and had a McCormick functional grading of I-II.One case relapsed 7 year later., Conclusion: For Cystic HB, small or medium sized substantial HB in middle and lower part of oblongata, surgical removal is often safe and symptoms may be lessened.It can be used as a first-line treatment. For large ( ≥ 3 cm) substantial HB or HB in upper part of oblongata, serious postoperative complications such as respiratory failure, neurogenic pulmonary edema or acute obstructive hydrocephalus may occur. Thus surgical resection should be prudently considered and possible consequences thoroughly discussed with the patients.

Objective: To investigate the microsurgical strategies of glioma located in lateral fissure area., Methods: The clinical data of 123 patients with glioma located in lateral fissure area confirmed by pathology, 76 males and 47 females, aged 46.2 (4-75), were retrospectively analyzed. The optimal surgical approach and comprehensive therapeutic strategies were selected according to the imaging features and pathological properties of tumors. Resections were performed by the pterion approach in all cases to remove the tumors, navigational orientation was used in 17 cases, and supervision by B mode ultrasonography was used in 12 cases. The branches of middle cerebral artery and fissure vein were protected carefully. The patients with tumors above grade U, confirmed pathologically after resection, underwent chemotherapy ( teniposide + semustine or temozolomide) and radiotherapy that was designated individually according to the pathological grade and distribution of the tumors. Follow-up was conducted by telephone, mail or outpatient department visit on 102 of the 133 patients (82.9%)., Results: 82 patients (66.7%) underwent total resection, 18 (14.6%) underwent subtotal resection, 16 (13.0%) underwent major resection, and 7 (5.7%) underwent partial resection. Postoperatively cerebral vasospasm in 8 cases, brief aphasia and reaction clumsily in 4 cases, muscle strength decline in 3 cases, and epilepsy in 1 case, these patients were submitted to symptomatic treatment with progressive improvement of the above-mentioned signs and symptoms. One patient died of malignant intracranial hypertension. The follow-up showed that 97 patients survived over 1 year, the 5-year survival rate was 25.6%, and the average survival time was 21.7 months., Conclusion: The lateral fissure area glioma can be treated through proficient microsurgical technique after the anatomic training. It is the key in the surgery on the lateral fissure glioma to protect the main branches of middle cerebral artery, trunk of middle cerebral vein, and important brain functional areas.

Objective: To compare the effects of treatment of spasmodic torticollis (ST) by neurovascular decompression, myotomy, and botulinum toxin type A and to investigate the mechanism of ST., Methods: Nine ST patients who failed to respond to other conservative treatment methods underwent neurovascular decompression of accessory nerve. The effect of decompression was compared with that by botulinum toxin in 22 patients and that by myotomy in 13 patients., Results: The symptoms and signs were improved to a certain degree by botulinum toxin treatment at first, but recurred and gradually worsened in several months. None of the 22 patients had reached a real cure by botulinum toxin type A treatment. Four of 13 patients undergoing myotomy improved a lot in the symptoms and 9 improved only a bit. However, weakness in neck movement was found in all patients after myotomy. Neurovascular decompression was performed on 9 patients, 5 of which had botulinum toxin treatment and 1 had undergone myotomy, and found that all of them had severe vascular compression in the accessory nerve. Obvious alleviation of symptoms was achieved 2 - 14 days after the operation in 8 patients, and 3 months later in 1 patient. All of the 9 patients resumed their nonenal work and life 6 months after the operation. No complication, such as nerve damage, infection, hemorrhage, leakage of cerebrospinal fluid, and weakness of neck, was found., Conclusions: Neurovascular compression may be the most important cause of ST. Microneurovascular decompression is effective for some patients. However, it is still difficult to judge its indication.

Objective: To explore the efficacy and strategy of transarterial embolization of dural carotid-cavernous fistulas., Methods: The clinical data of 19 patients with dural carotid-cavernous fistulas treated by transarterial embolization, including clinical presentations and patterns of angioarchitecture were retrospectively analyzed. Follow-up was conducted for 7 months to 4 years., Results: Clinical cure was achieved in 15 cases, significant improvement of symptoms in 3 cases, and failure in 1 case. Complete angiographic obliteration was documented in 12 patients (63%) right after the embolization. Residual shunting was left in 6 patients, and disappeared in 5 cases one month to half a year later by manual compression of the carotid artery. The patient on which transarterial embolization failed received embolization via the bilateral cavernous later, and clinical cure was achieved. Headache and vomiting were the most common symptoms after embolization. There was no permanent procedure-related morbidity. No recurrence was seen during the follow-up., Conclusion: Transarterial embolization is a safe, efficient and economical method for part of the cavernous sinus dural arteriovenous fistula patients.

Objective: To compare the regional specificity in proliferation capacity of neural stem cells derived from hippocampus and epithalamus: study with rats., Methods: Neural stem cells (NSCs) were separated mechanically from the hippocampus and the epithalamus of an embryo of SD rat respectively and cultured in serum-free medium to observe the growth status dynamically and their in vitro growth curves were drawn. Single cell clones were established and identified by immunofluorescence staining. The surface morphology of the clone balls were observed by using scanning electron microscope. The ultrastructure was observed by scanning electron microscopy. The 3D morphology was observed under a laser confocal microscope. NSCs were co-incubated with 5-bromodeoxyuridine (Brdu) and immunofluorescence staining was used to observe their in vitro proliferation potentials. Studies on., Results: The in vitro growth of the hippocampus-derived NSCs was basically the same as that of the epithalamus-derived NSCs, however, the culture fluid of the epithalamus-derived NSCs became yellowish 18 hours after the inoculation, significantly earlier than that of the hippocampus-derived NSCs. Showing a faster multiplication rate of the latter. Scanning electron microscopy showed that these two types of NSCs had a similar ultrastructural feature. Phase contrast microscopy and laser confocal microscopy showed similar form in the NSCs from two different sources. Co-incubation with found that the Brdu positive rate of the epithalamus-derived NSCs was 74.87%, significantly higher than that of the hippocampus-derived NSCs (63.07%, P < 0.05). The cell growth curves of the NSCs from both sources displayed the same multiplication trend, however, the NSC count of the epithalamus-derived NSCs at the 8th, 12th, 16th, 20th, and 24th days after culture were all higher than those of the corresponding hippocampus-derived NSCs at the same time-points (all P < 0.05)., Conclusion: Both embryonic hippocampus-derived and epithalamus-derived NSCs can be acquired by using mechanical separation and serum-free culture method. The two types of cells have a similar morphological structure and possess the in vitro multiplication capacity. However, the multiplication rate of the epithalamus-derived NSCs is higher than that of the hippocampus-derived NSCs.

Objective: To explore the protective effect of glial growth factor-2 (GGF2) on brain injury., Methods: Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP., Results: The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P < 0.05). The beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P < 0.05). The walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P < 0.05). The improvement in beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P < 0.05). The neuron number in the CA1 region in hippocampus of the treatment group was 102 +/- 11, significantly more than those of the vector control group and liposome group (67 +/- 8 and 58 +/- 9 respectively, both P < 0.01). Higher level of immunoreactivity with MBP was also detected in the cortex in the rats of the treatment group., Conclusion: Cationic liposome-mediated GGF2 gene therapy effectively promotes the recovery of brain injury.

Objective: To establish an animal model of chronic optic nerve injury which is suitable for experimental research., Methods: Dil, a tracer, was injected through the bone windows into the brain of 48 cats so as to mark the retinal ganglion cells (RGCs). Two weeks later the 48 cats were randomly divided into 6 equal groups. The normal group did not receive any other treatment. Other 8 cats underwent sham operation. Imitating the clinical pterional approach, a balloon was implanted into the place under the optic nerve and chiasm in the other 32 cats, then the volume of the balloons were increased by injecting contrast agent at different times to cause the optic nerve and chiasm compressed chronically for 1, 2, 4, or 6 weeks. Flash-visual evoked potential (F-VEP) was measured before operation and at the corresponding observation times in different groups. By the end of the experiment the cats were killed with the specimens of retina and optic nerve taken out to undergo light microscopy and electron microscopy to observe the pathological changes. Eight eyes were taken out from each group to calculate the number of RCGs 1, 2, 4, and 8 weeks after operation respectively., Results: Microscopy showed retina showed profound morphological changes 8 weeks after compression; Demyelination of optic nerve began to occur 2 weeks after compression and progressed later. Axonal degeneration was found 4 week after compression and became more significant 8 weeks later. Under electron microscopy, pathological changes of retina was found 4 weeks and more prominent 8 weeks after compression; Slight demyelination and disorganized of cytoskeleton in the optic nerve were shown 2 weeks after compression, and became more profound later; Myelin regeneration was found 8 weeks after compression. The number of RGCs was reduced significantly by 37% (293/465) since 8 weeks after compression. F-VEP recording showed an extension of latency and depression of amplitude 4 weeks after compression, and the changes were more significant 8 weeks later., Conclusion: An animal model of chronic optic nerve injury by compression has been established which is stable and well repeatable. The pathological changes of compressed optic nerve are aggravated gradually as the compression lasts and the volume increases. Degeneration of RGCs occurs secondarily and obviously later than the axonal degeneration.

Objective: To clone and identify expression pattern of the novel LNX gene, and characterize its molecular mechanism in all grades of human gliomas., Methods: From a fetal brain cDNA library, we isolated the novel human LNX gene. The expression pattern of LNX gene in 16 normal tissues was examined by MTC panel (Clontech). Microarray were adopted and hybridized with LNX probes to examine the expression of novel gene in gliomas. Northern hybridization was used for verifying expression of LNX gene in gliomas. Two-hybrid screen in yeast was used to identify human LNX interacting proteins. Pull-down assays and Co-immunoprecipitation were transfected in HEK293 cells according to the lipofectAMINE protocol., Results: We isolated a 3.7 kb cDNA containing an open reading frame (ORF) of 1,899 bp and a putative 632 amino acids protein, which was located on 4q12. cDNA microarray showed LNX was down-regulated in all 18 glioma samples and it was testified by Northern-blot. The MTC panel showed a ubiquitous expression pattern which highly expressed in adult brain, kidney and pancreas, while weak expression in heart, lung, etc. The two-hybrid screen in yeast revealed that LNX interacted with SKIP (Ski interacting protein) via PDZ domains. The co-immunoprecipation suggested that LNX interacted with SKIP in HEK293 cells and could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch., Conclusion: cDNA microarray technology is a powerful technique in screening and locking differentially expressed genes in gliomas, LNX was closely related to human gliomas and suggested playing an important role in gliomas by notch signal approach.

Objective: To construct a dually targeting gene therapy system for pituitary adenomas and investigate its effect., Methods: Promoter hGHp containing human growth hormone gene was obtained from human genome and cloned into the plasmid pcDNA3.1/His A with the promoter cut to construct the recombinant plasmid pcDNA3.1/His A-hGHp. HSV-TK gene was obtained from the plasmid pcDNA3.1/His A-TK and integrated into the plasmid pcDNA3.1/His A-hGHp to construct the recombinant plasmid pcDNA3.1/His A-hGHp-TK. A GE7 gene delivery system-mediated human growth hormone promoter controlled gene therapy system was constructed by adding the mixture of GE7-polylysine and HA20-polylysine into the DNA solution. Human growth hormone-secreting pituitary adenoma cells of the GH3 line, human myeloma cells of the U-2OS line, and human oophoroma cells of the HO8910PM line were cultured and transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK. Western blotting was used to examine the expression of PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK protein, MTT method was used to detect the cell survival rate. Another GH3, U-2OS, and HO8910PM cells were cultured and transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK and then ganciclovir (GCV) was added. MTT method was used to examine the cell survival rates. GH3 cells were injected subcutaneously into the right axilla of 200 SD nude rats loaded with human pituitary adenoma. Three weeks after the rats were randomly divided into 5 equal groups: PBS group in which PBS was injected into the tumor and GCV was injected peritoneally; GE7 group in which GE7-polylysine and HA20-polylysine were injected into the tumor and GCV was injected peritoneally; without TK group in which GE7-packaged pcDNA3.1/His A-hGHp was injected into the tumor and GCV was injected peritoneally; without GCV group in which GE7-packaged pcDNA3.1/His A-hGHp-TK was injected into the tumor and PBS was injected peritoneally; and treatment group in which GE7-packaged pcDNA3.1/His A-hGHp-TK was injected into the tumor and GCV was injected peritoneally. Peritoneal injection lasted 21 days for all groups. On the days 3, 7, 14, and 21 eight rats from each group were killed to measure the volume of tumor. The survival rate of the rest 8 rats was observed., Results: A dually targeting gene therapy system for pituitary adenoma was composed successfully. HSV-TK protein was expressed in the GH3 cells but not in the U-2OS and HO8910PM cells after transfection of GE7-packaged pcDNA3.1/HisA-hGHp-TK; and was expressed in the GH3 and HO8910PM cells but not in the U-2OS cells after transfection of GE7-packaged pcDNA3.1/HisA-TK. Transfection of GE7-packaged pcDNA3.1/HisA-hGHp-TK and addition of GCV significantly decreased the survival rate of the GH3 cells, but did not influence the survival rates of the U-2OS and HO8910PM cells. Transfection of GE7-packaged pcDNA3.1/HisA-TK and addition of GCV significantly decreased the survival rate of GH3 and HO8910PM cells but did not influence the survival of the U-2OS and HO8910PM cells. When the GH3 cells were transfected with GE7-packaged pcDNA3.1/HisA-hGHp-TK with the addition of GCV of the concentration of 4 mg/L the survival rate decreased to 10%, when the GCV concentration was raised to 8 mg/L the survival rate of the GH3 cells was < 5%. Three days after the beginning of treatment the tumor volume of different groups of rats increased at different degrees and the tumor was smallest in the treatment group in comparison with the other groups (all P < 0.05). Seven days after the beginning of treatment the tumor volume of the treatment group significantly decreased and the tumors of the other groups still increased (all P < 0.001). The survival time of the treatment group was over 120 days, significantly longer than those of the other groups (all about 40 days)., Conclusion: GE7 system-mediated hGHp controlled gene therapy system is hopeful to be the targeted therapeutic strategy for pituitary adenomas.

Objective: To screen differentially expressed genes in the development of human glioma and establish molecular classification of glioma preliminary based on gene expression using cDNA microarray., Methods: Brain specimens were obtained from 18 patients with glioma, 10 males and 8 females, aged 14 approximately 62 with an average age of 44.4. The total RNAs of these glioma specimens and 2 specimens of donated brain of normal adults were extracted. BioStarH140S microarray (including 8347 old genes and 5592 novel genes) were adopted and hybridized with probes which were prepared from the total RNAs. Differentially expressed genes between the normal tissues and glioma tissues were assayed after scanning cDNA microarray with ScanArray 4000. Northern hybridization, and in situ hybridization (ISH) were used to identify the functions of novel genes. Those differentially expressed genes were studied with Hierarchical method and molecular classification of glioma was preliminarily carried out., Results: Among the 13 939 target genes, there were 1200 (8.61%) differentially expressed genes and 395 (2.83%) novel genes. 348 genes were up-regulated and 852 genes were down-regulated in glioma. The results of bioinformatical analysis, Northern hybridization and ISH revealed that those novel genes were highly associated with glioma. There were multiple genes which were relevance to classification by Hierarchical method, such as MAP gene, cytoskeleton and matrix motility genes, etc. Molecular classification of glioma with Hierarchical cluster was in accordance with pathology and revealed internal essence in tumorigenesis and development., Conclusion: Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between two different kinds of tissues.