The rat 9L gliosarcoma is a widely used syngeneic rat brain tumor model that closely simulates glioblastoma multiforme when implanted in vivo. In this study, we sought to isolate and characterize a subgroup of cancer stem-like cells (CSLCs) from the 9L gliosarcoma cell line, which may represent the tumor-initiating subpopulation of cells. We demonstrate that these CSLCs form clonalderived spheres in media devoid of serum supplemented with the mitogens epidermal growth factor and basic fibroblast growth factor, express the NSC markers Nestin and Sox2, self-renew, and differentiate into neuron-like and glial cells in vitro. More importantly, these cells can propagate and recapitulate tumors when implanted into the brain of syngeneic Fisher rats, and they display a more aggressive course compared with 9L gliosarcoma cells grown in monolayer cultures devoid of mitogens. Furthermore, we compare the chemosensitivity and proliferation rate of 9L gliosarcoma cells grown as a monolayer to those of cells grown as floating spheres and show that the sphere-generated cells have a lower proliferation rate, are more chemoresistant, and express several antiapoptosis and drug-related genes, which may prove to have important clinical implications.

Background and Purpose: A limited number of studies consisting predominantly of ruptured aneurysms have looked at differences in anatomical distribution of aneurysms between male and females. Unlike all other causes of stroke, subarachnoid hemorrhages (SAH) occur more often in women and are thought to be a result of both hormonal influences and variation in wall shear stress. This paper retrospectively looks at a cohort of largely unruptured intracranial aneurysms to determine if there exists a gender discrepancy in the anatomic distribution of cerebral aneurysms. Methods: A retrospective review of consecutive patients with ruptured and unruptured intradural saccular cerebral aneurysms treated endovascularly was performed. Results: Six hundred eighty-two aneurysms were treated. Seventy-two percentage of the patients were women and 27% of patients presented with SAH. Among women, most aneurysms were located along the ICA (54%) while men the ACA (29%, compared to 15% in women), a discrepancy evident in both unruptured and ruptured groups. Females tended to present later in life (59 vs. 55 years), with multiple aneurysms (11 vs. 6% in men), and with SAH (28 vs. 23% in men) – the majority of these ruptured aneurysms were located at the ICA (42%), while men at the ACA (47%). Additionally, the majority (68%) of ruptured ICA aneurysms were PCOM. Conclusion: Understanding the natural history of aneurysms is imperative in treating incidentally found aneurysms. Significant differences exist between the genders in relation to aneurysm location, the most pronounced at the ICA and ACA. Previously described hormonal and hemodynamic theories behind cerebral aneurysm pathogenesis seem like plausible reasons to explain these differences.

Paralleling the rapid development of neuroimaging technology, the introduction of neuronavigation in the 1980s has revolutionized the surgery of intracranial diseases.2,11 Neuronavigation based on CT or MRI studies has tailored surgical interventions to individual anatomy and pathology, with minimal disruption to the physical and functional architecture of the brain. Vascular anatomy is best appreciated with digital subtraction angiography (DSA), which remains the gold standard for imaging of cerebrovascular pathology. Both CT angiography (CTA) and MR angiography (MRA) have lower detection sensitivity and inferior spatial resolution relative to DSA for aneurysms smaller than 3 mm. 1,19,20 The use of DS angiograms as source images for neuronavigation, however, has been limited because DSA studies typically lack the soft-tissue information necessary to register the radiographic image space to the head in the physical space. Images from DSA typically require fusion with CT or MR images for coregistration.Frameless neuronavigation based only on 3D digital subtraction angiography using surface-based facial registration Object. Cerebrovascular lesions can have complicated abnormal anatomy that is not completely characterized by CT or MR angiography. Although 3D rotational angiography provides superior spatial and temporal resolution, catheter angiograms are not easily registered to the patient, limiting the use of these images as a source for neuronavigation. However, 3D digital subtraction angiography (DSA) contains not only vascular anatomy but also facial surface anatomy data. The authors report a novel technique to register 3D DSA images by using only the surface anatomy contained within the data set without having to fuse the DSA image set to other imaging modalities or use fiducial markers.Methods. A cadaver model was first created to assess the accuracy of neuronavigation based on 3D DSA images registered by facial surface anatomy. A 3D DSA scan was obtained of a formalin-fixed cadaver head, with acquisitions of mask and contrast runs. The right common carotid artery was injected prior to the contrast run with a 45% contrast solution diluted with water-soluble red liquid latex. One week later, the head was registered to a neuronavigation system loaded with the 3D DSA images acquired earlier using facial surface anatomy. A right pterional craniotomy was performed and 10 different vascular landmarks were identified and measured for accuracy using the neuronavigation system. Neuronavigation based only on 3D DSA was then used to guide an open clipping procedure for a patient who presented with a ruptured distal lenticulostriate aneurysm.Results. The accuracy of the measurements for the cadaver model was 0.71 ± 0.25 mm (mean ± SE), which is superior to the 1.8-5 mm reported for neuronavigation. The 3D DSA-based navigation-assisted surgery for the distal lenticulostriate aneurysm aided in localization, resulting in a small craniotomy and minimal brain dissection.Conclusions. This is the first example of frameless neu...

Background:Dimethylfumarate (DMF), a drug used in the treatment of psoriasis and multiple sclerosis, has been shown to limit the growth of melanoma cells. The ability of DMF to inhibit the Rel protein has been used to explain the antioncogenic properties of this drug. Studies analyzing the effect of DMF in gliomas are limited. Therefore, we investigated the potential antitumor effects of DMF by assessing its effects on proliferation, cell death, and differentiation in gliomas in several glioma models.Methods:Mouse glioma Gl261, human glioblastoma A172 and human glioblastoma cells from patients were exposed to DMF at therapeutic concentrations (100 μM) and supratherapeutic concentrations (300 μM) and studies to assess proliferation, cellular lysis, and differentiation undertaken. The 5-bromo-2’-deoxyuridine (BRDU) proliferation assay and lactate dehydrogenase LDH cell lysis assay were used. Immunocytochemistry was used to assess differentiation: CD133 (stem cell marker), Nestin (progenitor marker), Sox2 (progenitor marker), β-tubulin III (neuronal marker), glial fibrillary acidic protein (astrocytic marker), and myelin basic protein (oligodendrocytic marker). We also assessed cellular expression of nuclear factor kappa B (NF-κB) via immunocytochemistry.Results:Proliferation significantly decreased and tumor cell lysis significantly increased in all tumor cell lines after exposure to DMF. The human glioblastoma cells expressed the Neuronal Stem Cell marker CD133, Progenitor Cell markers, Neuronal and Astrocytic Cell Markers in vitro. When exposed to DMF, a drastic decline in CD133 expression was observed in addition to a decrease in the expression of NF-κB.Conclusion:DMF appears to have a promising role in the treatment of malignant brain neoplasms. DMF reduced proliferation rate, generated cell lysis, decreased the expression of NF-κB, and restricted the growth of CD133 cells in gliomas. This suggests that DMF may be considered for further antitumor studies, and provide a new treatment modality for brain tumors.

Background:Cerebral metastases are a common neurosurgical finding. Surgery confers several advantages to other therapies, including immediate symptomatic improvement, diagnosis, and relief from corticosteroid dependence. Here we evaluate patients with cerebellar metastases who underwent surgery and compare their findings to those in the literature, and address the benefit of avoiding ventriculo-peritoneal shunting in patients undergoing surgery.Methods:We performed a retrospective analysis involving 50 patients with cerebellar metastases who underwent surgical resection. Ventriculo-peritoneal shunts were placed in patients necessitating permanent CSF drainage. We evaluated presentation, diagnosis, complications, and outcome.Results:Our review included 21 males and 29 females, 29 to 82 years of age. Primary tumors included lung (48%), breast (14%), GI (14%), endometrial/ovarian (6%), melanoma (6%), sarcoma (4%), lymphoma (4%), laryngeal (2%), and other (2%). Clinical symptoms at presentation commonly were those secondary to elevated intracranial pressure and were the initial complaint in 34% of patients. Preoperatively, 29 patients were noted to have hydrocephalus. Importantly, 76% of these patients were able to avoid placement of a ventriculo-peritoneal shunt following surgery. Only two complications were noted in our series of 50 patients, including a symptomatic pseudomeningocele and a wound infection. No symptomatic postoperative hematoma developed in any surgical case.Conclusion:A review of the literature has shown a high complication rate in patients undergoing surgical resection of cerebellar metastases. We have shown that surgical resection of cerebellar metastases is a safe procedure and is effective in the treatment of hydrocephalus in the majority of patients harboring cerebellar lesions.