侵袭性脑膜瘤的影像学特征与手术策略

目的探讨侵袭性脑膜瘤的影像特征和手术治疗方法。方法回顾性分析56例侵袭性脑膜瘤患者的临床表现、影像学检查、病理结果及手术治疗情况等资料。结果56例侵袭性脑膜瘤在影像学上表现有颅骨的局部增生(18例),肿瘤侵蚀破坏颅骨(11例),硬脑膜"尾"征(27例),瘤-脑界面部分或完全消失(29例),肿瘤边界毛糙模糊、结节状或指状突出、伪足征(24例),肿瘤粘附或侵入静脉窦或海绵窦(9例),包绕大血管4例,瘤周明显水肿(39例)等。手术切除按Simpson标准分级,其中0级21例,Ⅰ级19例;Ⅱ级9例,Ⅲ级7例。术后随访0.5～8年,痊愈49例,轻度功能障碍7例。无死亡病例,复发4例。结论侵袭性脑膜瘤有较特殊的影像学特征,可为临床诊断和手术治疗提供参考。尽可能地行病灶根治性切除能有效地减少肿瘤的复发。

Alterations of intestinal mucosa structure and barrier function following traumatic brain injury in rats

AIM: Gastrointestinal dysfunction is a common complication in patients with traumatic brain injury (TBI). However, the effect of traumatic brain injury on intestinal mucosa has not been studied previously. The aim of the current study was to explore the alterations of intestinal mucosa morphology and barrier function, and to determine how rapidly the impairment of gut barrier function occurs and how long it persists following traumatic brain injury.METHODS: Male Wistar rats were randomly divided into six groups (6 rats each group) including controls without brain injury and traumatic brain injury groups at hours 3,12, 24, and 72, and on day 7. The intestinal mucosa structure was detected by histopathological examination and electron microscopy. Gut barrier dysfunction was evaluated by detecting serum endotoxin and intestinal permeability. The level of serum endotoxin and intestinal permeability was measured by using chromogenic limulus amebocyte lysate and lactulose/mannitol (L/M) ratio, respectively.RESULTS: After traumatic brain injury, the histopathological alterations of gut mucosa occurred rapidly as early as 3 hours and progressed to a serious state, including shedding of epithelial cells, fracture of villi, focal ulcer, fusion of adjacent villi, dilation of central chyle duct, mucosal atrophy,and vascular dilation, congestion and edema in the villous interstitium and lamina propria. Apoptosis of epithelial cells,fracture and sparseness of microvilli, loss of tight junction between enterocytes, damage of mitochondria and endoplasm, were found by electron microscopy. The villous height, crypt depth and surface area in jejunum decreased progressively with the time of brain injury. As compared with that of control group (183.7±41.8 EU/L), serum endotoxin level was signnificantly increased at 3, 12, and 24 hours following TBI (434.8±54.9 EU/L, 324.2±61.7 EU/L and 303.3±60.2 EU/L, respectively), and peaked at 72 hours (560.5±76.2 EU/L), then declined on day 7 (306.7±62.4 EU/L,P＜0.0L). Two peaks of serum endotoxin level were found at hours 3 and 72 following TBI. L/M ratio was also significantly higher in TBI groups than that in control group (control,0.0172±0.0009; 12 h, 0.0303±0.0013; 24 h, 0.0354±0.0025;72 h, 0.0736±0.0105; 7 d, 0.0588±0.0083; P＜0.01).CONCLUSION: Traumatic brain injury can induce significant damages of gut structure and impairment of barrier function which occur rapidly as early as 3 hours following brain injury and lasts for more than 7 days with marked mucosal atrophy.

Differentiation of Rat Neural Stem Cells and Its Relationship With Environment

Objective To explore the differentiation fates of rat neural stem cells (NSCs) in different environmental conditions. Methods NSCs derived from 16-day-old rat embryo were proliferated in vitro and implanted into the brain of rats with intra-cerebral hemorrhage. At the same time some NSCs were co-cultured in vitro with Schwann cells derived from newborn rats. MAP-2, GFAP and GalC (which are the specific markers of neural cells, astrocytes and oligodendrocytes respectively), BrdU and β-tubulin were detected by immunohistochemical and immunofluorescent methods. Results BrdU positive cells that were implanted into the brain dfstributed around the hemorrhagic area. The majority of them were GFAP positive astrocytes while a few of them were β-tubulin positive neural cells or GalC positive oligodendrocytes. After being co-cultured with Schwann cells in vitro, NSCs are predominately shown β-tubulin and MAP-2 positive, and only a minority of them were GFAP or GalC positive. Conclusions The hemorrhagic environment in vivo induces NSCs to differentiate mainly into astrocytes while co-culture with Schwann cells in vitro induce the majority of NSCs to differentiate into neural cells.

Levels of vasoactive intestinal peptide,cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction

AIM:To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.METHODS:Rat models of focal traumatic brain injury were established by impact insult method,and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3,12,24,72h,and d 7.Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously.The levels of vasoactive intestinal peptide (VIP) in plasma,calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VIP in jejunum.RESULTS:Gastric distension,delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12h and 72h, which peaked at postinjury 72h. As compared with that of control group (247.8±29.5ng/L), plasma VIP levels were significantly decreased at postinjury 3,12 and 24h (106.7±34.1ng/L, 148.7±22.8ng/L,132.8±21.6ng/L,respectively),but significantly increased at 72h (405.0±29.8ng/L) and markedly declined on d 7 (130.7±19.3ng/L).However,Plasma levels CCK and CGRP were significantly increased through 3h and 7d following TBI (126-691% increases),with the peak at 72 h.Compared with control (VIP, 13.6±1.4ng/g;CGRP,70.6±17.7ng/g);VIP and CGRP levels in jejunum were significantly increased at 3h after TBI (VIP,35.4±5.0ng/g;CGRP,103.8±22.1ng/g),and declined gradually at 12 h and 2d h (VIP,16.5±1.8ng/g,5.5±1.4ng/g;CGRP,34.9±9.7ng/g, 18.5±7.7ng/g),but were significantly increased again at 72 h (VIP, 48.7±9.5ng/g; CGRP,142.1±24.3ng/g),then declined in various degrees on d 7 (VIP, 3.8±1.1ng/g; CGRP, 102.5±18.1ng/g).The CCK levels in jejunum were found to change in a similar trend as that in plasma with the concentrations of CCK significantly increased following TBI (99-517% increases) and peaked at 72h.CONCLUSION:Traumatic brain injury can lead to significant changes of brain-gut peptides in both plasma and small intestine, which may be involved in the pathogenesis of complicated gastrointestinal dysfunction.

Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats

AIM: Nuclear factor kappa B (NF-κB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-KB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-κB activation and ICAM-1 expression following TBI. METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-KB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. RESULTS: There was a very low NF-κB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-KB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-κB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-κB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-κB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.

Study of clinical features of amyloid angiopathy hemorrhage and hypertensive intracerebral hemorrhage

Objective: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. Methods: From June 1994 to Oct., 2000, 83 patients admitted to our service with acute intracerebral hemorrhage (ICH) were investigated retrospectively; 41 patients with his-tologically proven diagnosis of cerebral amyloid angiography and 42 patients with clear history of hypertension were investigated. Results: Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74.0 years vs 66.5 years, P<0.05). There was a significantly higher number of hematomas> ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglional hemorrhage was seen in CAA, but in 40.5% in HTN. In CAA-related ICH, su-barachnoid hemorrhage (SAH) was seen in 26 patients (63.4%) compared to only 11 patients (26.2%) in HTN-related ICH. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Typical features of CAA-related ICH included lobar distribution affecting mainly the lobar superficial areas, lobulated appearance, rupture into the subarachnoid space, and secondary IVH from the lobar hemorrhage. More specifically, multiplicity of hemorrhage, bilaterality, and repeated episodes also strongly suggest the diagnosis of CAA. Multiple hemorrhages, defined as 2 or more separate he-matomas in multiple lobes, accounted for 17.1% in CAA-related ICH. Conclusion: There are certain features in CAA on CT and MRI and in clinical settings. To some extent, these features may contribute to distinguishing CAA from HTN related ICH.

U0126 PREVENTS ERK PATHWAY PHOSPHORYLATION AND INTERLEUKIN-1β mRNA PRODUCTION AFTER CEREBRAL ISCHEMIA

Objective To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phos-phorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1βmRNA level was measured by ribonuclease protection assay. Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1βmRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO. Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1βmRNA via the inhibition of ERK pathway.

PROLIFERATION AND DIFFERENTIATION OF NEURAL STEMCELLS IN ADULT RATS AFTER CEREBRAL INFARCTION

Objective To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction. Methods Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine(BrdU), Musashi1, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashi1 were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells. Results Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashi1-positive cells incre-ased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The nu-mber of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats. Conclusion Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.

EFFECT OF PREOPERATIVE USE OF LONG-ACTING OCTREOTIDE ON GROWTH HORMONE SECRETING PITUITARY ADENOMA AND TRANSSPHENOIDAL SURGERY

Objective To investigate whether somatostatin analog octreotide long acting release (LAR) shrinks growth hormone (GH) secreting adenomas, and improves the results of subsequent transsphenoidal surgery. Methods Seventeen previously untreated active acromegalic patients with pituitary adenomas were treated with LAR (30 mg intramuscular injection every 28 days) for 3 months prior to transsphenoidal surgery. Clinical reaction, mean GH secretion, and tumor volume were measured under basal conditions and after LAR treatment. Results Presurgical treatment improved acromegaly symptoms and induced a significant reduction of GH under the 5 ng/mL limit in microadenoma (P < 0.05), while only 18.2% (2/11) in macroadenoma. Meanwhile, tumor shrinkage occurred in 58.8% (10/17) patients, with 1 case in the microadenoma group. All marked shrinkage (> 25%) occurred in the macroadenoma group. Statistical analysis showed tumor shrinkage caused by LAR was greater in macroadenoma group than that in microadenoma group (P < 0.05). During operation, adenoma was soft in 15 cases, with the exception of 2 cases in which the soft tumor was divided by fibrous septa, but all tumor removal was smooth. Conclusions A short term administration of preoperative LAR may induce a significant decrease in GH-secretion level and adenoma volume. Presurgical use of octreotide LAR improves surgical results especially in macroadenomas.

Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases： phase Ⅲ resuIts of the RTOG 9508 randomised trial

BACKGROUND: Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG). METHODS: Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain

PROGNOSTIC FACTORS FOR DEEP SITUATED MALIGNANT GLIOMAS TREATED WITH LINAC RADIOSURGERY

Objective To study the function of radiosurgery on malignant glioma by analyzing prognostic factors affecting malignant gliomas treated with linac radiosurgery. Method Fifty-eight patients with deep situated malignant gliomas, aged 7 to 70 years, 28 anaplastic astrocytomas and 30 glioblastomas multiforme were analyzed. The median volume of tumor was 10.67 cm3, and median prescription dose for linac radiosurgery was 20 Gy. Results were analyzed with Kaplan-Meier curve and Cox regression. Result In follow-up 44.8 percent tumors (26 patients) decreased in size. Median tumor local control interval was 10 months, 15 months for anaplastic astrocytomas, and 9 months for glioblastoma multiforme. Tumor local control probability was 37.9 percent for 1 year and 10.3 percent for 2 years. Median survival was 22.5 months for anaplastic astrocytoma, 13 months for glioblastoma multiforme, and 15 months for all patients. The survival probability was 79.3 percent at 1 year and 20.6 per-cent at 2 years. Isocenter numbers and tumor volume were the prognostic factors for tumor control, but conformity index was the prognostic factor for survival by Cox regression analysis. Considering pathology, only isocenter number and target volume significantly affected tumor control interval. Complications appeared in 44.8 percent patients and the median interval of com-plication onset was 8 months. Symptomatic cerebral edema was observed in 31.0 percent patients. Conclusion Linac radiosurgery can effectively improve tumor local control and prolong survival for deep situated mali-gnant gliomas.

Contribution of spinal glia activation to mechanical hyperalgesia induced by spared nerve injury in rats

Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the three terminal branches of the sciatic nerve of rats (tibial and common peroneal nerves) leaving the sural nerve intact. Continuous intrathe-cal administration of propentofylline, a glial modulating agent, 1 d before and 5 d after operation, was performed to disrupt spinal cord glia function. The vehicle was intrathecally administrated as control. The paw withdrawal threshold to mechanical stimulation (paw withdrawal mechaical threshold PWMT), body mass and motor function were determined pre- and post-surgery. Results: It produced a prolonged mechanical allodynia in the medial and lateral part of the ipsilateral hind paw in SNL models. The treatment with propentofylline significantly prevented the development of mechanical allodynia located in either medial or lateral plantar surface. Rats in two groups showed normal motor function and body weight increase. Conclusion: SNI model can be applied as a useful method with little variance in searching the mechanism of neuropathic pain. These study suggest that spinal glia activation may contribute to mechanical allodynia induced by SNI.

The change of dopamine in cerebrospinal fluid and serum in cats with persistent vegetative state

AIM:To investigate the changes and significance of dopamine(DA) in cerebrospinal fluid and serum in the cats with persistent vegetative state(PVS). METHODS:To measure the level of DA in cerebrospinal fluid and serum with high performance liquid chromatography and electrical chemical detect (HPLC ECD) in the cats with PVS and compared with control group.RESULTS:The level of DA in cerebrospinal fluid and serum in the cats with PVS was obviously lower than that of control group.CONCLUSION:Decrease of DA might be one of important factors of PVS formation.

Hypermethylation of the CPG Island of p16 Gene Correlates with Gene Inactivation in Brain Glioma

Objective:To study the correlation between hypermethylation of the CPG island of p16 gene and its inactivation in gliomas.Mehtods:In 50 cases of brain glioma,immunohistochemical method was applied to detect the expression of p16 protein; PCR a-nalysis was performed to identify the deletion of exons 1,2 of p16 gene and hypermethylation of CPG island of exon 1 of p16 gene in brain glioma.Results:Immunohistochemical analysis showed that p16 protein expression was negative in 27 cases(54%) and positive in 23 cases(46%) of 50 cases of brain gliomas.In the group with negative p16 protein expression(n=27 cases),RT-PCR analysis showed that there were 9 cases(33%) with homozygous deletions ofp16 gene and 7 cases(26%) with hypermethylation of CPG island of p16 gene.Conclusion:The transcriptional inhibition of p16 gene may be induced by aberrant hypermethylation of p16 gene 5'-CPG island in some of the cases without the homozygous deletions of p16 gene.Hypermethylation of 5'-CPG island is one of the important mechanisms for p16 gene inactivation.

Tentorial meningiomas： clinical results in 81 patients treated microsurgically

OBJECTIVE:Even during the microsurgical era, tentorial meningiomas present a formidable surgical challenge when tumor involves critical neurovascular structures. We report our experience with tentorial meningioma with regard to clinical presentation, diagnostic workup, microsurgical technique, complications, and follow-up results. METHODS: In a retrospective study, we reviewed the

5-Aminolevulinic Acid -Mediated Photodynamic Therapy of Human Glioma Cells In Vitro

OBJECTIVE To investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on U251 human glioma cells in vitro.treated with ALA, a typelioma cells were routinely cultured and then of photosensitizer, at various concentrationsfollowed by light irradiation. The PDT-induced phototoxicity of the cells was determined by a MTT assay. In addition, cells were treated with ALA at a fixed concentration and subjected to various doses of light irradiation.RESULTS With the same light dosage (25.0 J/cm^2), the cell survival rates were 70.16%+5.02%, 50.19%+4.79%, 34.97%+5.34%, 27.04%+4.34%, and 24.26% +2.76% at ALA concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 mM,respectively (F =279.88, P =0.0000). But the survival rates of the cells incubated with 2.0 mM ALA compared to those with 4.0 mM ALA (27.04%+4.34% vs 24.26%+2.76%) showed no significant difference (P=0.611). At a single ALA concentration, the cell survival rates were 83.48% + 6.79%,68.09%+6.02%, 33.75%+ 6.70%, 23.34%+ 5.08% and 15.14%+ 3.60% for light doses of 6.25, 12.5, 25.0, 50.0, and 100 J/cm2, respectively (F=422.03,P=0.0000). Without exposure to light, however, the cell survival rates were 96.64% +6.56%, 97.71% +5.48%, 98.10% +6.25%, 99.44% +7.02%, and 95.86% +7.80% for ALA concentrations at 0.25, 0.5, 1.0, 2.0, and 4.0 mM,respectively (F =0.68, P=0.6085). Without ALA in the medium, the cells urvival rates were 98.74% +6.20%, 96.49% +7.13%, 97.60% +5.94%,95.70%+4.86%, 98.08%+6.26% for light doses of 6.25, 12.5, 25.0, 50.0, and 100 J/cm2, respectively (F=0.6400, P=0.6368).CONCLUSION The PDT damage to the U251 cells increased with ALAconcentration within a relative lower range, but then plateaued at higherconcentrations. PDT damage was proportional to the doses of irradiatedlight. Without ALA, the light alone caused no photodynamic damage andALA itself was nontoxic. The ALA-induced PDT appears to be a promisingtherapy for glioma.

Repeated gamma knife radiosurgery for multiple metastatic brain tumours

BACKGROUND:The effectiveness of repeated gamma knife radiosurgery (GKS) for the treatment of multiple metastatic brain turnouts was evaluated. METHODS: This study included 16 patients with 242 tumours, 10 men and 6 women with a mean age of 60.3 years at initial GKS, who underwent GKS four times or more for newly developed metastatic tumours. FINDINGS: Sixteen